Summary of recommendations

The guideline recommendations were approved by the Chief Executive Officer of the National Health and Medical Research Council (NHMRC) on 27 October 2017 under section 14A of the National Health and Medical Research Council Act 1992.

In approving the guideline recommendations, NHMRC considers that they meet the NHMRC standard for clinical practice guidelines. This approval is valid for a period of five years.

NHMRC is satisfied that the guideline recommendations are systematically derived, based on the identification and synthesis of the best available scientific evidence, and developed for health professionals practising in an Australian health care setting.

This publication reflects the views of the authors and not necessarily the views of the Australian Government.

This is a summary of the recommendations in these guidelines, numbered according to chapter to which they relate. Please note that some chapters do not have associated recommendations.

This guideline includes evidence-based recommendations (EBR), consensus-based recommendations (CBR) and practice points (PP) as defined in the table below. Recommendations and practice points were developed by working party members and sub-committee members.

Each EBR was assigned a grade by the expert working group, taking into account the volume, consistency, generalisability, applicability and clinical impact of the body of evidence according to NHMRC Level and Grades for Recommendations for Guidelines Developers.

NHMRC approved recommendation types and definitions

Type of recommendation	Definition
Evidence-based recommendation	A recommendation formulated after a systematic review of the evidence, indicating supporting references
Consensus-based recommendation	A recommendation formulated in the absence of quality evidence, after a systematic review of the evidence was conducted and failed to identify admissible evidence on the clinical question
Practice point	A recommendation on a subject that is outside the scope of the search strategy for the systematic review, based on expert opinion and formulated by a consensus process

Source: National Health and Medical Research Council. Procedures and requirements for meeting the NHMRC standard for clinical practice guidelines. Melbourne: National Health and Medical Research Council, 2011

Evidence-based recommendation grades

Grade of recommendation	Description
A	Body of evidence can be trusted to guide practice
B	Body of evidence can be trusted to guide practice in most situations
C	Body of evidence provides some support for recommendation(s) but care should be taken in its application
D	Body of evidence is weak and recommendation must be applied with caution

Source: National Health and Medical Research Council. NHMRC levels of evidence and grades for recommendations for developers of guidelines. Canberra: NHMRC; 2009. (https://www.nhmrc.gov.au/_files_nhmrc/file/guidelines/developers/nhmrc_levels_grades_evidence_120423.pdf)

Recommendations

Primary prevention

Dietary and lifestyle strategies

Practice point
Folic acid intake outside pregnancy should not exceed 1mg per day and those with a history of colorectal adenomas should not take more than 200mcg as a supplement.

• Guidelines:Colorectal cancer/Primary prevention dietary and lifestyle#Practice_point_1
• Folic acid intake outside pregnancy should not exceed 1mg per day and those with a history of colorectal adenomas should not take more than 200mcg as a supplement.
• Good practice point

Practice point
It is recommended to follow the primary prevention messages from the World Cancer Research Fund/American Institute for Cancer Research on tobacco smoking, alcohol, diet, body fatness, physical activity (see Table 2.3).

• Guidelines:Colorectal cancer/Primary prevention dietary and lifestyle#Practice_point_2
• It is recommended to follow the primary prevention messages from the World Cancer Research Fund/American Institute for Cancer Research on tobacco smoking, alcohol, diet, body fatness, physical activity (see Table 2.3).
• Good practice point

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Chemopreventive candidate agents

Evidence-based recommendation

Grade

For all people aged 50–70 years who are at average risk of colorectal cancer, aspirin should be actively considered to prevent colorectal cancer. A low dose (100–300 mg per day) is recommended for at least 2.5 years, commencing at age 50 to 70 years. The benefit may extend to older ages with longer duration of use. Benefit for cancer prevention (though shorter for cardiovascular risk) is evident only 10 years after initiation so a life expectancy of at least 10 years should be taken into consideration in the advice to use aspirin. The choice to take aspirin should be personalised based on age, sex and potential reduction in cardiovascular events, cerebrovascular events and thrombotic stroke. The individual should take into account the potential risks of taking aspirin. Aspirin should be avoided in patients with current dyspepsia, any history of peptic ulcer, aspirin allergy, bleeding diathesis, an increased risk of gastrointestinal haemorrhage (such as associated with use of oral anticoagulants or antiplatelet agents), or renal impairment. The benefit in colorectal cancer risk reduction in women over 65 is less clear cut. However, based on limited data available, older women with cardiovascular risk factors may derive a greater overall benefit than harm.

B

• Clinical question:Aspirin for prevention of colorectal cancer#Recommendation_1
• For all people aged 50–70 years who are at average risk of colorectal cancer, aspirin should be actively considered to prevent colorectal cancer. A low dose (100–300 mg per day) is recommended for at least 2.5 years, commencing at age 50 to 70 years. The benefit may extend to older ages with longer duration of use. Benefit for cancer prevention (though shorter for cardiovascular risk) is evident only 10 years after initiation so a life expectancy of at least 10 years should be taken into consideration in the advice to use aspirin.

The choice to take aspirin should be personalised based on age, sex and potential reduction in cardiovascular events, cerebrovascular events and thrombotic stroke. The individual should take into account the potential risks of taking aspirin. Aspirin should be avoided in patients with current dyspepsia, any history of peptic ulcer, aspirin allergy, bleeding diathesis, an increased risk of gastrointestinal haemorrhage (such as associated with use of oral anticoagulants or antiplatelet agents), or renal impairment.

The benefit in colorectal cancer risk reduction in women over 65 is less clear cut. However, based on limited data available, older women with cardiovascular risk factors may derive a greater overall benefit than harm.

• Recommendation

Practice point
Aspirin should be avoided in patients with uncontrolled hypertension.

• Clinical question:Aspirin for prevention of colorectal cancer#Practice_point_1
• Aspirin should be avoided in patients with uncontrolled hypertension.
• Good practice point

Practice point
Breath testing for Helicobacter pylori (and treatment for those who test positive) can also be considered, as gastrointestinal toxicity from aspirin is enhanced in the presence of Helicobacter pylori.

• Clinical question:Aspirin for prevention of colorectal cancer#Practice_point_2
• Breath testing for Helicobacter pylori (and treatment for those who test positive) can also be considered, as gastrointestinal toxicity from aspirin is enhanced in the presence of Helicobacter pylori.
• Good practice point

Evidence-based recommendation	Grade
People who are at high risk of colorectal cancer due to Lynch Syndrome carrier status should be advised to begin aspirin from the commencement of their colonoscopy screening (usually at age 25 years).	A

• Clinical question:Aspirin for prevention of colorectal cancer#Recommendation_2
• People who are at high risk of colorectal cancer due to Lynch Syndrome carrier status should be advised to begin aspirin from the commencement of their colonoscopy screening (usually at age 25 years).
• Recommendation

Evidence-based recommendation	Grade
Non-syndromic familial cancer patients should be actively considered for aspirin, bearing in mind the possibility of adverse events. 600 mg/day has been shown to be effective, but lower dose (100 mg/day) may be as effective and is recommended based on the data available at the time of the systematic review.	B

• Clinical question:Aspirin for prevention of colorectal cancer#Recommendation_3
• Non-syndromic familial cancer patients should be actively considered for aspirin, bearing in mind the possibility of adverse events.

600 mg/day has been shown to be effective, but lower dose (100 mg/day) may be as effective and is recommended based on the data available at the time of the systematic review.

• Recommendation

Practice point
Where surgery is inappropriate for people with familial adenomatous polyposis, an NSAID (e.g. sulindac) is recommended. (Kim B et al 2011)

• Clinical question:Aspirin for prevention of colorectal cancer#Practice_point_3
• Where surgery is inappropriate for people with familial adenomatous polyposis, an NSAID (e.g. sulindac) is recommended. (Kim B et al 2011)
• Good practice point

Practice point
Without RCT evidence, statins cannot be recommended for chemoprevention at this time.

• Clinical question:Aspirin for prevention of colorectal cancer#Practice_point_4
• Without RCT evidence, statins cannot be recommended for chemoprevention at this time.
• Good practice point

Practice point
Without RCT evidence, metformin cannot be recommended for chemoprevention at this time.

• Clinical question:Aspirin for prevention of colorectal cancer#Practice_point_5
• Without RCT evidence, metformin cannot be recommended for chemoprevention at this time.
• Good practice point

Practice point
Bisphosphonates cannot be recommended for chemoprevention.

• Clinical question:Aspirin for prevention of colorectal cancer#Practice_point_6
• Bisphosphonates cannot be recommended for chemoprevention.
• Good practice point

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Population screening for colorectal cancer

Population screening: Evidence summary and recommendations (PSC1a-d)

Evidence-based recommendation	Grade
Overall population screening strategy The recommended strategy for population screening in Australia, directed at those at average risk of colorectal cancer and without relevant symptoms, is immunochemical faecal occult blood testing every 2 years, starting at age 50 years and continuing to age 74 years.	C

• Guidelines:Colorectal cancer/Population screening recommendations#Recommendation_1
• Overall population screening strategy

The recommended strategy for population screening in Australia, directed at those at average risk of colorectal cancer and without relevant symptoms, is immunochemical faecal occult blood testing every 2 years, starting at age 50 years and continuing to age 74 years.

• Recommendation

Evidence-based recommendation	Grade
Primary screening test An immunochemical faecal occult blood test is recommended as the screening modality for the detection of colorectal cancer in the average-risk population.	C

• Guidelines:Colorectal cancer/Population screening recommendations#Recommendation_2
• Primary screening test

An immunochemical faecal occult blood test is recommended as the screening modality for the detection of colorectal cancer in the average-risk population.

• Recommendation

Evidence-based recommendation	Grade
Primary screening test The emerging faecal, blood or serum tests for cancer-specific biomarkers such as DNA are not recommended as population screening modalities for colorectal cancer.	C

• Guidelines:Colorectal cancer/Population screening recommendations#Recommendation_3
• Primary screening test

The emerging faecal, blood or serum tests for cancer-specific biomarkers such as DNA are not recommended as population screening modalities for colorectal cancer.

• Recommendation

Evidence-based recommendation	Grade
Primary screening test The use of flexible sigmoidoscopy as a primary screening test is not recommended for population screening in the average-risk population.	C

• Guidelines:Colorectal cancer/Population screening recommendations#Recommendation_4
• Primary screening test

The use of flexible sigmoidoscopy as a primary screening test is not recommended for population screening in the average-risk population.

• Recommendation

Evidence-based recommendation	Grade
Frequency of testing Population screening for colorectal cancer using immunochemical faecal blood testing every 2 years is recommended. It is not recommended that the frequency of screening within the NBCSP be increased to yearly.	N/A

• Guidelines:Colorectal cancer/Population screening recommendations#Recommendation_5
• Frequency of testing

Population screening for colorectal cancer using immunochemical faecal blood testing every 2 years is recommended. It is not recommended that the frequency of screening within the NBCSP be increased to yearly.

• Recommendation

Evidence-based recommendation	Grade
Target age group It is recommended that the age range for organised population screening continues to be 50–74 years.	N/A

• Guidelines:Colorectal cancer/Population screening recommendations#Recommendation_6
• Target age group

It is recommended that the age range for organised population screening continues to be 50–74 years.

• Recommendation

Evidence-based recommendation	Grade
Target age group Starting at age 40 is not recommended for population screening as it is unlikely to be cost-effective.	N/A

• Guidelines:Colorectal cancer/Population screening recommendations#Recommendation_7
• Target age group

Starting at age 40 is not recommended for population screening as it is unlikely to be cost-effective.

• Recommendation

Evidence-based recommendation	Grade
Target age group Although modelling indicated that it may be cost-effective, starting screening at age 45 is not recommended for population screening because there is a much less favourable ratio of benefits to harms than for 50–74 years.	N/A

• Guidelines:Colorectal cancer/Population screening recommendations#Recommendation_8
• Target age group

Although modelling indicated that it may be cost-effective, starting screening at age 45 is not recommended for population screening because there is a much less favourable ratio of benefits to harms than for 50–74 years.

• Recommendation

Evidence-based recommendation	Grade
Target age group Extending the age range to 79 or 84 years is not recommended for population screening as it is unlikely to be cost-effective.	N/A

• Guidelines:Colorectal cancer/Population screening recommendations#Recommendation_9
• Target age group

Extending the age range to 79 or 84 years is not recommended for population screening as it is unlikely to be cost-effective.

• Recommendation

Consensus-based recommendation
Resources should be invested in increasing participation in the existing NBCSP target age group of 50–74, rather than by lowering the starting age of screening, to optimise the balance of effectiveness, cost-effectiveness and ratio of benefits to harms.

• Guidelines:Colorectal cancer/Population screening recommendations#Practice_point_1
• Resources should be invested in increasing participation in the existing NBCSP target age group of 50–74, rather than by lowering the starting age of screening, to optimise the balance of effectiveness, cost-effectiveness and ratio of benefits to harms.
• Consensus based recommendation

Consensus-based recommendation
In people aged 45–49 years who request screening after being fully informed of the benefits and harms of testing, general practitioners (GPs) could offer an immunochemical faecal occult blood test every 2 years during the lead-up to the first routine invitation by the NBCSP at age 50 years.

• Guidelines:Colorectal cancer/Population screening recommendations#Practice_point_2
• In people aged 45–49 years who request screening after being fully informed of the benefits and harms of testing, general practitioners (GPs) could offer an immunochemical faecal occult blood test every 2 years during the lead-up to the first routine invitation by the NBCSP at age 50 years.
• Consensus based recommendation

Practice point
Encouragement by GPs and practice staff substantially boosts participation in colorectal cancer screening. Patient endorsement letters in advance of receiving a test kit, the use of GP reminder systems and practice audit are approaches likely to improve participation rates. Increased participation in the NBCSP will increase the program’s effectiveness and cost-effectiveness.

• Guidelines:Colorectal cancer/Population screening recommendations#Practice_point_3
• Encouragement by GPs and practice staff substantially boosts participation in colorectal cancer screening. Patient endorsement letters in advance of receiving a test kit, the use of GP reminder systems and practice audit are approaches likely to improve participation rates. Increased participation in the NBCSP will increase the program’s effectiveness and cost-effectiveness.
• Good practice point

Practice point
GPs have a critically important role in managing the interface between population screening and personalised care. This role includes identifying and advising those who should opt off the NBCSP because of the presence of major comorbidities and limited life expectancy and those who should defer participation for several months because of recent surgery or major illness.

• Guidelines:Colorectal cancer/Population screening recommendations#Practice_point_4
• GPs have a critically important role in managing the interface between population screening and personalised care. This role includes identifying and advising those who should opt off the NBCSP because of the presence of major comorbidities and limited life expectancy and those who should defer participation for several months because of recent surgery or major illness.
• Good practice point

Practice point

Participation in a population screening program is not recommended for people with symptoms such as rectal bleeding or persistent change in bowel habit or with iron-deficiency anaemia, nor for those who should be having regular surveillance or screening based on colonoscopy, e.g. for past colorectal cancer or adenoma, chronic inflammatory bowel disease, a strong family history of colorectal cancer, or a high-risk genetic cancer syndrome (see Risk and screening based on family history of colorectal cancer).

• Guidelines:Colorectal cancer/Population screening recommendations#Practice_point_5
• Participation in a population screening program is not recommended for people with symptoms such as rectal bleeding or persistent change in bowel habit or with iron-deficiency anaemia, nor for those who should be having regular surveillance or screening based on colonoscopy, e.g. for past colorectal cancer or adenoma, chronic inflammatory bowel disease, a strong family history of colorectal cancer, or a high-risk genetic cancer syndrome (see Risk and screening based on family history of colorectal cancer).
• Good practice point

Practice point
Individuals who have had a high-quality colonoscopy performed within the previous two years should allow another two years to elapse (i.e. skip a round) before participating in their next round of iFOBT screening. Colorectal cancer will rarely be present within that interval. High-quality colonoscopy is defined in the Clinical Practice Guidelines for Surveillance Colonoscopy.

• Guidelines:Colorectal cancer/Population screening recommendations#Practice_point_6
• Individuals who have had a high-quality colonoscopy performed within the previous two years should allow another two years to elapse (i.e. skip a round) before participating in their next round of iFOBT screening. Colorectal cancer will rarely be present within that interval.

High-quality colonoscopy is defined in the Clinical Practice Guidelines for Surveillance Colonoscopy.

• Good practice point

Practice point
GPs have a key role in advising patients who are at average or slightly above average risk that iFOBT is the preferred method of screening. They should discuss the relative harms and benefits of colonoscopy and discourage inappropriate use of colonoscopy as a screening method.

