Clinical question list

From Cancer Guidelines Wiki


This page lists the questions answered by systematic review and modelling. For full details about the reviews, including the inclusion and exclusion criteria, please see the Technical report.

Primary preventionMeasures 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. (section lead: Finlay Macrae)

Clinical Question PPR1:
What is the risk-benefit ratio for use of aspirin for prevention of colorectal cancer stratified by risk of colorectal cancer itself? (What is the optimal dose and frequency of administration?)

PICO Question PPR1:
In an asymptomatic population at average risk or increased risk of colorectal cancer, what is the cost-benefit ratio of prophylactic AspirinA common medication used to treat pain, fever, and inflammation. Also known as acetylsalicylic acid (ASA). use in reducing the mortality and incidence of colorectal cancer?

Population Intervention Comparator Outcomes Study Design
  • Asymptomatic western population at average risk of colorectal cancer, or
  • Populations at increased risk of colorectal cancer
Prophylactic aspirin use Placebo or no AspirinA common medication used to treat pain, fever, and inflammation. Also known as acetylsalicylic acid (ASA). use
  • ColorectalReferring to the large bowel, comprising the colon and rectum. cancer incidence
  • ColorectalReferring to the large bowel, comprising the colon and rectum. cancer mortality
  • Adverse effects
Systematic reviews of Level II evidence or randomised controlled trials.
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Population screening for colorectal cancer (section leads: James St. John and Hooi Ee)

Clinical Question PSC1:
Is population screening based on testing with (a) immunochemical FOBT (iFOBTA 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.), (b) flexible sigmoidoscopy, (c) colonoscopy, (d) CT colonographyAlso 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., (e) faecal biomarkers such as DNA (f) plasma biomarkers such as DNA (g) any combination of the above screening tests effective in reducing bowel cancer mortality rates, feasible, acceptable and a cost-effective method of screening for the target population? a) Is population screening starting at an earlier age more effective, feasible, acceptable and cost-effective, compared with starting at age 50 years? b) In population screening, do the harms outweigh the benefits if routine screening by any method is continued beyond the age of 75 years?

PICO Question PSC1a (ScreeningPerforming tests to identify disease in people before any symptoms appear. benefit):
In persons without a colorectal cancer diagnosis or symptoms that might indicate colorectal cancer, which screening modality (immunochemical FOBT, flexible sigmoidoscopy, colonoscopy, CT colonographyAlso 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., faecal or blood biomarkers, or any combinations) compared with no screening, reduces colorectal cancer mortality, or the incidence of metastases at diagnosis?

Population Intervention Comparator Outcomes
Persons without a colorectal cancer diagnosis or symptoms that might indicate colorectal cancer
  • Immunochemical FOBT, or
  • Flexible sigmoidoscopyA procedure used by physicians to examine the inner lining of the rectum, particularly the lower portion of the colon (unlike the colonoscopy that examines the entirety of the colon). It consists of a flexible tube that is approximately 60 cm long, a small light and a camera attached at the tip of the tube., or
  • ColonoscopyAn examination of the large bowel using a camera on a flexible tube, which is passed through the anus., or
  • Faecal biomarkers, or
  • Blood biomarkers, or
  • Any combinations.
No screening test
  • ColorectalReferring to the large bowel, comprising the colon and rectum. cancer specific mortality
  • MetastaticCancer that has spread from the primary site of origin (where it started) into different area(s) of the body. colorectal cancer diagnosis
PICO Question PSC1b (ScreeningPerforming tests to identify disease in people before any symptoms appear. test accuracy):

For persons without a colorectal cancer diagnosis or symptoms that might indicate colorectal cancer, which screening modality (immunochemical FOBT, flexible sigmoidoscopy, colonoscopy, faecal or blood biomarkers, or any combinations) performs best in detecting colorectal cancer, and how does the diagnostic performance change with family history, age, or gender?

Population Index Test 1 Index Test 2 Reference standard Outcomes
Persons without a colorectal cancer diagnosis or symptoms that might indicate colorectal cancer

(with a family history of colorectal cancer or no family history of colorectal cancer)

ScreeningPerforming tests to identify disease in people before any symptoms appear. for CRC with:
  • Immunochemical FOBT, or
  • Flexible sigmoidoscopyA procedure used by physicians to examine the inner lining of the rectum, particularly the lower portion of the colon (unlike the colonoscopy that examines the entirety of the colon). It consists of a flexible tube that is approximately 60 cm long, a small light and a camera attached at the tip of the tube.,
  • ColonoscopyAn examination of the large bowel using a camera on a flexible tube, which is passed through the anus., or
  • Faecal biomarkers, or
  • Blood biomarkers, or
  • Any combinations
An alternative screening test or no screening ColonoscopyAn examination of the large bowel using a camera on a flexible tube, which is passed through the anus. or long-term follow up Diagnostic performance related to advanced adenoma and colorectal cancer
PICO Question PSC1c (ScreeningPerforming tests to identify disease in people before any symptoms appear. cost effectiveness - modelling):

In persons without a colorectal cancer diagnosis or symptoms that might indicate colorectal cancer, what is the most cost-effective, feasible and acceptable screening modality (iFOBTA 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., flexible sigmoidoscopy, colonoscopy, CT colonographyAlso 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., faecal or blood biomarkers test, or any combinations) compared with no screening?