• Guidelines:Colorectal cancer/Population screening recommendations#Practice_point_7
• GPs have a key role in advising patients who are at average or slightly above average risk that iFOBT is the preferred method of screening. They should discuss the relative harms and benefits of colonoscopy and discourage inappropriate use of colonoscopy as a screening method.
• Good practice point

Practice point

Participants with positive iFOBT results should have follow-up investigation unless there was a clear breach in protocol when samples were collected (e.g. menstrual blood loss close to the time of sample collection). Repeating the iFOBT test after a positive result carries the risk of a falsely negative test result on the second occasion because of low levels of bleeding from a cancer or adenoma, intermittent bleeding, or uneven distribution of blood in the stools.

• Guidelines:Colorectal cancer/Population screening recommendations#Practice_point_8
• Participants with positive iFOBT results should have follow-up investigation unless there was a clear breach in protocol when samples were collected (e.g. menstrual blood loss close to the time of sample collection). Repeating the iFOBT test after a positive result carries the risk of a falsely negative test result on the second occasion because of low levels of bleeding from a cancer or adenoma, intermittent bleeding, or uneven distribution of blood in the stools.
• Good practice point

Practice point
Colonoscopy should be performed as promptly as possible after a positive iFOBT to minimise the risk of psychological harm, although there is no evidence that prognosis is worsened within 120 days if cancer is present.

• Guidelines:Colorectal cancer/Population screening recommendations#Practice_point_9
• Colonoscopy should be performed as promptly as possible after a positive iFOBT to minimise the risk of psychological harm, although there is no evidence that prognosis is worsened within 120 days if cancer is present.
• Good practice point

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The symptomatic patient

Signs and symptoms predictive of colorectal cancer

Evidence-based recommendation	Grade
The urgency of colonoscopy to investigate symptoms suggestive of colorectal cancer should be based on an assessment of patient age, symptom profile and results of simple investigations including full blood count, iron studies and iFOBT (see Table 10.1 for consensus-based colonoscopy triage categories).	C

• Clinical question:Symptoms predictive of colorectal cancer#Recommendation_1
• The urgency of colonoscopy to investigate symptoms suggestive of colorectal cancer should be based on an assessment of patient age, symptom profile and results of simple investigations including full blood count, iron studies and iFOBT (see Table 10.1 for consensus-based colonoscopy triage categories).
• Recommendation

Consensus-based recommendation
In people with symptoms other than overt rectal bleeding, immunochemical faecal occult blood testing (iFOBT) can be used as part of the diagnostic assessment in primary care.

• Clinical question:Symptoms predictive of colorectal cancer#Practice_point_1
• In people with symptoms other than overt rectal bleeding, immunochemical faecal occult blood testing (iFOBT) can be used as part of the diagnostic assessment in primary care.
• Consensus based recommendation

Practice point
Immunochemical faecal occult blood testing (iFOBT) is of particular use in the following circumstances to support diagnostic assessment and inform urgency of colonoscopy: people over 50 years with either unexplained weight loss or abdominal pain people under 60 years with either altered bowel habit or anaemia.

• Clinical question:Symptoms predictive of colorectal cancer#Practice_point_2
• Immunochemical faecal occult blood testing (iFOBT) is of particular use in the following circumstances to support diagnostic assessment and inform urgency of colonoscopy:
• people over 50 years with either unexplained weight loss or abdominal pain
• people under 60 years with either altered bowel habit or anaemia.
• Good practice point

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Optimal maximum time from referral to diagnosis and treatment

Evidence-based recommendation

Grade

For patients with symptoms suggestive of colorectal cancer, the total time from first healthcare presentation† to diagnostic colonoscopy should be no more than 120 days. Diagnostic intervals greater than 120 days are associated with poorer clinical outcomes. † First healthcare presentation is defined as the date of presentation in general practice with symptoms suggestive of colorectal cancer or positive iFOBT for screening.

C

• Clinical question:Diagnosis interval in colorectal cancer#Recommendation_1
• For patients with symptoms suggestive of colorectal cancer, the total time from first healthcare presentation^† to diagnostic colonoscopy should be no more than 120 days. Diagnostic intervals greater than 120 days are associated with poorer clinical outcomes.

^† First healthcare presentation is defined as the date of presentation in general practice with symptoms suggestive of colorectal cancer or positive iFOBT for screening.

• Recommendation

Evidence-based recommendation

Grade

A diagnostic interval of 120 days should be the maximum time from first healthcare presentation† to diagnostic colonoscopy for triage Categories 1 and 2, whether it is for a patient with symptoms or after a positive iFOBT used for colorectal cancer screening. Diagnostic intervals greater than 120 days are associated with poorer clinical outcomes. † First healthcare presentation is defined as the date of presentation in general practice with symptoms suggestive of colorectal cancer or positive iFOBT for screening.

D

• Clinical question:Diagnosis interval in colorectal cancer#Recommendation_2
• A diagnostic interval of 120 days should be the maximum time from first healthcare presentation^† to diagnostic colonoscopy for triage Categories 1 and 2, whether it is for a patient with symptoms or after a positive iFOBT used for colorectal cancer screening. Diagnostic intervals greater than 120 days are associated with poorer clinical outcomes.

^† First healthcare presentation is defined as the date of presentation in general practice with symptoms suggestive of colorectal cancer or positive iFOBT for screening.

• Recommendation

Consensus-based recommendation
Triage category 1 patients, whether due to symptoms or positive iFOBT, should continue to be considered most urgent and prioritised for diagnostic colonoscopy, in any model of care at any jurisdictional level.

• Clinical question:Diagnosis interval in colorectal cancer#Practice_point_1
• Triage category 1 patients, whether due to symptoms or positive iFOBT, should continue to be considered most urgent and prioritised for diagnostic colonoscopy, in any model of care at any jurisdictional level.
• Consensus based recommendation

Practice point

Colonoscopy for symptomatic patients should be performed as promptly as possible after referral from general practice, especially for those meeting triage Category 1 criteria. If cancer is present, there is no evidence that prognosis is worsened within 120 days from first presentation to diagnostic colonoscopy. However, performing colonoscopy as promptly as possible after referral from general practice is to minimise the risk of psychological harm in symptomatic or iFOBT-positive patients who are potentially anxious while awaiting investigation. Prompt scheduling will also help to ensure that any unexpected delays between general practice referral and colonoscopy triaging do not flow on to exceed the 120-day threshold after which prognosis can worsen if cancer is present.

• Clinical question:Diagnosis interval in colorectal cancer#Practice_point_2
• Colonoscopy for symptomatic patients should be performed as promptly as possible after referral from general practice, especially for those meeting triage Category 1 criteria. If cancer is present, there is no evidence that prognosis is worsened within 120 days from first presentation to diagnostic colonoscopy. However, performing colonoscopy as promptly as possible after referral from general practice is to minimise the risk of psychological harm in symptomatic or iFOBT-positive patients who are potentially anxious while awaiting investigation. Prompt scheduling will also help to ensure that any unexpected delays between general practice referral and colonoscopy triaging do not flow on to exceed the 120-day threshold after which prognosis can worsen if cancer is present.
• Good practice point

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Risk and screening based on family history

Colorectal cancer risk according to family history

Evidence-based recommendation	Grade
Category 1 People who have one relative with colorectal cancer diagnosed at age 55 or older should be advised that their own risk of developing colorectal cancer could be up to twice the average risk, but is still not high enough to justify CRC screening by colonoscopy.	C

• Clinical question:Family history and CRC risk#Recommendation_1
• Category 1

People who have one relative with colorectal cancer diagnosed at age 55 or older should be advised that their own risk of developing colorectal cancer could be up to twice the average risk, but is still not high enough to justify CRC screening by colonoscopy.

• Recommendation

Evidence-based recommendation

Grade

Category 2 People should be advised that their risk of developing colorectal cancer is at least three times higher than average, but could be up to six times higher than average, if they have any of the following: one first-degree relative with colorectal cancer diagnosed before age 55 years two first-degree relatives with colorectal cancer diagnosed at any age one first-degree relative and at least two second-degree relative diagnosed with colorectal cancer at any age.

C

• Clinical question:Family history and CRC risk#Recommendation_2
• Category 2

People should be advised that their risk of developing colorectal cancer is at least three times higher than average, but could be up to six times higher than average, if they have any of the following:

• one first-degree relative with colorectal cancer diagnosed before age 55 years
• two first-degree relatives with colorectal cancer diagnosed at any age
• one first-degree relative and at least two second-degree relative diagnosed with colorectal cancer at any age.
• Recommendation

Evidence-based recommendation

Grade

Category 3 People should be advised that their risk of colorectal cancer is at least seven times higher than average, but could be up to 10 times higher than average, if they have either of the following: at least three first-degree or second-degree relatives with colorectal cancer, with at least one diagnosed before age 55 years at least three first-degree relatives with colorectal cancer diagnosed at any age.

C

• Clinical question:Family history and CRC risk#Recommendation_3
• Category 3

People should be advised that their risk of colorectal cancer is at least seven times higher than average, but could be up to 10 times higher than average, if they have either of the following:

• at least three first-degree or second-degree relatives with colorectal cancer, with at least one diagnosed before age 55 years
• at least three first-degree relatives with colorectal cancer diagnosed at any age.
• Recommendation

Practice point
Approximately 95-98% of the population are in Category 1 (near average risk of developing colorectal cancer).

• Clinical question:Family history and CRC risk#Practice_point_1
• Approximately 95-98% of the population are in Category 1 (near average risk of developing colorectal cancer).
• Good practice point

Practice point
Approximately 65% of those with a family history of colorectal cancer only have a weak family history which means they are category 1 risk.

• Clinical question:Family history and CRC risk#Practice_point_2
• Approximately 65% of those with a family history of colorectal cancer only have a weak family history which means they are category 1 risk.
• Good practice point

Practice point

Medical information that patients provide about their relatives is often inaccurate. (St John et al 1993, Love et al 1985, Douglas et al 1999, Ruo et al 2001, Mitchell et al 2004) The percentage of colorectal cancer reports that are correct (positive predictive value) is 86% meaning that reports by relatives are usually true. However, a high proportion of people appear to be unaware that their relatives have had colorectal cancer, with the percentage of all colorectal cancers in first-degree relatives that are reported (sensitivity) being 27%. (Mai 2011).

• Clinical question:Family history and CRC risk#Practice_point_3
• Medical information that patients provide about their relatives is often inaccurate. (St John et al 1993, Love et al 1985, Douglas et al 1999, Ruo et al 2001, Mitchell et al 2004) The percentage of colorectal cancer reports that are correct (positive predictive value) is 86% meaning that reports by relatives are usually true. However, a high proportion of people appear to be unaware that their relatives have had colorectal cancer, with the percentage of all colorectal cancers in first-degree relatives that are reported (sensitivity) being 27%. (Mai 2011).
• Good practice point

Practice point
Given the potential importance of an accurate risk prediction for an individual, every effort should be made to collect reliable information.

• Clinical question:Family history and CRC risk#Practice_point_4
• Given the potential importance of an accurate risk prediction for an individual, every effort should be made to collect reliable information.
• Good practice point

Practice point
When there is uncertainty on family history, people should be encouraged to seek clarification within their family including details on which relatives have had colorectal cancer and their ages of diagnoses.

• Clinical question:Family history and CRC risk#Practice_point_5
• When there is uncertainty on family history, people should be encouraged to seek clarification within their family including details on which relatives have had colorectal cancer and their ages of diagnoses.
• Good practice point

Practice point
If a family medical history appears to be significant but diagnoses prove difficult to confirm, it may be appropriate to seek expert help from a familial cancer clinic who have resources available to confirm cancer diagnoses.

• Clinical question:Family history and CRC risk#Practice_point_6
• If a family medical history appears to be significant but diagnoses prove difficult to confirm, it may be appropriate to seek expert help from a familial cancer clinic who have resources available to confirm cancer diagnoses.
• Good practice point

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Screening strategies for people with a family history of colorectal cancer

Practice point
For people with category 1 risk of colorectal cancer with one relative with colorectal cancer, iFOBT should be considered every 2 years from age 45, given the risk of colorectal cancer at this age is approximately equivalent to the population risk at age 50.

• Guidelines:Colorectal cancer/Screening based on family history#Practice_point_1
• For people with category 1 risk of colorectal cancer with one relative with colorectal cancer, iFOBT should be considered every 2 years from age 45, given the risk of colorectal cancer at this age is approximately equivalent to the population risk at age 50.
• Good practice point

Practice point
For people with category 2 risk of colorectal cancer: iFOBT should be performed every 2 years from age 40 up to age 50, and colonoscopy should be performed every 5 years from age 50 to age 74. low-dose (100 mg) aspirin daily should be considered (see Aspirin).

• Guidelines:Colorectal cancer/Screening based on family history#Practice_point_2
• For people with category 2 risk of colorectal cancer:
• iFOBT should be performed every 2 years from age 40 up to age 50, and colonoscopy should be performed every 5 years from age 50 to age 74.
• low-dose (100 mg) aspirin daily should be considered (see Aspirin).
• Good practice point

Practice point
For people in category 2, CT colonography can be offered if colonoscopy is contraindicated (Dachman 2003).

• Guidelines:Colorectal cancer/Screening based on family history#Practice_point_3
• For people in category 2, CT colonography can be offered if colonoscopy is contraindicated (Dachman 2003).
• Good practice point

Practice point
Because of the possibility of Lynch syndrome, a complete family history should be taken and updated regularly, and the accuracy of the cancer diagnoses and polyp pathology should be checked carefully.

• Guidelines:Colorectal cancer/Screening based on family history#Practice_point_4
• Because of the possibility of Lynch syndrome, a complete family history should be taken and updated regularly, and the accuracy of the cancer diagnoses and polyp pathology should be checked carefully.
• Good practice point

Practice point
Category 2 can now be met by inclusion of relatives from both sides of the family. Genetic testing is not appropriate at present for people with category 2 risk. Tumour testing for Lynch syndrome-related changes, using immunohistochemistry and microsatellite instability, should be considered when any of the revised Bethesda criteria are met (see Lynch syndrome).

• Guidelines:Colorectal cancer/Screening based on family history#Practice_point_5
• Category 2 can now be met by inclusion of relatives from both sides of the family. Genetic testing is not appropriate at present for people with category 2 risk. Tumour testing for Lynch syndrome-related changes, using immunohistochemistry and microsatellite instability, should be considered when any of the revised Bethesda criteria are met (see Lynch syndrome).
• Good practice point

Practice point
As with all forms of screening, those at risk should be carefully checked for the presence of symptoms that might be due to colorectal neoplasia. Where symptoms are present, appropriate diagnostic steps should be taken before entry into a screening program.

• Guidelines:Colorectal cancer/Screening based on family history#Practice_point_6
• As with all forms of screening, those at risk should be carefully checked for the presence of symptoms that might be due to colorectal neoplasia. Where symptoms are present, appropriate diagnostic steps should be taken before entry into a screening program.
• Good practice point

Practice point

For people with category 3 risk of colorectal cancer: iFOBT should be performed every 2 years from age 35 up to age 45, then 5-yearly colonoscopy from age 45 to age 74. Low-dose (100 mg) aspirin daily should be considered (see Aspirin). Referral to a genetic centre for hereditary cancer syndromes should be considered. Those carrying their family-specific mutation or having uncertain genetic status require careful cancer screening (see High-risk familial syndromes).

• Guidelines:Colorectal cancer/Screening based on family history#Practice_point_7
• For people with category 3 risk of colorectal cancer:
• iFOBT should be performed every 2 years from age 35 up to age 45, then 5-yearly colonoscopy from age 45 to age 74.
• Low-dose (100 mg) aspirin daily should be considered (see Aspirin).
• Referral to a genetic centre for hereditary cancer syndromes should be considered. Those carrying their family-specific mutation or having uncertain genetic status require careful cancer screening (see High-risk familial syndromes).
• Good practice point

Practice point
Category 3 can now be met by inclusion of relatives from both sides of the family. This is expected to increase the numbers in this category by approximately 50%. Referral to a genetic centre for hereditary cancer syndromes should be prioritised to those with family members with colorectal cancer from the same side of the family.

• Guidelines:Colorectal cancer/Screening based on family history#Practice_point_8
• Category 3 can now be met by inclusion of relatives from both sides of the family. This is expected to increase the numbers in this category by approximately 50%. Referral to a genetic centre for hereditary cancer syndromes should be prioritised to those with family members with colorectal cancer from the same side of the family.
• Good practice point

Practice point
Screening recommendations no longer specify that screening should begin at 10 years younger than the age of first diagnosis of colorectal cancer in the family, as there is no published evidence to support this strategy.

• Guidelines:Colorectal cancer/Screening based on family history#Practice_point_9
• Screening recommendations no longer specify that screening should begin at 10 years younger than the age of first diagnosis of colorectal cancer in the family, as there is no published evidence to support this strategy.
• Good practice point

Evidence-based recommendation	Grade
Category 1 For people with a family history of colorectal cancer who are assessed as having category 1 risk, iFOBT should be performed every 2 years from age 50 to age 74. See Population screening for colorectal cancer. For those with one first-degree relative with colorectal cancer, iFOBT every two years from age 45 should be considered.	C

• Guidelines:Colorectal cancer/Screening based on family history#Recommendation_1
• Category 1

For people with a family history of colorectal cancer who are assessed as having category 1 risk, iFOBT should be performed every 2 years from age 50 to age 74.

See Population screening for colorectal cancer.

For those with one first-degree relative with colorectal cancer, iFOBT every two years from age 45 should be considered.

• Recommendation

Evidence-based recommendation	Grade
Category 2 For category 2 patients, offer iFOBT every 2 years starting at age 40, then colonoscopy every 5 years starting at age 50. CT colonography may be offered if colonoscopy is contraindicated.	C

• Guidelines:Colorectal cancer/Screening based on family history#Recommendation_2
• Category 2

For category 2 patients, offer iFOBT every 2 years starting at age 40, then colonoscopy every 5 years starting at age 50. CT colonography may be offered if colonoscopy is contraindicated.

• Recommendation

Evidence-based recommendation	Grade
Category 3 For category 3 patients, offer iFOBT every two years starting at age 35, then colonoscopy every five years starting at age 45. CT colonography may be offered if colonoscopy is contraindicated.	C

• Guidelines:Colorectal cancer/Screening based on family history#Recommendation_3
• Category 3

For category 3 patients, offer iFOBT every two years starting at age 35, then colonoscopy every five years starting at age 45. CT colonography may be offered if colonoscopy is contraindicated.

• Recommendation

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High-risk familial syndromes

Familial adenomatous polyposis (FAP)

Practice point

Colonic surveillance should be offered to: individuals found on genetic testing to carry a pathogenic APC mutation first-degree relatives of patients with FAP or AFAP in whom genetic testing has been declined or is not possible because the family mutation has not been identified. Surveillance should commence from age 10 to 15 years or earlier if there are gastrointestinal symptoms (Robays and Poppe, 2014). In families with classical FAP, flexible sigmoidoscopy is adequate since adenomas occur simultaneously throughout the colorectum (Syngal et al., 2015; Stoffel et al., 2015; Robays and Poppe, 2014). Once an adenoma is identified, annual colonoscopy should be performed until colectomy is undertaken. In AFAP, surveillance should be by colonoscopy since the first adenomas may only be present in the proximal colon but surveillance can be delayed until 18 years of age (Syngal et al., 2015; Cancer Institute NSW 2016; Robays and Poppe, 2014).

• Guidelines:Colorectal cancer/Familial adenomatous polyposis#Practice_point_1
• * Colonic surveillance should be offered to:

• individuals found on genetic testing to carry a pathogenic APC mutation
• first-degree relatives of patients with FAP or AFAP in whom genetic testing has been declined or is not possible because the family mutation has not been identified.

Surveillance should commence from age 10 to 15 years or earlier if there are gastrointestinal symptoms (Robays and Poppe, 2014). In families with classical FAP, flexible sigmoidoscopy is adequate since adenomas occur simultaneously throughout the colorectum (Syngal et al., 2015; Stoffel et al., 2015; Robays and Poppe, 2014). Once an adenoma is identified, annual colonoscopy should be performed until colectomy is undertaken. In AFAP, surveillance should be by colonoscopy since the first adenomas may only be present in the proximal colon but surveillance can be delayed until 18 years of age (Syngal et al., 2015; Cancer Institute NSW 2016; Robays and Poppe, 2014).

• Good practice point

Practice point

Total colectomy and ileorectal anastomosis should be reserved for patients with rectal adenomas considered easily controllable by endoscopy and < 1000 colonic adenomas. Proctocolectomy with a permanent ileostomy is rarely needed (Syngal et al., 2015). Annual surveillance of the residual rectum or ileal pouch is required following colectomy (Cancer Institute NSW 2016). Some patients with AFAP can be managed with colonoscopic polypectomy at one- to two-yearly intervals (Syngal et al., 2015; Balmaña et al., 2013). If surgery is required due to a high number of adenomas, colectomy with ileorectal anastomosis can nearly always be performed, because of the small number of adenomas in the rectum (Syngal et al., 2015; Balmaña et al., 2013)

• Guidelines:Colorectal cancer/Familial adenomatous polyposis#Practice_point_2
• *Total colectomy and ileorectal anastomosis should be reserved for patients with rectal adenomas considered easily controllable by endoscopy and < 1000 colonic adenomas. Proctocolectomy with a permanent ileostomy is rarely needed (Syngal et al., 2015). Annual surveillance of the residual rectum or ileal pouch is required following colectomy (Cancer Institute NSW 2016).

• Some patients with AFAP can be managed with colonoscopic polypectomy at one- to two-yearly intervals (Syngal et al., 2015; Balmaña et al., 2013). If surgery is required due to a high number of adenomas, colectomy with ileorectal anastomosis can nearly always be performed, because of the small number of adenomas in the rectum (Syngal et al., 2015; Balmaña et al., 2013)
• Good practice point

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MUTYH-associated polyposis

Practice point

Referral to a genetics service for germline genetic testing for mutations in MUTYH is indicated for persons with a cumulative count of ≥ 20 colorectal adenomas at any age (Syngal et al., 2015). It is also indicated for siblings of a MUTYH biallelic mutation carrier (Syngal et al., 2015). Testing may also be considered in patients with ≥ 10 adenomas and any of the following (Syngal et al., 2015) : age under 50 synchronous colorectal cancer both adenomatous and serrated polyps where the adenomatous polyps dominate family history suggestive of recessive inheritance (e.g. consanguinity in parents or siblings with documented adenomatous polyposis or colorectal cancer). Clinical practice in some familial cancer clinics would accept patients in these categories even if there are no synchronous adenomas in the proband.

• Guidelines:Colorectal cancer/MUTYH associated polyposis#Practice_point_1
• *Referral to a genetics service for germline genetic testing for mutations in MUTYH is indicated for persons with a cumulative count of ≥ 20 colorectal adenomas at any age (Syngal et al., 2015). It is also indicated for siblings of a MUTYH biallelic mutation carrier (Syngal et al., 2015).

Testing may also be considered in patients with ≥ 10 adenomas and any of the following (Syngal et al., 2015) :

• age under 50
• synchronous colorectal cancer
• both adenomatous and serrated polyps where the adenomatous polyps dominate
• family history suggestive of recessive inheritance (e.g. consanguinity in parents or siblings with documented adenomatous polyposis or colorectal cancer).

Clinical practice in some familial cancer clinics would accept patients in these categories even if there are no synchronous adenomas in the proband.

• Good practice point

Practice point

Biallelic mutation carriers should have colonoscopy every 2 years starting at age 18 to 20 years(Cancer Institute NSW, 2016; Robays and Poppe, 2014; Balmaña et al., 2013). If polyps are detected, annual colonoscopy may be required to control the polyp burden (Cancer Institute NSW, 2016). If polyps cannot be easily managed colonoscopically, a colectomy with ileorectal anastomosis should be considered and discussed with the patient (Cancer Institute NSW, 2016; Balmaña et al., 2013) The residual rectum requires annual surveillance.

• Guidelines:Colorectal cancer/MUTYH associated polyposis#Practice_point_2
• Biallelic mutation carriers should have colonoscopy every 2 years starting at age 18 to 20 years(Cancer Institute NSW, 2016; Robays and Poppe, 2014; Balmaña et al., 2013). If polyps are detected, annual colonoscopy may be required to control the polyp burden (Cancer Institute NSW, 2016). If polyps cannot be easily managed colonoscopically, a colectomy with ileorectal anastomosis should be considered and discussed with the patient (Cancer Institute NSW, 2016; Balmaña et al., 2013) The residual rectum requires annual surveillance.
• Good practice point

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Lynch syndrome

Practice point
All colorectal cancers should be tested for mismatch repair deficiency as a means to subsequently identify Lynch syndrome (Robays and Poppe, 2014; Ladabaum et al., 2015; Giardiello et al., 2014; Rubenstein et al., 2015).

• Guidelines:Colorectal cancer/Lynch syndrome#Practice_point_1
• *All colorectal cancers should be tested for mismatch repair deficiency as a means to subsequently identify Lynch syndrome (Robays and Poppe, 2014; Ladabaum et al., 2015; Giardiello et al., 2014; Rubenstein et al., 2015).
• Good practice point

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Juvenile polyposis syndrome

Practice point
In patients with a diagnosis of juvenile polyposis syndrome, colonoscopy should commence at age 12–15 or earlier if symptoms occur (Syngal et al., 2015; Cancer Institute NSW, 2016). It should be repeated every 1 to 3 years depending on polyp burden. Colectomy is indicated if polyps cannot be managed endoscopically (Syngal et al., 2015; Cancer Institute NSW, 2016).

• Guidelines:Colorectal cancer/Juvenile polyposis syndrome#Practice_point_1
• In patients with a diagnosis of juvenile polyposis syndrome, colonoscopy should commence at age 12–15 or earlier if symptoms occur (Syngal et al., 2015; Cancer Institute NSW, 2016). It should be repeated every 1 to 3 years depending on polyp burden. Colectomy is indicated if polyps cannot be managed endoscopically (Syngal et al., 2015; Cancer Institute NSW, 2016).
• Good practice point

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Serrated polyposis syndrome

Practice point
Expert opinion is that colonoscopy should be performed every 1 to 3 years with the aim to remove all polyps ≥ 5mm. If the number and size of polyps make it impossible to achieve this, colectomy and ileorectal anastomosis should be considered.(Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW, et al 2015)(Cancer Institute NSW 2016)

• Guidelines:Colorectal cancer/Serrated polyposis syndrome#Practice_point_1
• Expert opinion is that colonoscopy should be performed every 1 to 3 years with the aim to remove all polyps ≥ 5mm. If the number and size of polyps make it impossible to achieve this, colectomy and ileorectal anastomosis should be considered.(Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW, et al 2015)(Cancer Institute NSW 2016)
• Good practice point

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Imaging a patient with a diagnosis of colon/rectal adenocarcinoma

Imaging for colon cancer

Practice point
CT colonoscopy should be considered for a patient with colon cancer if it has not been possible to view the entire colon by colonoscopy due to the risk of synchronous tumours. (New Zealand Guidelines Group 2011.)

• Guidelines:Colorectal cancer/Imaging colon cancer#Practice_point_1
• CT colonoscopy should be considered for a patient with colon cancer if it has not been possible to view the entire colon by colonoscopy due to the risk of synchronous tumours. (New Zealand Guidelines Group 2011.)
• Good practice point

Practice point
If CT shows metastatic disease confined to the liver, MRI of the liver can be considered to assess for resectability, particularly if the background liver parenchyma is abnormal, the patient has recently received chemotherapy, or when a patient cannot have iodinated contrast.

• Guidelines:Colorectal cancer/Imaging colon cancer#Practice_point_2
• If CT shows metastatic disease confined to the liver, MRI of the liver can be considered to assess for resectability, particularly if the background liver parenchyma is abnormal, the patient has recently received chemotherapy, or when a patient cannot have iodinated contrast.
• Good practice point

Practice point
For patients with colorectal cancer who have potentially resectable metastatic disease, PET-CT is recommended to detect additional metastases.

• Guidelines:Colorectal cancer/Imaging colon cancer#Practice_point_3
• For patients with colorectal cancer who have potentially resectable metastatic disease, PET-CT is recommended to detect additional metastases.
• Good practice point

Practice point
For patients with stage II and III disease who have undergone initial surgery and/or adjuvant treatment, a suitable approach to imaging surveillance may involve 12-monthly CT of chest, abdomen and pelvis.

• Guidelines:Colorectal cancer/Imaging colon cancer#Practice_point_4
• For patients with stage II and III disease who have undergone initial surgery and/or adjuvant treatment, a suitable approach to imaging surveillance may involve 12-monthly CT of chest, abdomen and pelvis.
• Good practice point

Practice point
For patients with stage IV disease who have undergone a resection procedure with curative intent, a suitable approach to imaging surveillance may involve CT of chest, abdomen and pelvis every 6 months.

• Guidelines:Colorectal cancer/Imaging colon cancer#Practice_point_5
• For patients with stage IV disease who have undergone a resection procedure with curative intent, a suitable approach to imaging surveillance may involve CT of chest, abdomen and pelvis every 6 months.
• Good practice point

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Imaging for rectal cancer

Practice point
MRI of the rectum is the recommended staging investigation for rectal cancer.

• Guidelines:Colorectal cancer/Imaging rectal cancer#Practice_point_1
• MRI of the rectum is the recommended staging investigation for rectal cancer.
• Good practice point

Practice point
High-resolution sequences must be performed and must meet accepted criteria.

• Guidelines:Colorectal cancer/Imaging rectal cancer#Practice_point_2
• High-resolution sequences must be performed and must meet accepted criteria.
• Good practice point

Practice point
Additional sequences coronal to the anal canal are required for low tumours (Table 7.2).

• Guidelines:Colorectal cancer/Imaging rectal cancer#Practice_point_3
• Additional sequences coronal to the anal canal are required for low tumours (Table 7.2).
• Good practice point

Practice point
Template reports are recommended, which include all of: Distance from anal verge (and puborectalis sling for low tumours) Relationship to the peritoneal reflection T stage including spread in mm beyond muscularis N stage and pelvic lymph nodes using morphological criteria EMVI status CRM status using 1mm as a cut-off distance.

• Guidelines:Colorectal cancer/Imaging rectal cancer#Practice_point_4
• Template reports are recommended, which include all of:
• Distance from anal verge (and puborectalis sling for low tumours)
• Relationship to the peritoneal reflection
• T stage including spread in mm beyond muscularis
• N stage and pelvic lymph nodes using morphological criteria
• EMVI status
• CRM status using 1mm as a cut-off distance.
• Good practice point

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Pathlogy and staging

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Selection of a clinicopathological staging system

Practice point
TNM staging, ACPS/Concord staging and the data required to stage the patient should all be recorded to allow national and international comparisons.

• Guidelines:Colorectal cancer/Selection of a clinicopathological staging system#Practice_point_1
• TNM staging, ACPS/Concord staging and the data required to stage the patient should all be recorded to allow national and international comparisons.
• Good practice point

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Additional information on pathology reporting

Practice point
DNA mismatch repair status studies should be performed on all cases of colorectal cancer for the detection of Lynch syndrome.

• Guidelines:Colorectal cancer/Additional information pathology reporting#Practice_point_1
• DNA mismatch repair status studies should be performed on all cases of colorectal cancer for the detection of Lynch syndrome.
• Good practice point

Practice point
BRAF mutation studies should be performed in conjunction with DNA mismatch repair status studies to differentiate between sporadic and familial (Lynch syndrome) cases of DNA mismatch repair status-deficient colorectal cancer.

• Guidelines:Colorectal cancer/Additional information pathology reporting#Practice_point_2
• BRAF mutation studies should be performed in conjunction with DNA mismatch repair status studies to differentiate between sporadic and familial (Lynch syndrome) cases of DNA mismatch repair status-deficient colorectal cancer.
• Good practice point

Practice point
Extended RAS mutation testing should be carried out on all patients at the time of diagnosis of metastatic colorectal cancer. Note: RAS testing is not currently pathologist-determinable and therefore can only be performed for metastatic colorectal cancer following a request from a specialist (surgeon or oncologist).

• Guidelines:Colorectal cancer/Additional information pathology reporting#Practice_point_3
• Extended RAS mutation testing should be carried out on all patients at the time of diagnosis of metastatic colorectal cancer. Note: RAS testing is not currently pathologist-determinable and therefore can only be performed for metastatic colorectal cancer following a request from a specialist (surgeon or oncologist).
• Good practice point

Practice point
Synoptic reporting is strongly recommended to capture the key variables to enable translation between major internationally recognised staging systems and facilitate multidisciplinary patient management.

• Guidelines:Colorectal cancer/Additional information pathology reporting#Practice_point_4
• Synoptic reporting is strongly recommended to capture the key variables to enable translation between major internationally recognised staging systems and facilitate multidisciplinary patient management.
• Good practice point

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Optimal molecular profiling

Practice point
A suitable tissue block with a high proportion of tumour tissue (preferably over 70%) should be designated for the purpose of further molecular testing if required.

• Clinical question:Molecular profiling of CRC#Practice_point_1
• A suitable tissue block with a high proportion of tumour tissue (preferably over 70%) should be designated for the purpose of further molecular testing if required.
• Good practice point

Evidence-based recommendation	Grade
RAS mutation studies should be performed on patients with advanced (metastatic) colorectal cancer in whom anti-EGFR treatment is being considered. Cetuximab and panitumumab should only be considered for the treatment of patients with RAS wild-type metastatic colorectal cancer.	D

• Clinical question:Molecular profiling of CRC#Recommendation_1
• RAS mutation studies should be performed on patients with advanced (metastatic) colorectal cancer in whom anti-EGFR treatment is being considered. Cetuximab and panitumumab should only be considered for the treatment of patients with RAS wild-type metastatic colorectal cancer.
• Recommendation

Evidence-based recommendation	Grade
There is emerging evidence suggesting that BRAF mutation may be associated with poor response to anti-EGFR treatment, and that BRAF mutation studies should therefore be performed on patients with advanced (metastatic) colorectal cancer.	D

• Clinical question:Molecular profiling of CRC#Recommendation_2
• There is emerging evidence suggesting that BRAF mutation may be associated with poor response to anti-EGFR treatment, and that BRAF mutation studies should therefore be performed on patients with advanced (metastatic) colorectal cancer.
• Recommendation

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Preparation for surgery and peri-operative optimisation

Multidisciplinary meetings

Practice point
Ideally, all patients with newly diagnosed colorectal cancer should be discussed at a multidisciplinary team meeting.

• Guidelines:Colorectal cancer/Multidisciplinary meetings#Practice_point_1
• Ideally, all patients with newly diagnosed colorectal cancer should be discussed at a multidisciplinary team meeting.
• Good practice point

Practice point
Discussion at a multidisciplinary team meeting is mandatory for high-risk and complex cases such as patients with preoperative rectal cancers, metastatic disease or recurrent disease.

• Guidelines:Colorectal cancer/Multidisciplinary meetings#Practice_point_2
• Discussion at a multidisciplinary team meeting is mandatory for high-risk and complex cases such as patients with preoperative rectal cancers, metastatic disease or recurrent disease.
• Good practice point

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Perioperative anaemia management

Practice point
Patients undergoing elective surgery for colorectal cancer should be assessed for anaemia and iron deficiency and any deficiencies should be addressed preoperatively.

• Guidelines:Colorectal cancer/Perioperative anaemia management#Practice_point_1
• Patients undergoing elective surgery for colorectal cancer should be assessed for anaemia and iron deficiency and any deficiencies should be addressed preoperatively.
• Good practice point

Practice point
Intravenous iron should be considered in preference to oral iron preoperatively given its quicker therapeutic effect.

• Guidelines:Colorectal cancer/Perioperative anaemia management#Practice_point_2
• Intravenous iron should be considered in preference to oral iron preoperatively given its quicker therapeutic effect.
• Good practice point

Practice point
Consideration should also be given to treating postoperative functional iron deficiency anaemia with intravenous iron.

• Guidelines:Colorectal cancer/Perioperative anaemia management#Practice_point_3
• Consideration should also be given to treating postoperative functional iron deficiency anaemia with intravenous iron.
• Good practice point

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Thromboembolic prophylaxis

Practice point
All patients undergoing surgery for colorectal cancer should have standard thromboprophylaxis in hospital with compression stockings, unfractionated or low molecular-weight heparin and sequential compression devices. Extended prophylaxis for 28 days can be considered in high risk patients following colorectal cancer surgery.

• Guidelines:Colorectal cancer/Thromboembolic prophylaxis#Practice_point_1
• All patients undergoing surgery for colorectal cancer should have standard thromboprophylaxis in hospital with compression stockings, unfractionated or low molecular-weight heparin and sequential compression devices. Extended prophylaxis for 28 days can be considered in high risk patients following colorectal cancer surgery.
• Good practice point

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Nutritional interventions

Practice point
Patients undergoing elective surgery for colorectal cancer should be screened for malnutrition.

• Guidelines:Colorectal cancer/Nutritional interventions#Practice_point_1
• Patients undergoing elective surgery for colorectal cancer should be screened for malnutrition.
• Good practice point

Practice point
If patients are found to be malnourished, nutritional interventions should be put in place.

• Guidelines:Colorectal cancer/Nutritional interventions#Practice_point_2
• If patients are found to be malnourished, nutritional interventions should be put in place.
• Good practice point

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Stomal therapy

Practice point
Patients undergoing colorectal cancer surgery who may, or will, require a stoma should be seen prior to surgery by a stomal therapist.

• Guidelines:Colorectal cancer/Stomal therapy#Practice_point_1
• Patients undergoing colorectal cancer surgery who may, or will, require a stoma should be seen prior to surgery by a stomal therapist.
• Good practice point

Practice point
Patients with stomas should be given postoperative education.

• Guidelines:Colorectal cancer/Stomal therapy#Practice_point_2
• Patients with stomas should be given postoperative education.
• Good practice point

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Body temperature

Practice point
Perioperative normothermia should ideally be maintained at or above 36.0˚C.

• Guidelines:Colorectal cancer/Body temperature#Practice_point_1
• Perioperative normothermia should ideally be maintained at or above 36.0˚C.
• Good practice point

Practice point
The use of warmed IV fluids and forced-air warming can be used to minimise perioperative hypothermia.

• Guidelines:Colorectal cancer/Body temperature#Practice_point_2
• The use of warmed IV fluids and forced-air warming can be used to minimise perioperative hypothermia.
• Good practice point

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Enhanced recovery after surgery

Practice point
Patients having elective surgery for colorectal cancer should be managed within an appropriately resourced enhanced recovery after surgery (ERAS) program.

• Guidelines:Colorectal cancer/Enhanced recovery after surgery#Practice_point_1
• Patients having elective surgery for colorectal cancer should be managed within an appropriately resourced enhanced recovery after surgery (ERAS) program.
• Good practice point

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Mechanical bowel preparation with or without antibiotic prophylaxis

Evidence-based recommendation	Grade
Mechanical bowel preparation should not be used routinely in colonic surgery. It can be used selectively according to individual patient and tumour characteristics, at the surgeon’s discretion.	D

• Clinical question:Peri-operative management#Recommendation_1
• Mechanical bowel preparation should not be used routinely in colonic surgery. It can be used selectively according to individual patient and tumour characteristics, at the surgeon’s discretion.
• Recommendation

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Elective and emergency surgery for colon and rectal cancer

Optimal approach to elective resection for colon cancers (COL1-2a)

Evidence-based recommendation	Grade
Either an open approach or a laparoscopic approach can be used for the resection of colon cancer.	D

• Clinical question:Surgical resection colon cancer#Recommendation_1
• Either an open approach or a laparoscopic approach can be used for the resection of colon cancer.
• Recommendation

Evidence-based recommendation	Grade
Laparoscopic colectomy has post-operative advantages over open colectomy and should be performed when the surgical expertise and hospital infrastructure are available.	D

• Clinical question:Surgical resection colon cancer#Recommendation_2
• Laparoscopic colectomy has post-operative advantages over open colectomy and should be performed when the surgical expertise and hospital infrastructure are available.
• Recommendation

Practice point
Laparoscopic colectomy requires significant additional skills. Surgeons should ensure that they have mastered the necessary techniques before performing laparoscopic colectomy as an independent operator.

• Clinical question:Surgical resection colon cancer#Practice_point_1
• Laparoscopic colectomy requires significant additional skills. Surgeons should ensure that they have mastered the necessary techniques before performing laparoscopic colectomy as an independent operator.
• Good practice point

Practice point
Laparoscopic colorectal surgery is complex minimally invasive surgery that requires high-resolution video imaging and up-to-date equipment, including instrumentation and energy sources. It should only be undertaken in facilities that provide this infrastructure.

• Clinical question:Surgical resection colon cancer#Practice_point_2
• Laparoscopic colorectal surgery is complex minimally invasive surgery that requires high-resolution video imaging and up-to-date equipment, including instrumentation and energy sources. It should only be undertaken in facilities that provide this infrastructure.
• Good practice point

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Optimal approach to elective resection for rectal cancers (COL1-2b)

Evidence-based recommendation	Grade
Open surgery is the standard approach for resection of rectal cancer. Laparoscopic resection can be considered in selected cases if the surgical expertise (including advanced laparoscopic skills) and hospital infrastructure are available noting that it is a technique that has yet to be proven safe and efficacious in all patients for rectal cancer.	C

• Clinical question:Surgical resection rectal cancer#Recommendation_1
• Open surgery is the standard approach for resection of rectal cancer. Laparoscopic resection can be considered in selected cases if the surgical expertise (including advanced laparoscopic skills) and hospital infrastructure are available noting that it is a technique that has yet to be proven safe and efficacious in all patients for rectal cancer.
• Recommendation

Practice point

Regardless of the approach utilised, rectal cancer resection must be undertaken by surgeons who have been appropriately trained in surgical resection of rectal cancer, utilising the principles of total mesorectal resection as proposed by Heald. This should include sharp dissection undertaken along the mesorectal plane. Surgical resection undertaken by inadequately trained surgeons is likely to result in inferior oncological outcomes.

• Clinical question:Surgical resection rectal cancer#Practice_point_1
• Regardless of the approach utilised, rectal cancer resection must be undertaken by surgeons who have been appropriately trained in surgical resection of rectal cancer, utilising the principles of total mesorectal resection as proposed by Heald. This should include sharp dissection undertaken along the mesorectal plane. Surgical resection undertaken by inadequately trained surgeons is likely to result in inferior oncological outcomes.
• Good practice point

Practice point
Case selection is important, as it is suboptimal to generalise the surgical approach for rectal cancer to all patients. Factors such as patient body mass index, tumour stage, and surgeon experience are important considerations when determining whether a laparoscopic or open approach is optimal for the patient.

• Clinical question:Surgical resection rectal cancer#Practice_point_2
• Case selection is important, as it is suboptimal to generalise the surgical approach for rectal cancer to all patients. Factors such as patient body mass index, tumour stage, and surgeon experience are important considerations when determining whether a laparoscopic or open approach is optimal for the patient.
• Good practice point

Practice point

The laparoscopic approach may have a higher potential for an inferior quality TME specimen, as demonstrated by two recent multicentre RCTs, though long-term outcome data are not yet available on these studies (Fleshman et al 2015, Stevenson et al 2015). Two other large multicentre RCTs have reported long-term outcomes with no difference in local recurrence or survival (Jeong et al 2014, Bonjer et al 2015). The surgeon should discuss with the patient the potential impact on oncological outcome of the laparoscopic approach along with the potential improvements on short term recovery.

• Clinical question:Surgical resection rectal cancer#Practice_point_3
• The laparoscopic approach may have a higher potential for an inferior quality TME specimen, as demonstrated by two recent multicentre RCTs, though long-term outcome data are not yet available on these studies (Fleshman et al 2015, Stevenson et al 2015). Two other large multicentre RCTs have reported long-term outcomes with no difference in local recurrence or survival (Jeong et al 2014, Bonjer et al 2015). The surgeon should discuss with the patient the potential impact on oncological outcome of the laparoscopic approach along with the potential improvements on short term recovery.
• Good practice point

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Local versus radical resection for T1-T2 rectal tumours (REC3)

Evidence-based recommendation	Grade
For patients with stage 1 rectal cancer (T1/2, N0, M0), cases should be discussed by a multidisciplinary team to determine optimal management with respect to risk of local recurrence, avoidance of a permanent stoma, and fitness for surgery.	C

• Clinical question:Treatment early rectal cancer#Recommendation_1
• For patients with stage 1 rectal cancer (T1/2, N0, M0), cases should be discussed by a multidisciplinary team to determine optimal management with respect to risk of local recurrence, avoidance of a permanent stoma, and fitness for surgery.
• Recommendation

Evidence-based recommendation	Grade
For patients with T1 tumours local excision can be considered, provided that the tumour can be removed with clear margins and that the treating clinician counsels the patient that: the risk of local recurrence increases as the T1 tumour stage progresses (from T1sm1 to T1sm2, or from T1sm2 to T1sm3) radical resection may be required after histopathological review of the local excision specimen.	D

• Clinical question:Treatment early rectal cancer#Recommendation_2
• For patients with T1 tumours local excision can be considered, provided that the tumour can be removed with clear margins and that the treating clinician counsels the patient that:
• the risk of local recurrence increases as the T1 tumour stage progresses (from T1sm1 to T1sm2, or from T1sm2 to T1sm3)
• radical resection may be required after histopathological review of the local excision specimen.
• Recommendation

Evidence-based recommendation	Grade
For patients with T2 tumours, consider radical resection as the first option if they are fit for surgery.	C

• Clinical question:Treatment early rectal cancer#Recommendation_3
• For patients with T2 tumours, consider radical resection as the first option if they are fit for surgery.
• Recommendation

Practice point

When determining the optimal management strategy for each patient, the multidisciplinary team, treating clinician and patient should discuss the balance of risks (e.g. local recurrence) and benefits (e.g. avoidance of a permanent stoma), with consideration of the individual’s fitness for surgery. The treating clinician should explain to the patient that local excision carries a lower risk of perioperative mortality and a lower permanent stoma rate, but is associated with a higher local recurrence rate, which increases as the depth of tumour invasion increases from T1sm1 to T1sm2 to T1sm3 to T2.

• Clinical question:Treatment early rectal cancer#Practice_point_1
• When determining the optimal management strategy for each patient, the multidisciplinary team, treating clinician and patient should discuss the balance of risks (e.g. local recurrence) and benefits (e.g. avoidance of a permanent stoma), with consideration of the individual’s fitness for surgery. The treating clinician should explain to the patient that local excision carries a lower risk of perioperative mortality and a lower permanent stoma rate, but is associated with a higher local recurrence rate, which increases as the depth of tumour invasion increases from T1sm1 to T1sm2 to T1sm3 to T2.
• Good practice point

Practice point
Radical resection is recommended for patients with T1sm3 tumours, and for those with T2 tumours who are considered fit for radical surgery.

• Clinical question:Treatment early rectal cancer#Practice_point_2
• Radical resection is recommended for patients with T1sm3 tumours, and for those with T2 tumours who are considered fit for radical surgery.
• Good practice point

Practice point
The use of transanal endoscopic microsurgery or transanal minimally invasive surgery has not shown any significant advantages over transanal local excision, however it is essential to obtain clear resection margins and the choice of approach to local resection should be determined by the individual surgeon with this factor in mind.

• Clinical question:Treatment early rectal cancer#Practice_point_3
• The use of transanal endoscopic microsurgery or transanal minimally invasive surgery has not shown any significant advantages over transanal local excision, however it is essential to obtain clear resection margins and the choice of approach to local resection should be determined by the individual surgeon with this factor in mind.
• Good practice point

Practice point
Application of radiotherapy before or after local excision of rectal cancer may reduce the risk of local recurrence. However, it may have an adverse effect on bowel function.

• Clinical question:Treatment early rectal cancer#Practice_point_4
• Application of radiotherapy before or after local excision of rectal cancer may reduce the risk of local recurrence. However, it may have an adverse effect on bowel function.
• Good practice point

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Emergency management of malignant large bowel obstruction (COLMNG5)

Evidence-based recommendation	Grade
In patients with acute obstruction due to left-sided colorectal cancer who are potentially curative, the use of stenting as a bridge to surgery is not recommended as standard treatment, due to the potential risk of tumour perforation and conversion of a curative case to a palliative case.	D

• Clinical question:Colonic stents in acute large bowel obstruction#Recommendation_1
• In patients with acute obstruction due to left-sided colorectal cancer who are potentially curative, the use of stenting as a bridge to surgery is not recommended as standard treatment, due to the potential risk of tumour perforation and conversion of a curative case to a palliative case.
• Recommendation

Consensus-based recommendation
The insertion of an intraluminal colonic stent can be considered in large bowel obstruction secondary to colorectal cancer as palliation to relieve large bowel obstruction in patients with incurable metastatic colorectal cancer.

• Clinical question:Colonic stents in acute large bowel obstruction#Practice_point_1
• The insertion of an intraluminal colonic stent can be considered in large bowel obstruction secondary to colorectal cancer as palliation to relieve large bowel obstruction in patients with incurable metastatic colorectal cancer.
• Consensus based recommendation

Consensus-based recommendation
For patients with potentially curable left-sided obstructing colonic cancer who are considered to be at increased risk of post-operative mortality, stent placement may be considered as an alternative to emergency surgery.

• Clinical question:Colonic stents in acute large bowel obstruction#Practice_point_2
• For patients with potentially curable left-sided obstructing colonic cancer who are considered to be at increased risk of post-operative mortality, stent placement may be considered as an alternative to emergency surgery.
• Consensus based recommendation

Consensus-based recommendation
If stenting is considered, it should be discussed by the multidisciplinary team and implications for anti-VEGF systemic therapy should be assessed.

• Clinical question:Colonic stents in acute large bowel obstruction#Practice_point_3
• If stenting is considered, it should be discussed by the multidisciplinary team and implications for anti-VEGF systemic therapy should be assessed.
• Consensus based recommendation

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Peritonectomy with hyperthermic intraperitoneal chemotherapy (COLMNG3)

Evidence-based recommendation	Grade
For patients with colorectal peritoneal metastases (either synchronous or metachronous to the primary), consider cytoreduction with perioperative intraperitoneal chemotherapy. Where this procedure is suitable, offer referral to a centre with the necessary expertise and infrastructure to perform this procedure.	D

• Clinical question:Peritonectomy with HIPEC#Recommendation_1
• For patients with colorectal peritoneal metastases (either synchronous or metachronous to the primary), consider cytoreduction with perioperative intraperitoneal chemotherapy. Where this procedure is suitable, offer referral to a centre with the necessary expertise and infrastructure to perform this procedure.
• Recommendation

Evidence-based recommendation	Grade
Cytoreduction surgery and perioperative intraperitoneal chemotherapy should only be offered after due consideration of, and discussion with the patient about, the potential treatment-related mortality and morbidity.	D

• Clinical question:Peritonectomy with HIPEC#Recommendation_2
• Cytoreduction surgery and perioperative intraperitoneal chemotherapy should only be offered after due consideration of, and discussion with the patient about, the potential treatment-related mortality and morbidity.
• Recommendation

Practice point
Patients with peritoneal carcinomatosis should be referred to a centre with expertise in the management of peritoneal surface malignancies and should be offered enrolment in a prospective trial, so as to allow further evaluation of cytoreduction and intraperitoneal chemotherapy.

• Clinical question:Peritonectomy with HIPEC#Practice_point_1
• Patients with peritoneal carcinomatosis should be referred to a centre with expertise in the management of peritoneal surface malignancies and should be offered enrolment in a prospective trial, so as to allow further evaluation of cytoreduction and intraperitoneal chemotherapy.
• Good practice point

Practice point
Prior to referral, treating clinicians should have an in-depth discussion with every patient about the potential survival advantage and potential treatment-related mortality or morbidity.

• Clinical question:Peritonectomy with HIPEC#Practice_point_2
• Prior to referral, treating clinicians should have an in-depth discussion with every patient about the potential survival advantage and potential treatment-related mortality or morbidity.
• Good practice point

Practice point
All patients’ cases should be discussed at a multidisciplinary team meeting with clinicians who have expertise in the management of peritoneal metastases, to review the relevant clinical information, previous histology (if applicable) and relevant imaging prior to offering patients cytoreductive surgery and intraperitoneal chemotherapy.

• Clinical question:Peritonectomy with HIPEC#Practice_point_3
• All patients’ cases should be discussed at a multidisciplinary team meeting with clinicians who have expertise in the management of peritoneal metastases, to review the relevant clinical information, previous histology (if applicable) and relevant imaging prior to offering patients cytoreductive surgery and intraperitoneal chemotherapy.
• Good practice point

Practice point
All patients offered this procedure in established cytoreduction centres should be asked to give their consent for their patient records to be available for ongoing auditing of clinical outcomes. Patients should also be invited and encouraged to participate in research to enable collection of prospective longitudinal data for clinical and quality-of-life outcomes.

• Clinical question:Peritonectomy with HIPEC#Practice_point_4
• All patients offered this procedure in established cytoreduction centres should be asked to give their consent for their patient records to be available for ongoing auditing of clinical outcomes. Patients should also be invited and encouraged to participate in research to enable collection of prospective longitudinal data for clinical and quality-of-life outcomes.
• Good practice point

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Adjuvant therapy for colon cancer

Adjuvant therapy for stage III colon cancer

Practice point
Oxaliplatin in combination with a fluoropyrimidine is standard therapy for young patients (< 70 years) with stage III colon cancer.

• Guidelines:Colorectal cancer/Adjuvant therapy for stage III colon cancer#Practice_point_1
• Oxaliplatin in combination with a fluoropyrimidine is standard therapy for young patients (< 70 years) with stage III colon cancer.
• Good practice point

Practice point
Capecitabine plus oxaliplatin (XELOX) can be considered as an alternative to FOLFOX for adjuvant treatment for patients with stage III colon cancer.

• Guidelines:Colorectal cancer/Adjuvant therapy for stage III colon cancer#Practice_point_2
• Capecitabine plus oxaliplatin (XELOX) can be considered as an alternative to FOLFOX for adjuvant treatment for patients with stage III colon cancer.
• Good practice point

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Adjuvant therapy for elderly patients with stage III colon cancer

Consensus-based recommendation
Elderly patients (≥ 70 years) with stage III colon cancer who are fit for adjuvant chemotherapy should receive 6 months of a single-agent fluoropyrimidine (either 5FU or capecitabine).

• Clinical question:Adjuvant therapy in elderly CRC patients#Practice_point_1
• Elderly patients (≥ 70 years) with stage III colon cancer who are fit for adjuvant chemotherapy should receive 6 months of a single-agent fluoropyrimidine (either 5FU or capecitabine).
• Consensus based recommendation

Practice point
The addition of oxaliplatin to adjuvant fluoropyrimidine-based therapy in elderly patients (≥ 70 years) with stage III colon cancer did not improve survival outcomes.

• Clinical question:Adjuvant therapy in elderly CRC patients#Practice_point_2
• The addition of oxaliplatin to adjuvant fluoropyrimidine-based therapy in elderly patients (≥ 70 years) with stage III colon cancer did not improve survival outcomes.
• Good practice point

Practice point
The combination of oxaliplatin and fluoropyrimidine-based therapy in the metastatic setting provides a similar benefit in elderly patients and younger patients. The discordance between the adjuvant and metastatic setting remain unexplained.

• Clinical question:Adjuvant therapy in elderly CRC patients#Practice_point_3
• The combination of oxaliplatin and fluoropyrimidine-based therapy in the metastatic setting provides a similar benefit in elderly patients and younger patients. The discordance between the adjuvant and metastatic setting remain unexplained.
• Good practice point

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Adjuvant therapy for stage II colon cancer

Practice point
The optimal approach to adjuvant therapy in stage II colon cancer remains uncertain. Adjuvant therapy can be considered in high-risk patients on a case-by-case basis.

• Guidelines:Colorectal cancer/Adjuvant therapy for stage II colon cancer#Practice_point_1
• The optimal approach to adjuvant therapy in stage II colon cancer remains uncertain. Adjuvant therapy can be considered in high-risk patients on a case-by-case basis.
• Good practice point

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Irinotecan and targeted (biological) agents in adjuvant therapy for stage II and stage III colon cancer

Practice point
Neither Irinotecan nor a biological agent (either bevacizumab or cetuximab) should be used as adjuvant therapy for patients with stage II or III colon cancer.

• Guidelines:Colorectal cancer/Irinotecan and targeted (biological) agents in adjuvant therapy#Practice_point_1
• Neither Irinotecan nor a biological agent (either bevacizumab or cetuximab) should be used as adjuvant therapy for patients with stage II or III colon cancer.
• Good practice point

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Neoadjuvant and adjuvant therapy for rectal cancer

Neoadjuvant therapy for rectal cancer

Practice point
Accurate determination of suitability for neoadjuvant therapy is based on careful preoperative location and staging assessments, and requires optimal quality of care from each aspect of the multidisciplinary team’s assessment.

• Guidelines:Colorectal cancer/Neoadjuvant therapy for rectal cancer#Practice_point_1
• Accurate determination of suitability for neoadjuvant therapy is based on careful preoperative location and staging assessments, and requires optimal quality of care from each aspect of the multidisciplinary team’s assessment.
• Good practice point

Practice point
‘Early’ cT3N0 rectal cancer (<1mm extension) is considered potentially suitable for surgery without neoadjuvant treatment in some international guidelines; but requires a high level of confidence in staging investigations and interpretation.

• Guidelines:Colorectal cancer/Neoadjuvant therapy for rectal cancer#Practice_point_2
• ‘Early’ cT3N0 rectal cancer (<1mm extension) is considered potentially suitable for surgery without neoadjuvant treatment in some international guidelines; but requires a high level of confidence in staging investigations and interpretation.
• Good practice point

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Short-course radiation treatment

Practice point
Preoperative (neoadjuvant) radiation treatment (either short-course radiation treatment alone or long-course chemoradiation) is recommended for most patients with stage II and III rectal cancers, to reduce risk of local recurrence.

• Guidelines:Colorectal cancer/Neoadjuvant short course radiation treatment#Practice_point_1
• Preoperative (neoadjuvant) radiation treatment (either short-course radiation treatment alone or long-course chemoradiation) is recommended for most patients with stage II and III rectal cancers, to reduce risk of local recurrence.
• Good practice point

Practice point
Short-course radiation treatment should be considered if there are clear concerns regarding a patient’s physical or psychosocial ability to tolerate long-course chemoradiation.

• Guidelines:Colorectal cancer/Neoadjuvant short course radiation treatment#Practice_point_2
• Short-course radiation treatment should be considered if there are clear concerns regarding a patient’s physical or psychosocial ability to tolerate long-course chemoradiation.
• Good practice point

Practice point
MRI imaging, patient and clinical factors including comorbidity status should be carefully reviewed by the multidisciplinary team. If clinical T4 primary or nodal disease is seen, or tumour extends close to the mesorectal fascia, then long-course chemoradiation is preferable where possible.

• Guidelines:Colorectal cancer/Neoadjuvant short course radiation treatment#Practice_point_3
• MRI imaging, patient and clinical factors including comorbidity status should be carefully reviewed by the multidisciplinary team. If clinical T4 primary or nodal disease is seen, or tumour extends close to the mesorectal fascia, then long-course chemoradiation is preferable where possible.
• Good practice point

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Neoadjuvant long-course chemoradiation

Evidence-based recommendation	Grade
Consider neoadjuvant chemoradiation for patients with stage II-III rectal cancer where appropriate.	C

• Clinical question:Neoadjuvant chemoradiation vs surgery alone#Recommendation_1
• Consider neoadjuvant chemoradiation for patients with stage II-III rectal cancer where appropriate.
• Recommendation

Practice point
The current standard dose of neoadjuvant chemoradiation is 50–50.4 Gy (boost volume after 45 Gy) with either continuous infusional 5FU or capecitabine.

• Clinical question:Neoadjuvant chemoradiation vs surgery alone#Practice_point_1
• The current standard dose of neoadjuvant chemoradiation is 50–50.4 Gy (boost volume after 45 Gy) with either continuous infusional 5FU or capecitabine.
• Good practice point

Practice point
‘Early’ cT3N0 rectal cancer (<1mm extension) is considered potentially suitable for surgery without neoadjuvant treatment in some international guidelines; but requires a high level of confidence in staging investigations and interpretation.

• Clinical question:Neoadjuvant chemoradiation vs surgery alone#Practice_point_2
• ‘Early’ cT3N0 rectal cancer (<1mm extension) is considered potentially suitable for surgery without neoadjuvant treatment in some international guidelines; but requires a high level of confidence in staging investigations and interpretation.
• Good practice point

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'Watch and wait' approach after clinical complete response to neoadjuvant chemoradiation (NEO1a)

Evidence-based recommendation

Grade

For patients with rectal cancer who have had a clinical complete response to neoadjuvant chemoradiation, and planned resection according to the standard recommendation is either not possible or the patient declines it, a ‘watch and wait’ approach can be considered, provided that: the risks and benefits have been discussed with the multidisciplinary team and the patient the patient is monitored closely for local recurrence the patient is offered an appropriate surgical resection procedure if local recurrence is detected.

D

• Clinical question:Neoadjuvant chemoradiation vs definitive chemoradiation#Recommendation_1
• For patients with rectal cancer who have had a clinical complete response to neoadjuvant chemoradiation, and planned resection according to the standard recommendation is either not possible or the patient declines it, a ‘watch and wait’ approach can be considered, provided that:
• the risks and benefits have been discussed with the multidisciplinary team and the patient
• the patient is monitored closely for local recurrence
• the patient is offered an appropriate surgical resection procedure if local recurrence is detected.
• Recommendation

Practice point
A ‘watch and wait’ approach for patients with clinical complete response following chemoradiation is not considered standard practice. Clinicians and patients who select this option must be aware of increased risk of recurrence necessitating surgical intervention, and the importance of close follow-up.

• Clinical question:Neoadjuvant chemoradiation vs definitive chemoradiation#Practice_point_1
• A ‘watch and wait’ approach for patients with clinical complete response following chemoradiation is not considered standard practice. Clinicians and patients who select this option must be aware of increased risk of recurrence necessitating surgical intervention, and the importance of close follow-up.
• Good practice point

Practice point
Follow-up and surveillance guidelines for a ‘watch and wait’ approach, in particular the frequency of follow-up tests, are not established. Testing may include serial CEA measurements, clinical examination, radiological surveillance, and sigmoidoscopy/colonoscopy.

• Clinical question:Neoadjuvant chemoradiation vs definitive chemoradiation#Practice_point_2
• Follow-up and surveillance guidelines for a ‘watch and wait’ approach, in particular the frequency of follow-up tests, are not established. Testing may include serial CEA measurements, clinical examination, radiological surveillance, and sigmoidoscopy/colonoscopy.
• Good practice point

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Neoadjuvant chemotherapy regimen

Practice point
Infusional fluoropyrimidine is preferable to bolus fluoropyrimidine for use in combination with radiation treatment for rectal cancer.

• Guidelines:Colorectal cancer/Neoadjuvant chemotherapy regimen#Practice_point_1
• Infusional fluoropyrimidine is preferable to bolus fluoropyrimidine for use in combination with radiation treatment for rectal cancer.
• Good practice point

Practice point
Oral capecitabine or intravenous infusional 5FU are both acceptable agents to combine with radiation treatment for rectal cancer.

• Guidelines:Colorectal cancer/Neoadjuvant chemotherapy regimen#Practice_point_2
• Oral capecitabine or intravenous infusional 5FU are both acceptable agents to combine with radiation treatment for rectal cancer.
• Good practice point

Practice point
If capecitabine is considered, patients should be carefully selected to minimise risk of non-compliance or overdosing.

• Guidelines:Colorectal cancer/Neoadjuvant chemotherapy regimen#Practice_point_3
• If capecitabine is considered, patients should be carefully selected to minimise risk of non-compliance or overdosing.
• Good practice point

Practice point
Neoadjuvant oxaliplatin with radiation treatment for rectal cancer is not currently regarded as standard therapy. Data for local control or survival benefit are mixed and oxaliplatin is associated with higher toxicity than fluoropyrimidine alone.

• Guidelines:Colorectal cancer/Neoadjuvant chemotherapy regimen#Practice_point_4
• Neoadjuvant oxaliplatin with radiation treatment for rectal cancer is not currently regarded as standard therapy. Data for local control or survival benefit are mixed and oxaliplatin is associated with higher toxicity than fluoropyrimidine alone.
• Good practice point

Practice point
The role of neoadjuvant systemic chemotherapy is still under investigation and is not regarded as routine.

• Guidelines:Colorectal cancer/Neoadjuvant chemotherapy regimen#Practice_point_5
• The role of neoadjuvant systemic chemotherapy is still under investigation and is not regarded as routine.
• Good practice point

Practice point
The roles of bevacizumab, panitumumab and cetuximab in the neoadjuvant setting for rectal cancer are uncertain, based on available evidence. These are not currently available for the treatment of non-metastatic rectal cancer, and they are not indicated in this setting.

• Guidelines:Colorectal cancer/Neoadjuvant chemotherapy regimen#Practice_point_6
• The roles of bevacizumab, panitumumab and cetuximab in the neoadjuvant setting for rectal cancer are uncertain, based on available evidence. These are not currently available for the treatment of non-metastatic rectal cancer, and they are not indicated in this setting.
• Good practice point

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Optimal timing surgery after neoadjuvant therapy

Practice point
Available data for the optimal timing between completion of neoadjuvant C-RT and surgery indicate that surgery at least 6 weeks but by 12 weeks appears to be appropriate, until results from further studies become available.

• Guidelines:Colorectal cancer/Optimal timing surgery after neoadjuvant therapy#Practice_point_1
• Available data for the optimal timing between completion of neoadjuvant C-RT and surgery indicate that surgery at least 6 weeks but by 12 weeks appears to be appropriate, until results from further studies become available.
• Good practice point

Practice point
Waiting longer within the 6-12 week time frame to allow optimal pathological downstaging may be selected preferentially, for example for patients with T4 tumours, where maximal downstaging is desirable.

• Guidelines:Colorectal cancer/Optimal timing surgery after neoadjuvant therapy#Practice_point_2
• Waiting longer within the 6-12 week time frame to allow optimal pathological downstaging may be selected preferentially, for example for patients with T4 tumours, where maximal downstaging is desirable.
• Good practice point

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Postoperative chemotherapy

Practice point
Strong evidence for benefit of adjuvant chemotherapy for rectal cancer is lacking, even in patients with node positive disease. In disease regarded as high risk, the uncertain benefits of adjuvant chemotherapy should be acknowledged.

• Guidelines:Colorectal cancer/Postoperative chemotherapy#Practice_point_1
• Strong evidence for benefit of adjuvant chemotherapy for rectal cancer is lacking, even in patients with node positive disease. In disease regarded as high risk, the uncertain benefits of adjuvant chemotherapy should be acknowledged.
• Good practice point

Practice point
Patients with upper third rectal tumours (10–15cm from the anal verge) with either cN+ or pN+ findings, are possibly those who may derive any/most benefit from adjuvant chemotherapy.

• Guidelines:Colorectal cancer/Postoperative chemotherapy#Practice_point_2
• Patients with upper third rectal tumours (10–15cm from the anal verge) with either cN+ or pN+ findings, are possibly those who may derive any/most benefit from adjuvant chemotherapy.
• Good practice point

Practice point
For patients with pathological stage II/III rectal cancer, adjuvant oxaliplatin-based chemotherapy is associated with increased toxicities. Benefits, if any, may be confined to those with stage III disease; but not all data concur.

• Guidelines:Colorectal cancer/Postoperative chemotherapy#Practice_point_3
• For patients with pathological stage II/III rectal cancer, adjuvant oxaliplatin-based chemotherapy is associated with increased toxicities. Benefits, if any, may be confined to those with stage III disease; but not all data concur.
• Good practice point

Practice point
The uncertain benefits of oxaliplatin as adjuvant therapy in rectal cancer should be acknowledged.

• Guidelines:Colorectal cancer/Postoperative chemotherapy#Practice_point_4
• The uncertain benefits of oxaliplatin as adjuvant therapy in rectal cancer should be acknowledged.
• Good practice point

Practice point
There are no randomised trials for adjuvant chemotherapy for patients with pathological complete response after chemoradiation followed by surgery. Available evidence suggests that these patients have a very good prognosis and any absolute benefits are likely to be small.

• Guidelines:Colorectal cancer/Postoperative chemotherapy#Practice_point_5
• There are no randomised trials for adjuvant chemotherapy for patients with pathological complete response after chemoradiation followed by surgery. Available evidence suggests that these patients have a very good prognosis and any absolute benefits are likely to be small.
• Good practice point

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Postoperative radiation treatment

Practice point
Patients with higher risk disease post-operatively who did not receive neoadjuvant treatment should be considered for adjuvant pelvic radiotherapy concurrent with 5 fluorouracil chemotherapy.

• Guidelines:Colorectal cancer/Postoperative radiation treatment#Practice_point_1
• Patients with higher risk disease post-operatively who did not receive neoadjuvant treatment should be considered for adjuvant pelvic radiotherapy concurrent with 5 fluorouracil chemotherapy.
• Good practice point

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Management of resectable locally recurrent disease and metastatic disease

Investigation of recurrent cancer

Practice point
Initial assessment of patients with suspected local or systematic recurrence should include serum CEA, contrast CT scan of the chest, abdomen and pelvis (unless contraindicated) and PET.

• Guidelines:Colorectal cancer/Investigation of recurrent cancer#Practice_point_1
• Initial assessment of patients with suspected local or systematic recurrence should include serum CEA, contrast CT scan of the chest, abdomen and pelvis (unless contraindicated) and PET.
• Good practice point

Practice point

Depending on the type of recurrence, additional investigations are likely to be necessary. A high-quality pelvic MRI is recommended for patients with locally recurrent rectal cancer. Additional local investigations may also need to be considered depending on patient and disease factors such as CT or MRA if mesenteric or iliac vessel involvement is suspected, or cystoscopy if bladder involvement is suspected.

• Guidelines:Colorectal cancer/Investigation of recurrent cancer#Practice_point_2
• Depending on the type of recurrence, additional investigations are likely to be necessary. A high-quality pelvic MRI is recommended for patients with locally recurrent rectal cancer. Additional local investigations may also need to be considered depending on patient and disease factors such as CT or MRA if mesenteric or iliac vessel involvement is suspected, or cystoscopy if bladder involvement is suspected.
• Good practice point

Practice point
If possible, local recurrence should be histologically confirmed before surgery. If this is not possible because of the extraluminal location of the disease, a transvaginal biopsy may be feasible where the recurrence abuts the vagina. Alternatively, CT-guided percutaneous biopsies can be considered after assessing the need for biopsy at a multidisciplinary team meeting.

• Guidelines:Colorectal cancer/Investigation of recurrent cancer#Practice_point_3
• If possible, local recurrence should be histologically confirmed before surgery. If this is not possible because of the extraluminal location of the disease, a transvaginal biopsy may be feasible where the recurrence abuts the vagina. Alternatively, CT-guided percutaneous biopsies can be considered after assessing the need for biopsy at a multidisciplinary team meeting.
• Good practice point

Practice point
In patients with liver metastases, an MRI of the liver is usually also necessary if surgery is being considered. The use of disodium gadoxetate (Primovist) contrast can increase the sensitivity and specificity of MRI for detecting liver metastases. Colonoscopy may be needed if further resection is planned.

• Guidelines:Colorectal cancer/Investigation of recurrent cancer#Practice_point_4
• In patients with liver metastases, an MRI of the liver is usually also necessary if surgery is being considered. The use of disodium gadoxetate (Primovist) contrast can increase the sensitivity and specificity of MRI for detecting liver metastases. Colonoscopy may be needed if further resection is planned.
• Good practice point

Practice point
In patients with suspected lung metastases, CT chest and PET are usually sufficient to confirm diagnosis. In patients where there is diagnostic uncertainty or concerns for mediastinal nodal involvement, an endobronchial ultrasound or bronchoscopy may be needed.

• Guidelines:Colorectal cancer/Investigation of recurrent cancer#Practice_point_5
• In patients with suspected lung metastases, CT chest and PET are usually sufficient to confirm diagnosis. In patients where there is diagnostic uncertainty or concerns for mediastinal nodal involvement, an endobronchial ultrasound or bronchoscopy may be needed.
• Good practice point

Practice point
All patients with locally recurrent disease or metastatic disease should be discussed in a multidisciplinary team meeting taking into consideration patient’s previous surgical history, current imaging, fitness and desire for further treatment.

• Guidelines:Colorectal cancer/Investigation of recurrent cancer#Practice_point_6
• All patients with locally recurrent disease or metastatic disease should be discussed in a multidisciplinary team meeting taking into consideration patient’s previous surgical history, current imaging, fitness and desire for further treatment.
• Good practice point

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Management of locally recurrent resectable colorectal cancer

Evidence-based recommendation	Grade
For patients with isolated local recurrence of rectal cancer, consider referral to a centre with the necessary expertise to perform curative surgery (also known as pelvic exenteration).	D

• Clinical question:Management recurrent, resectable CRC#Recommendation_1
• For patients with isolated local recurrence of rectal cancer, consider referral to a centre with the necessary expertise to perform curative surgery (also known as pelvic exenteration).
• Recommendation

Evidence-based recommendation	Grade
Re-operative surgery for locally recurrent rectal cancer should only be offered after due consideration of, and discussion with the patient about, the potential survival advantage, quality-of-life outcomes, and potential treatment-related morbidity.	D

• Clinical question:Management recurrent, resectable CRC#Recommendation_2
• Re-operative surgery for locally recurrent rectal cancer should only be offered after due consideration of, and discussion with the patient about, the potential survival advantage, quality-of-life outcomes, and potential treatment-related morbidity.
• Recommendation

Consensus-based recommendation
Patients who have not previously received radiotherapy should be considered for neoadjuvant chemoradiation prior to re-operative surgery.

• Clinical question:Management recurrent, resectable CRC#Practice_point_1
• Patients who have not previously received radiotherapy should be considered for neoadjuvant chemoradiation prior to re-operative surgery.
• Consensus based recommendation

Practice point
Patients with locally recurrent colorectal cancer should be referred to a centre with the expertise in the management of these cancers.

• Clinical question:Management recurrent, resectable CRC#Practice_point_2
• Patients with locally recurrent colorectal cancer should be referred to a centre with the expertise in the management of these cancers.
• Good practice point

Practice point
All patients with locally recurrent colorectal cancer should be discussed at a multi-disciplinary team meeting with clinicians who have the expertise in the management of such malignancies. These meetings should review the patient’s previous histology and relevant imaging prior to making an appropriate clinical recommendation.

• Clinical question:Management recurrent, resectable CRC#Practice_point_3
• All patients with locally recurrent colorectal cancer should be discussed at a multi-disciplinary team meeting with clinicians who have the expertise in the management of such malignancies. These meetings should review the patient’s previous histology and relevant imaging prior to making an appropriate clinical recommendation.
• Good practice point

Practice point
Re-operative surgery for locally recurrent colorectal cancer can be associated with significant morbidity. As such, all re-resections should only be offered when cure is considered possible.

• Clinical question:Management recurrent, resectable CRC#Practice_point_4
• Re-operative surgery for locally recurrent colorectal cancer can be associated with significant morbidity. As such, all re-resections should only be offered when cure is considered possible.
• Good practice point

Practice point
The key factor in achieving long-term survival in patients with locally recurrent colorectal cancer is a complete resection with clear resection margins (R0 margins), which is an important consideration when making clinical decision about disease resectability.

• Clinical question:Management recurrent, resectable CRC#Practice_point_5
• The key factor in achieving long-term survival in patients with locally recurrent colorectal cancer is a complete resection with clear resection margins (R0 margins), which is an important consideration when making clinical decision about disease resectability.
• Good practice point

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Management of resectable metastatic colorectal cancer (MNG14)

Evidence-based recommendation	Grade
In patients with resectable liver metastases, liver resection should be offered, as this improves overall and progression free survival.	D

• Clinical question:Management metastatic resectable CRC#Recommendation_1
• In patients with resectable liver metastases, liver resection should be offered, as this improves overall and progression free survival.
• Recommendation

Evidence-based recommendation	Grade
Patients referred for liver resection should be counselled about the potential complications associated with liver resection in comparison with non-curative treatments.	D

• Clinical question:Management metastatic resectable CRC#Recommendation_2
• Patients referred for liver resection should be counselled about the potential complications associated with liver resection in comparison with non-curative treatments.
• Recommendation

Consensus-based recommendation
Patients at higher risk of recurrence should receive adjuvant therapy following liver resection, so as to reduce the likelihood of further local or systemic recurrences.

• Clinical question:Management metastatic resectable CRC#Practice_point_1
• Patients at higher risk of recurrence should receive adjuvant therapy following liver resection, so as to reduce the likelihood of further local or systemic recurrences.
• Consensus based recommendation

Consensus-based recommendation
For patients with liver metastases that are considered ‘borderline’ resectable, neoadjuvant chemotherapy should be considered and the case should be discussed by a multidisciplinary team that includes an experienced liver surgeon.

• Clinical question:Management metastatic resectable CRC#Practice_point_2
• For patients with liver metastases that are considered ‘borderline’ resectable, neoadjuvant chemotherapy should be considered and the case should be discussed by a multidisciplinary team that includes an experienced liver surgeon.
• Consensus based recommendation

Consensus-based recommendation
In patients with pulmonary metastases, pulmonary resection improves locoregional control and may improve survival.

• Clinical question:Management metastatic resectable CRC#Practice_point_3
• In patients with pulmonary metastases, pulmonary resection improves locoregional control and may improve survival.
• Consensus based recommendation

Consensus-based recommendation
Systemic adjuvant chemotherapy following complete resection of pulmonary metastases may reduce the likelihood of further systemic or local recurrences.

• Clinical question:Management metastatic resectable CRC#Practice_point_4
• Systemic adjuvant chemotherapy following complete resection of pulmonary metastases may reduce the likelihood of further systemic or local recurrences.
• Consensus based recommendation

Consensus-based recommendation

In patients with liver and lung metastases, curative treatment may still be feasible. Combined or staged resection of the metastases may be possible provided both the liver and lung metastases can be completely resected and after taking into account the anatomic as well as functional considerations of the remnant liver and lung. Furthermore, lung resection may be considered in patients who have previously undergone a liver resection and vice versa. The use of neoadjuvant chemotherapy with subsequent restaging may also be considered in patients with synchronous liver and lung metastases prior to offering definitive resection.

• Clinical question:Management metastatic resectable CRC#Practice_point_5
• In patients with liver and lung metastases, curative treatment may still be feasible. Combined or staged resection of the metastases may be possible provided both the liver and lung metastases can be completely resected and after taking into account the anatomic as well as functional considerations of the remnant liver and lung. Furthermore, lung resection may be considered in patients who have previously undergone a liver resection and vice versa. The use of neoadjuvant chemotherapy with subsequent restaging may also be considered in patients with synchronous liver and lung metastases prior to offering definitive resection.
• Consensus based recommendation

Consensus-based recommendation
In patients with other isolated metastases, metasectomy may be appropriate in a well-informed patient after appropriate investigations and discussion in a multi-disciplinary team meeting.

• Clinical question:Management metastatic resectable CRC#Practice_point_6
• In patients with other isolated metastases, metasectomy may be appropriate in a well-informed patient after appropriate investigations and discussion in a multi-disciplinary team meeting.
• Consensus based recommendation

Practice point
Patients with liver metastases should be referred to a centre with expertise in the management of these malignancies, for consideration of liver resection, if appropriate.

• Clinical question:Management metastatic resectable CRC#Practice_point_7
• Patients with liver metastases should be referred to a centre with expertise in the management of these malignancies, for consideration of liver resection, if appropriate.
• Good practice point

Practice point
Following curative treatment of liver metastases, patients need ongoing regular follow-up so as to permit early detection of further recurrences that may be amendable to further therapy.

• Clinical question:Management metastatic resectable CRC#Practice_point_8
• Following curative treatment of liver metastases, patients need ongoing regular follow-up so as to permit early detection of further recurrences that may be amendable to further therapy.
• Good practice point

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Management of non-resectable locally recurrent disease and metastatic disease

Liver-directed therapies for patients with incurable metastatic colorectal cancer

Evidence-based recommendation	Grade
For patients with non-resectable liver metastases of colorectal cancer, liver-directed therapies (selective internal radiation treatment, radiofrequency ablation, hepatic arterial infusion of chemotherapy agents or transarterial chemoembolisation) can be considered in centres with expertise in the specific technique after multidisciplinary team discussion, or in the context of a clinical trial.	D

• Clinical question:Liver directed therapies unresectable metastatic CRC#Recommendation_1
• For patients with non-resectable liver metastases of colorectal cancer, liver-directed therapies (selective internal radiation treatment, radiofrequency ablation, hepatic arterial infusion of chemotherapy agents or transarterial chemoembolisation) can be considered in centres with expertise in the specific technique after multidisciplinary team discussion, or in the context of a clinical trial.
• Recommendation

Consensus-based recommendation

In patients with non-resectable liver metastases only (or oligometastatic disease) liver directed techniques can be considered by the MDT based on local experience, patient preference and tumour characteristics. Treating clinicians should have an in-depth discussion with every patient regarding technical complexity, potential outcomes and complications in addition to other therapies available for that patient.

• Clinical question:Liver directed therapies unresectable metastatic CRC#Practice_point_1
• In patients with non-resectable liver metastases only (or oligometastatic disease) liver directed techniques can be considered by the MDT based on local experience, patient preference and tumour characteristics. Treating clinicians should have an in-depth discussion with every patient regarding technical complexity, potential outcomes and complications in addition to other therapies available for that patient.
• Consensus based recommendation

Practice point
All patients with metastatic colorectal cancer should be discussed at a multidisciplinary team meeting with clinicians who have expertise in management of metastatic colorectal cancer.

• Clinical question:Liver directed therapies unresectable metastatic CRC#Practice_point_2
• All patients with metastatic colorectal cancer should be discussed at a multidisciplinary team meeting with clinicians who have expertise in management of metastatic colorectal cancer.
• Good practice point

Practice point
For patients who could be considered surgical candidates if their metastases were smaller, we suggest initial systemic chemotherapy followed by re-evaluation for surgery.

• Clinical question:Liver directed therapies unresectable metastatic CRC#Practice_point_3
• For patients who could be considered surgical candidates if their metastases were smaller, we suggest initial systemic chemotherapy followed by re-evaluation for surgery.
• Good practice point

Practice point
Wherever possible, patients considering liver-directed therapies should be enrolled into clinical trials examining these treatments in comparison to standard therapies.

• Clinical question:Liver directed therapies unresectable metastatic CRC#Practice_point_4
• Wherever possible, patients considering liver-directed therapies should be enrolled into clinical trials examining these treatments in comparison to standard therapies.
• Good practice point

Practice point
SIRT in combination with systemic chemotherapy can be used to prolong the time to liver progression but not improve colorectal cancer survival with most evidence currently in the chemo-refractory patients. At present there is insufficient data to recommend SIRT in the first line setting for patients with non-resectable mCRC.

• Clinical question:Liver directed therapies unresectable metastatic CRC#Practice_point_5
• SIRT in combination with systemic chemotherapy can be used to prolong the time to liver progression but not improve colorectal cancer survival with most evidence currently in the chemo-refractory patients. At present there is insufficient data to recommend SIRT in the first line setting for patients with non-resectable mCRC.
• Good practice point

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Management of synchronous primary colorectal cancer with unresectable metastatic disease

Practice point
Routine palliative resection of asymptomatic synchronous primary lesion in patients with unresectable metastatic colorectal cancer remains controversial and there are no prospective randomised studies to guide treatment. Recruitment into such trials has been difficult.

• Clinical question:Management synchronous primary in metastatic CRC#Practice_point_1
• Routine palliative resection of asymptomatic synchronous primary lesion in patients with unresectable metastatic colorectal cancer remains controversial and there are no prospective randomised studies to guide treatment. Recruitment into such trials has been difficult.
• Good practice point

Practice point
All patients with an asymptomatic primary and unresectable metastatic colorectal cancer should be discussed in a multi-disciplinary team meeting and the risks and benefits of a palliative resection for an individual patient be carefully discussed bearing in mind the volume of metastatic disease, degree of stenosis/risk of impending obstruction, comorbidities and patient preferences.

• Clinical question:Management synchronous primary in metastatic CRC#Practice_point_2
• All patients with an asymptomatic primary and unresectable metastatic colorectal cancer should be discussed in a multi-disciplinary team meeting and the risks and benefits of a palliative resection for an individual patient be carefully discussed bearing in mind the volume of metastatic disease, degree of stenosis/risk of impending obstruction, comorbidities and patient preferences.
• Good practice point

Practice point
Patients with an asymptomatic primary and good medium to long term disease control after initial systemic therapy could be re-evaluated for potential resection of both the primary tumour and metastases in the absence of widespread disease progression.

• Clinical question:Management synchronous primary in metastatic CRC#Practice_point_3
• Patients with an asymptomatic primary and good medium to long term disease control after initial systemic therapy could be re-evaluated for potential resection of both the primary tumour and metastases in the absence of widespread disease progression.
• Good practice point

Practice point

For patients with a symptomatic primary tumour (obstruction, bleeding or perforation) and synchronous metastatic disease, resection of the primary tumour should be considered before initiation of systemic therapy. For candidates not suitable for primary tumour resection other palliative options to control symptoms including surgical bypass, radiotherapy, stents, laser ablation in addition to systemic treatment should be considered.

• Clinical question:Management synchronous primary in metastatic CRC#Practice_point_4
• For patients with a symptomatic primary tumour (obstruction, bleeding or perforation) and synchronous metastatic disease, resection of the primary tumour should be considered before initiation of systemic therapy. For candidates not suitable for primary tumour resection other palliative options to control symptoms including surgical bypass, radiotherapy, stents, laser ablation in addition to systemic treatment should be considered.
• Good practice point

Practice point
For patients with unresectable metastatic rectal cancer with symptomatic primary tumour, irradiation (+/- chemotherapy) of the primary tumour should be considered after multidisciplinary discussion in order to obtain optimal symptom control and reduce patient morbidity.

• Clinical question:Management synchronous primary in metastatic CRC#Practice_point_5
• For patients with unresectable metastatic rectal cancer with symptomatic primary tumour, irradiation (+/- chemotherapy) of the primary tumour should be considered after multidisciplinary discussion in order to obtain optimal symptom control and reduce patient morbidity.
• Good practice point

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The role of systemic therapies in non-resectable metastatic disease

Molecular pathology and biomarkers – implications for systemic therapy

Practice point
RAS testing should be carried out on all patients at the time of diagnosis of metastatic colorectal cancer.

• Guidelines:Colorectal cancer/Systemic therapy molecular pathology#Practice_point_1
• RAS testing should be carried out on all patients at the time of diagnosis of metastatic colorectal cancer.
• Good practice point

Practice point
RAS mutational status is a negative predictive biomarker for therapeutic choices involving EGFR antibody therapies in metastatic colorectal cancer.

• Guidelines:Colorectal cancer/Systemic therapy molecular pathology#Practice_point_2
• RAS mutational status is a negative predictive biomarker for therapeutic choices involving EGFR antibody therapies in metastatic colorectal cancer.
• Good practice point

Practice point
Cetuximab and panitumumab should only be considered for the treatment of patients with RAS wild-type metastatic colorectal cancer.

• Guidelines:Colorectal cancer/Systemic therapy molecular pathology#Practice_point_3
• Cetuximab and panitumumab should only be considered for the treatment of patients with RAS wild-type metastatic colorectal cancer.
• Good practice point

Practice point
The BRAF mutation status should ideally be performed at the time of diagnosis of metastatic colorectal cancer, as this represents a distinct biologic subtype.

• Guidelines:Colorectal cancer/Systemic therapy molecular pathology#Practice_point_4
• The BRAF mutation status should ideally be performed at the time of diagnosis of metastatic colorectal cancer, as this represents a distinct biologic subtype.
• Good practice point

Practice point
The presence of a BRAF mutation in metastatic colorectal cancer is considered a poor prognostic marker.

• Guidelines:Colorectal cancer/Systemic therapy molecular pathology#Practice_point_5
• The presence of a BRAF mutation in metastatic colorectal cancer is considered a poor prognostic marker.
• Good practice point

Practice point
BRAF mutation status in combination with testing for DNA mismatch repair deficiency can assist in the identification of a germline versus somatic cause of DNA mismatch repair deficiency.

• Guidelines:Colorectal cancer/Systemic therapy molecular pathology#Practice_point_6
• BRAF mutation status in combination with testing for DNA mismatch repair deficiency can assist in the identification of a germline versus somatic cause of DNA mismatch repair deficiency.
• Good practice point

Practice point
The preponderance of the available evidence is that response to EGFR-targeted agents is less likely in patients whose tumours harbour a BRAF mutation.

• Guidelines:Colorectal cancer/Systemic therapy molecular pathology#Practice_point_7
• The preponderance of the available evidence is that response to EGFR-targeted agents is less likely in patients whose tumours harbour a BRAF mutation.
• Good practice point

Practice point
Metastatic colorectal cancer patients with a BRAF mutation should be considered for a clinical trial where available or triplet chemotherapy if suitable.

• Guidelines:Colorectal cancer/Systemic therapy molecular pathology#Practice_point_8
• Metastatic colorectal cancer patients with a BRAF mutation should be considered for a clinical trial where available or triplet chemotherapy if suitable.
• Good practice point

Practice point
MSI testing in the metastatic setting can be useful to help identify patients who require referral for further genetic testing and counselling.

• Guidelines:Colorectal cancer/Systemic therapy molecular pathology#Practice_point_9
• MSI testing in the metastatic setting can be useful to help identify patients who require referral for further genetic testing and counselling.
• Good practice point

Practice point
BRAF V600 mutational analysis should be done in conjunction with MSI testing for prognostic stratification.

• Guidelines:Colorectal cancer/Systemic therapy molecular pathology#Practice_point_10
• BRAF V600 mutational analysis should be done in conjunction with MSI testing for prognostic stratification.
• Good practice point

Practice point
MSI testing may be a predictive marker for the use of immune checkpoint inhibitors in the treatment of patients with metastatic colorectal cancer.

• Guidelines:Colorectal cancer/Systemic therapy molecular pathology#Practice_point_11
• MSI testing may be a predictive marker for the use of immune checkpoint inhibitors in the treatment of patients with metastatic colorectal cancer.
• Good practice point

Practice point
Emerging biomarkers are not recommended for routine patient management outside of the clinical trial setting.

• Guidelines:Colorectal cancer/Systemic therapy molecular pathology#Practice_point_12
• Emerging biomarkers are not recommended for routine patient management outside of the clinical trial setting.
• Good practice point

Practice point
The location of the primary tumour is a strong prognostic factor. Patients with left sided primary tumours have a favourable outcome compared with those with right sided tumours regardless of treatment type received.

• Guidelines:Colorectal cancer/Systemic therapy molecular pathology#Practice_point_13
• The location of the primary tumour is a strong prognostic factor. Patients with left sided primary tumours have a favourable outcome compared with those with right sided tumours regardless of treatment type received.
• Good practice point

Practice point
Left sided colorectal cancer should be considered for initial doublet chemotherapy and anti-EGFR therapy where appropriate. Alternate options remain appropriate based on patient preference and comorbidity.

• Guidelines:Colorectal cancer/Systemic therapy molecular pathology#Practice_point_14
• Left sided colorectal cancer should be considered for initial doublet chemotherapy and anti-EGFR therapy where appropriate. Alternate options remain appropriate based on patient preference and comorbidity.
• Good practice point

Practice point

Right sided colorectal cancer should be considered for initial doublet chemotherapy plus or minus anti-VEGF. There may be a role for initial chemotherapy with anti-EGFR in right sided colon cancer where the aim of treatment is down staging for resection given the improved response with anti-EGFR. However, this should be done with caution given the lack of benefit on overall survival or progression free survival.

• Guidelines:Colorectal cancer/Systemic therapy molecular pathology#Practice_point_15
• Right sided colorectal cancer should be considered for initial doublet chemotherapy plus or minus anti-VEGF. There may be a role for initial chemotherapy with anti-EGFR in right sided colon cancer where the aim of treatment is down staging for resection given the improved response with anti-EGFR. However, this should be done with caution given the lack of benefit on overall survival or progression free survival.
• Good practice point

Practice point
Sequential use of all available therapies should continue to be utilised in patients with colorectal cancer regardless of the side of the primary tumour, provided it is appropriate for the individual patient.

• Guidelines:Colorectal cancer/Systemic therapy molecular pathology#Practice_point_16
• Sequential use of all available therapies should continue to be utilised in patients with colorectal cancer regardless of the side of the primary tumour, provided it is appropriate for the individual patient.
• Good practice point

Practice point
Future trials for colon cancer should stratify patients by 'sidedness,' to better understand this issue.

• Guidelines:Colorectal cancer/Systemic therapy molecular pathology#Practice_point_17
• Future trials for colon cancer should stratify patients by 'sidedness,' to better understand this issue.
• Good practice point

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Systemic chemotherapy treatment options for first-line treatment

Practice point
For patients who are able to tolerate it, combination chemotherapy with a doublet (FOLFOX, XELOX [CAPOX], or FOLFIRI) rather than a single agent sequential therapy for initial treatment of metastatic colorectal cancer, is preferred.

• Guidelines:Colorectal cancer/Systemic chemotherapy first-line treatment#Practice_point_1
• For patients who are able to tolerate it, combination chemotherapy with a doublet (FOLFOX, XELOX [CAPOX], or FOLFIRI) rather than a single agent sequential therapy for initial treatment of metastatic colorectal cancer, is preferred.
• Good practice point

Practice point
Patients with potentially resectable metastatic disease should be discussed at a multidisciplinary meeting, and treatment plans should consider patient comorbidity and suitability for an aggressive treatment strategy

• Guidelines:Colorectal cancer/Systemic chemotherapy first-line treatment#Practice_point_2
• Patients with potentially resectable metastatic disease should be discussed at a multidisciplinary meeting, and treatment plans should consider patient comorbidity and suitability for an aggressive treatment strategy
• Good practice point

Practice point
Monotherapy is not appropriate and combination chemotherapy with a doublet (FOLFOX, XELOX [CAPOX], or FOLRIR) should be used where the aim of therapy is significant cytoreduction. For those with RAS wild-type tumours, an anti-EGFR antibody in conjunction with combination chemotherapy can be considered especially in those with left sided primaries.

• Guidelines:Colorectal cancer/Systemic chemotherapy first-line treatment#Practice_point_3
• Monotherapy is not appropriate and combination chemotherapy with a doublet (FOLFOX, XELOX [CAPOX], or FOLRIR) should be used where the aim of therapy is significant cytoreduction. For those with RAS wild-type tumours, an anti-EGFR antibody in conjunction with combination chemotherapy can be considered especially in those with left sided primaries.
• Good practice point

Practice point
For those with good performance status and without significant comorbidities intensive triplet chemotherapy with FOLFIRINOX can be considered.

• Guidelines:Colorectal cancer/Systemic chemotherapy first-line treatment#Practice_point_4
• For those with good performance status and without significant comorbidities intensive triplet chemotherapy with FOLFIRINOX can be considered.
• Good practice point

Practice point
Patient comorbidities, ECOG performance status, and location and burden of metastatic disease should be considered in treatment decisions.

• Guidelines:Colorectal cancer/Systemic chemotherapy first-line treatment#Practice_point_5
• Patient comorbidities, ECOG performance status, and location and burden of metastatic disease should be considered in treatment decisions.
• Good practice point

Practice point
For patients who are medically unfit with poor performance status, a supportive care approach may be appropriate.

• Guidelines:Colorectal cancer/Systemic chemotherapy first-line treatment#Practice_point_6
• For patients who are medically unfit with poor performance status, a supportive care approach may be appropriate.
• Good practice point

Practice point
In patients with poor performance status or significant comorbidities palliative treatment with single agent fluoropyrimidine (with or without bevacizumab) may be preferred to doublet chemotherapy. Fluoropyrimidine-based therapy alone (or in combination with bevacizumab) can be considered in patients with low-volume unresectable disease.

• Guidelines:Colorectal cancer/Systemic chemotherapy first-line treatment#Practice_point_7
• In patients with poor performance status or significant comorbidities palliative treatment with single agent fluoropyrimidine (with or without bevacizumab) may be preferred to doublet chemotherapy. Fluoropyrimidine-based therapy alone (or in combination with bevacizumab) can be considered in patients with low-volume unresectable disease.
• Good practice point

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Role of biological agents in first-line treatment of metastatic colorectal cancer

Practice point
Biological agents targeting EGFR or VEGF in combination with chemotherapy are recommended in the first-line treatment of most patients unless contraindicated.

• Guidelines:Colorectal cancer/Biological agents first-line treatment of metastatic CRC#Practice_point_1
• Biological agents targeting EGFR or VEGF in combination with chemotherapy are recommended in the first-line treatment of most patients unless contraindicated.
• Good practice point

Practice point
EGFR antibodies should: be used in patients with RAS wild-type tumours be used in combination with FOLFIRI or FOLFOX not be combined with capecitabine-based and bolus 5FU-based regimen.

• Guidelines:Colorectal cancer/Biological agents first-line treatment of metastatic CRC#Practice_point_2
• EGFR antibodies should:
• be used in patients with RAS wild-type tumours
• be used in combination with FOLFIRI or FOLFOX
• not be combined with capecitabine-based and bolus 5FU-based regimen.
• Good practice point

Practice point
Patients with left sided colorectal cancer should be considered for initial doublet chemotherapy and anti-EGFR therapy where appropriate. Alternate options remain appropriate based on patient preference and comorbidity.See left vs. right section

• Guidelines:Colorectal cancer/Biological agents first-line treatment of metastatic CRC#Practice_point_3
• Patients with left sided colorectal cancer should be considered for initial doublet chemotherapy and anti-EGFR therapy where appropriate. Alternate options remain appropriate based on patient preference and comorbidity.See left vs. right section
• Good practice point

Practice point
EGFR antibodies may be less efficacious in patients with BRAF mutations.

• Guidelines:Colorectal cancer/Biological agents first-line treatment of metastatic CRC#Practice_point_4
• EGFR antibodies may be less efficacious in patients with BRAF mutations.
• Good practice point

Practice point

VEGF antibody (bevacizumab): should be used in combination with cytotoxic doublets including FOLFOX, XELOX and FOLFIRI can be used in combination with the triplet cytotoxic regimen FOLFOXIRI in select fit patients where tumour shrinkage is the goal, and potentially in fit patients with a BRAF mutation can be used in combination with fluoropyrimidine monotherapy in less fit patients unlikely to be suitable for a doublet cytotoxic regimen.

• Guidelines:Colorectal cancer/Biological agents first-line treatment of metastatic CRC#Practice_point_5
• VEGF antibody (bevacizumab):
• should be used in combination with cytotoxic doublets including FOLFOX, XELOX and FOLFIRI
• can be used in combination with the triplet cytotoxic regimen FOLFOXIRI in select fit patients where tumour shrinkage is the goal, and potentially in fit patients with a BRAF mutation
• can be used in combination with fluoropyrimidine monotherapy in less fit patients unlikely to be suitable for a doublet cytotoxic regimen.
• Good practice point

Practice point
Patients with right sided colorectal cancer should be considered for initial doublet chemotherapy plus or minus anti-VEGF. See left vs. right section

• Guidelines:Colorectal cancer/Biological agents first-line treatment of metastatic CRC#Practice_point_6
• Patients with right sided colorectal cancer should be considered for initial doublet chemotherapy plus or minus anti-VEGF. See left vs. right section
• Good practice point

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Subsequent treatment and the continuum-of-care model

Practice point
Individualisation and discussion with the patient is essential when planning treatment breaks and or de-escalation/maintenance schedules.

• Guidelines:Colorectal cancer/Treatment and continuum-of-care model#Practice_point_1
• Individualisation and discussion with the patient is essential when planning treatment breaks and or de-escalation/maintenance schedules.
• Good practice point

Practice point
When the combination of leucovorin calcium (folinic acid), 5-fluorouracil (5FU) and oxaliplatin (FOLFOX), with or without bevacizumab, is used for first-line therapy, the available data suggest that it is reasonable to discontinue oxaliplatin temporarily while maintaining a fluoropyrimidine with or without bevacizumab.

• Guidelines:Colorectal cancer/Treatment and continuum-of-care model#Practice_point_2
• When the combination of leucovorin calcium (folinic acid), 5-fluorouracil (5FU) and oxaliplatin (FOLFOX), with or without bevacizumab, is used for first-line therapy, the available data suggest that it is reasonable to discontinue oxaliplatin temporarily while maintaining a fluoropyrimidine with or without bevacizumab.
• Good practice point

Practice point
When the combination of folinic acid, 5FU and irinotecan hydrochloride (FOLFIRI), with or without bevacizumab, is used for first- line therapy, patients can continue on induction therapy for as long as tumour shrinkage continues and the treatment is tolerable.

• Guidelines:Colorectal cancer/Treatment and continuum-of-care model#Practice_point_3
• When the combination of folinic acid, 5FU and irinotecan hydrochloride (FOLFIRI), with or without bevacizumab, is used for first- line therapy, patients can continue on induction therapy for as long as tumour shrinkage continues and the treatment is tolerable.
• Good practice point

Practice point
For patients receiving initial therapy with folinic acid, 5FU, oxaliplatin and irinotecan hydrochloride (FOLFOXIRI), with or without bevacizumab, a fluoropyrimidine plus bevacizumab may be considered as maintenance therapy (as was done in the pivotal trials examining FOLFOXIRI).

• Guidelines:Colorectal cancer/Treatment and continuum-of-care model#Practice_point_4
• For patients receiving initial therapy with folinic acid, 5FU, oxaliplatin and irinotecan hydrochloride (FOLFOXIRI), with or without bevacizumab, a fluoropyrimidine plus bevacizumab may be considered as maintenance therapy (as was done in the pivotal trials examining FOLFOXIRI).
• Good practice point

Practice point
For patients receiving initial therapy with a single-agent fluoropyrimidine (plus bevacizumab), induction therapy should be maintained.

• Guidelines:Colorectal cancer/Treatment and continuum-of-care model#Practice_point_5
• For patients receiving initial therapy with a single-agent fluoropyrimidine (plus bevacizumab), induction therapy should be maintained.
• Good practice point

Practice point
Initial induction therapy or a second-line therapy should be reintroduced at radiological or first signs of symptomatic progression.

• Guidelines:Colorectal cancer/Treatment and continuum-of-care model#Practice_point_6
• Initial induction therapy or a second-line therapy should be reintroduced at radiological or first signs of symptomatic progression.
• Good practice point

Practice point
If a second-line therapy is chosen, re introduction of the initial induction treatment should be a part of the entire treatment strategy as long as no relevant residual toxicity is present.

• Guidelines:Colorectal cancer/Treatment and continuum-of-care model#Practice_point_7
• If a second-line therapy is chosen, re introduction of the initial induction treatment should be a part of the entire treatment strategy as long as no relevant residual toxicity is present.
• Good practice point

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Systemic options for second-line treatment

Practice point
Patients who did not receive bevacizumab as part of first-line therapy should be considered for bevacizumab in second-line therapy, in combination with a second-line cytotoxic regimen.

• Guidelines:Colorectal cancer/Systemic options second-line treatment#Practice_point_1
• Patients who did not receive bevacizumab as part of first-line therapy should be considered for bevacizumab in second-line therapy, in combination with a second-line cytotoxic regimen.
• Good practice point

Practice point
Patients who received bevacizumab as part of the first-line regimen and have RAS wild-type (BRAF wild-type) metastatic colorectal cancer should be considered for combination EGFR monoclonal antibodies with FOLFIRI/irinotecan.

• Guidelines:Colorectal cancer/Systemic options second-line treatment#Practice_point_2
• Patients who received bevacizumab as part of the first-line regimen and have RAS wild-type (BRAF wild-type) metastatic colorectal cancer should be considered for combination EGFR monoclonal antibodies with FOLFIRI/irinotecan.
• Good practice point

Practice point
Patients who received a first-line oxaliplatin-containing regimen should be switched to an irinotecan-containing regimen, and vice versa.

• Guidelines:Colorectal cancer/Systemic options second-line treatment#Practice_point_3
• Patients who received a first-line oxaliplatin-containing regimen should be switched to an irinotecan-containing regimen, and vice versa.
• Good practice point

Practice point
Patients who experience disease progression during first-line 5FU monotherapy should be offered an irinotecan or oxaliplatin-containing regimen if they have adequate performance status.

• Guidelines:Colorectal cancer/Systemic options second-line treatment#Practice_point_4
• Patients who experience disease progression during first-line 5FU monotherapy should be offered an irinotecan or oxaliplatin-containing regimen if they have adequate performance status.
• Good practice point

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Systemic options for third-line treatment

Practice point
Patients with mCRC considering treatment in the third-line setting have limited therapeutic options and typically have reduced quality of life; therefore physicians must carefully balance any efficacy benefit associated with therapy with its toxicity profile.

• Guidelines:Colorectal cancer/Systemic options third-line treatment#Practice_point_1
• Patients with mCRC considering treatment in the third-line setting have limited therapeutic options and typically have reduced quality of life; therefore physicians must carefully balance any efficacy benefit associated with therapy with its toxicity profile.
• Good practice point

Practice point

Cetuximab or panitumumab treatment should be considered in patients with RAS wild-type and BRAF wild-type metastatic colorectal cancer not previously treated with these agents, taking into account the following: Cetuximab and Panitumumab are equally effective as single agents. Cetuximab in combination with irinotecan is more active than cetuximab alone in patients refractory to irinotecan with adequate performance status to receive combination therapy.

• Guidelines:Colorectal cancer/Systemic options third-line treatment#Practice_point_2
• Cetuximab or panitumumab treatment should be considered in patients with RAS wild-type and BRAF wild-type metastatic colorectal cancer not previously treated with these agents, taking into account the following:
• Cetuximab and Panitumumab are equally effective as single agents.
• Cetuximab in combination with irinotecan is more active than cetuximab alone in patients refractory to irinotecan with adequate performance status to receive combination therapy.
• Good practice point

Practice point
If available, regorafenib or trifluridine/tipiracil can be considered for patients with metastatic colorectal cancer refractory to all standard available therapies.

• Guidelines:Colorectal cancer/Systemic options third-line treatment#Practice_point_3
• If available, regorafenib or trifluridine/tipiracil can be considered for patients with metastatic colorectal cancer refractory to all standard available therapies.
• Good practice point

Practice point
Patients receiving third-line therapy should be offered participation in clinical trials, wherever available.

• Guidelines:Colorectal cancer/Systemic options third-line treatment#Practice_point_4
• Patients receiving third-line therapy should be offered participation in clinical trials, wherever available.
• Good practice point

Practice point
Symptom burden is often high in patients with mCRC especially as the disease progresses. Early palliative care intervention should be considered for all patients with mCRC as they can improve the quality of life of patients with cancer.

• Guidelines:Colorectal cancer/Systemic options third-line treatment#Practice_point_5
• Symptom burden is often high in patients with mCRC especially as the disease progresses. Early palliative care intervention should be considered for all patients with mCRC as they can improve the quality of life of patients with cancer.
• Good practice point

Follow-up after curative resection for colorectal cancer

Rationale for follow-up

Practice point
As there are no reliable indicators of an individual’s risk of synchronous or metachronous lesions, nor of treatable recurrence, all patients who have undergone curative surgery should be offered follow-up if they are fit for further intervention should disease be detected.

• Guidelines:Colorectal cancer/Rationale for follow-up#Practice_point_1
• As there are no reliable indicators of an individual’s risk of synchronous or metachronous lesions, nor of treatable recurrence, all patients who have undergone curative surgery should be offered follow-up if they are fit for further intervention should disease be detected.
• Good practice point

Practice point
Patients who are unfit for further surgery or who have advanced disease require appropriate follow-up directed at psychological support and symptom relief.

• Guidelines:Colorectal cancer/Rationale for follow-up#Practice_point_2
• Patients who are unfit for further surgery or who have advanced disease require appropriate follow-up directed at psychological support and symptom relief.
• Good practice point

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Optimal follow-up surveillance protocol

Evidence-based recommendation	Grade
Intensive follow-up after curative surgery for colorectal cancer should include CEA and CT scan, with the aim of early detection of recurrence or residual disease where there is the possibility for curative resection. PET/CT scan can be used as an effective adjunct for detection of recurrence, especially when the CEA and/or CT scans are suggestive of recurrence.	D

• Clinical question:Follow-up post curative CRC resection#Recommendation_1
• Intensive follow-up after curative surgery for colorectal cancer should include CEA and CT scan, with the aim of early detection of recurrence or residual disease where there is the possibility for curative resection.

PET/CT scan can be used as an effective adjunct for detection of recurrence, especially when the CEA and/or CT scans are suggestive of recurrence.

• Recommendation

Practice point
These recommendations apply only to asymptomatic patients. All patients who develop symptoms should be investigated rigorously.

• Clinical question:Follow-up post curative CRC resection#Practice_point_1
• These recommendations apply only to asymptomatic patients. All patients who develop symptoms should be investigated rigorously.
• Good practice point

Practice point
Colonoscopy should be performed at 12 months after surgery to exclude missed lesions. If the initial colonoscopy was incomplete then a colonoscopy should be performed at the latest 6 months after surgery. If the colonoscopy is normal, refer to the Clinical Practice Guidelines for Surveillance Colonoscopy for subsequent colonoscopies.

• Clinical question:Follow-up post curative CRC resection#Practice_point_2
• Colonoscopy should be performed at 12 months after surgery to exclude missed lesions. If the initial colonoscopy was incomplete then a colonoscopy should be performed at the latest 6 months after surgery. If the colonoscopy is normal, refer to the Clinical Practice Guidelines for Surveillance Colonoscopy for subsequent colonoscopies.
• Good practice point

Practice point
Intensive follow-up for colorectal cancer should be considered for patients who have had potentially curable disease, although optimal modality and frequency are yet to be firmly established.

• Clinical question:Follow-up post curative CRC resection#Practice_point_3
• Intensive follow-up for colorectal cancer should be considered for patients who have had potentially curable disease, although optimal modality and frequency are yet to be firmly established.
• Good practice point

Practice point
Intensive follow-up can detect recurrences earlier, thus surgical resection for curative intent is possible. However, this is not associated with improved survival.

• Clinical question:Follow-up post curative CRC resection#Practice_point_4
• Intensive follow-up can detect recurrences earlier, thus surgical resection for curative intent is possible. However, this is not associated with improved survival.
• Good practice point

Practice point
CEA and CT scans are readily accessible and relatively sensitive investigations.

• Clinical question:Follow-up post curative CRC resection#Practice_point_5
• CEA and CT scans are readily accessible and relatively sensitive investigations.
• Good practice point

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Health professionals performing follow-up and suggested follow-up schedule

Practice point
Follow-up can be delivered as a combination of visits to the surgeon or associated gasteroenterologist, with ongoing care by the GP and clinical nurse consultant.

• Guidelines:Colorectal cancer/Health professionals and follow up schedule#Practice_point_1
• Follow-up can be delivered as a combination of visits to the surgeon or associated gasteroenterologist, with ongoing care by the GP and clinical nurse consultant.
• Good practice point

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Pyschosocial care

Psychosocial care

Practice point
Patients with colorectal cancer should be screened for psychological distress at diagnosis and key points in their disease trajectory.

• Guidelines:Colorectal cancer/Psychosocial care#Practice_point_1
• Patients with colorectal cancer should be screened for psychological distress at diagnosis and key points in their disease trajectory.
• Good practice point

Practice point
Psychological interventions should be a component of colorectal cancer care, as they can improve the quality of life for patients with cancer.

• Guidelines:Colorectal cancer/Psychosocial care#Practice_point_2
• Psychological interventions should be a component of colorectal cancer care, as they can improve the quality of life for patients with cancer.
• Good practice point

Practice point
The use of decision aids should be considered for preference-sensitive decisions about treatment for colorectal cancer.

• Guidelines:Colorectal cancer/Psychosocial care#Practice_point_3
• The use of decision aids should be considered for preference-sensitive decisions about treatment for colorectal cancer.
• Good practice point

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A recommendation formulated after a systematic review of the evidence, indicating supporting references.

A recommendation formulated in the absence of quality evidence, after a systematic review of the evidence was conducted and failed to identify admissible evidence on the clinical question.

A recommendation on a subject that is outside the scope of the search strategy for the systematic review, based on expert opinion and formulated by a consensus process.

Measures to prevent the onset of disease. This may include prevention strategies to modify cancer risk factors, such as dietary and lifestyle interventions, and medical interventions to enhance resistance to the effects of exposure to a disease agent, such as chemoprevention and vaccines.

Referring to the large bowel, comprising the colon and rectum.

A common medication used to treat pain, fever, and inflammation. Also known as acetylsalicylic acid (ASA).

A type of bacteria that grows in the digestive tract.

Medication commonly used to manage the pain and inflammation.

A study in which people are allocated at random (by chance alone) to receive one of several clinical interventions. One of these interventions is the standard of comparison or control.

Medication used to slow down or prevent bone loss.

The National Bowel Cancer Screening Program. An Australian screening program that aims to reduce illness and death from bowel cancer through early detection or prevention of the disease.

A medical professional who treats acute and chronic illnesses and provides preventive care and health education to a wide range of patients.

A test that can detect microscopic amounts of blood in stools. Types of FOBT include immunochemical FOBTs (iFOBTs), which directly detect haemoglobin using antibodies specific for the globin moiety of human haemoglobin, and guaiac FOBTs (gFOBTs), which detect peroxidase activity, an indirect method for identification of haemoglobin.

An examination of the large bowel using a camera on a flexible tube, which is passed through the anus.

Performing tests to identify disease in people before any symptoms appear.

Also known as virtual colonoscopy, a medical imaging procedure that uses low dose radiation CT scanning to obtain an interior view of the colon (the large bowel) that is otherwise only seen with a more invasive procedure where an endoscope is inserted into the rectum and passed through the entire colon.

The surgical removal of all or part of the colon. The affected areas of the colon are cut out and the two ends are joined back together. Colectomies are named for the part removed. They include: right and left hemicolectomies, and transverse, sigmoid, subtotal and total colectomies.

Using scans, including nuclear medicine, to create images of the interior of a body for clinical analysis and medical intervention.

A system that describes the amount and spread of cancer in a patient’s body. T describes the size of the tumour and its spread into nearby tissue; N describes the spread to nearby lymph nodes and M describes metastasis (spread of cancer to other parts of the body).

A surgical procedure to remove the cancerous part of the lining of the abdominal cavity.

A treatment given with or shortly after another treatment to make it more effective. This usually refers to surgery followed by chemotherapy or radiotherapy.

Systemic chemotherapy using a combination of the drugs Leucovorin (folinic acid), Fluorouracil, and Oxaliplatin.

A type of treatment given as a first step to shrink a tumour before main treatment (usually surgery) is given.

Carcinoembryonic antigen. A protein that may be found in the blood of a person with colorectal cancer.

A computerised tomography (CT) scan, which x-ray equipment to create detailed digital images, or scans, of areas inside the body.

Cancer that has spread from the primary site of origin (where it started) into different area(s) of the body.

Anti-cancer drugs that are injected into a vein or given by mouth. These drugs travel through the bloodstream to all parts of the body.

5-fluorouracil is a systemic chemotherapy using fluorouracil.