PICO Question PSC1d (ScreeningPerforming tests to identify disease in people before any symptoms appear. age - modelling):
Is population screening starting at an earlier age more effective and as feasible, acceptable and cost-effective as screening starting at age 50 years? In population screening, do the harms outweigh the benefits if routine screening is continued beyond the age of 75 years?

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The symptomatic patient (section lead: Jon Emery)

Clinical Question SPT1-2:
What signs/symptoms alone or in combination are most predictive of CRC and what is the optimal maximum time from referral to diagnosis and treatment (diagnostic interval)?

PICO SPT1-2a (signs/symptoms):
In symptomatic patients without a colorectal cancer diagnosis, what signs or symptoms (persistent changed bowel movements, persistent diarrhoea or constipation, unexplained rectal bleeding, general or localised abdominal pain, unexplained palpable abdominal or rectal mass, unexplained weight loss, iron deficient anaemia, tiredness, fatigue, or any combination) correlate best with a diagnosis of colorectal cancer?

Population Signs/Symptoms Outcomes
Patients without colorectal cancer diagnosis presenting with symptoms of colorectal cancer Signs or symptoms alone or in combination:
  • persistent changed bowel movements
  • persistent diarrhoea or constipation
  • unexplained rectal bleeding
  • general or localised abdominal pain
  • unexplained palpable abdominal or rectal mass
  • unexplained weight loss
  • iron-deficient anaemia
  • tiredness or fatigue
  • rectal or anal pain
  • Diagnosis of colorectal cancer
  • Specificity
  • Sensitivity
  • Positive predictive valueA measure for the likelihood (probability) that the subject with a positive screening result has the disease being tested for.
  • Negative predictive value
  • AUC of ROC
Clinical Question SPT1-2:

What signs/symptoms alone or in combination are most predictive of CRC and what is the optimal maximum time from referral to diagnosis and treatment (diagnostic interval)?

PICO Question SPT1-2b (diagnostic interval):
In symptomatic patients without a colorectal cancer diagnosis, what is the optimal maximum diagnostic interval that achieves better than or equivalent outcomes in terms of survival, mortality, and diagnosis of metastatic disease?

Population Intervention Comparator Outcomes
Symptomatic patients without a colorectal cancer diagnosis The time delay between presentation with symptoms associated with colorectal cancer and treatment for colorectal cancer An alternative delay, or immediate treatment
  • 3-year survival, or
  • 5-year survival, or
  • ColorectalReferring to the large bowel, comprising the colon and rectum. cancer mortality
  • MetastaticCancer that has spread from the primary site of origin (where it started) into different area(s) of the body. disease at diagnosis

Risk and screening based on family history (section lead: Mark Jenkins)

Clinical Question FHS2:
What is the strength of association between family history and colorectal cancer risk and how do these associations vary by, number of affected relatives and degree of relatedness and age and sex of affected relatives and by the age and sex of the at-risk person?

PICO Question FSH2:
For individuals, has a family history of colorectal cancer been shown to be reliably associated with an increase in risk of occurrence of or death from colorectal cancer when compared to individuals who do not have a family history of colorectal cancer?

Population Exposure Comparator/ Reference group Outcomes
Persons without a colorectal cancer diagnosis or symptoms that might indicate colorectal cancer Presence of a family history of colorectal cancer No known family history of colorectal cancer
  • ColorectalReferring to the large bowel, comprising the colon and rectum. cancer mortality
  • ColorectalReferring to the large bowel, comprising the colon and rectum. cancer diagnosis
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PathologyA medical specialty that determines the cause and nature of diseases by examining and testing body tissues, for instance from laboratory examination of samples of body tissue. and staging (section leads: Charles Chan and Pierre Chapuis)

Clinical Question PTH1:
What is the optimal molecular profiling of colorectal cancer?

PICO Question PTH1:
In patients diagnosed with colorectal cancer who have undergone surgical resection or biopsy of the primary colorectal tumour, which molecular marker (BRAF/KRAS/NRAS/DNA mismatch repair /microsatellite instability) best predicts response to surgery, or adjuvant therapy or radiotherapy (disease-free survival, overall survival, disease-specific mortality, overall mortality, or relapse incidence)?

Population Prognostic factor Outcomes
Patients diagnosed with colorectal cancer and have had resection of the primary tumour

(any age, with or without a family history of CRC, or any stage of CRC including M1)

Any single prognostic marker (or any combination) examined in the primary resected colorectal cancer tumour tissue:
Immunohistochemical markers:

BRAF
Mismatch repair enzymes (MLH1, MSH2, PMS2, MSH6)
PCR markers:
BRAF
Microsatellite instability (which loci?)
KRAS
NRAS

Response to surgery, or adjuvant therapy or radiotherapy, including:
  • disease-free survival
  • overall survival
  • disease-specific mortality
  • overall mortality
  • relapse incidence
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Preparation for surgery and peri-operative optimisation (section lead: Elizabeth Murphy)

Clinical Question PRP2-5, 7:
Can peri operative management be optimised?

PICO Question PRP2-5, 7:
In patients diagnosed with colorectal cancer and undergoing surgical tumour resection, does mechanical bowel preparation with or without antibiotic prophylaxis, when compared to usual care, achieve better outcomes in terms of anastomotic leakage, surgical site infection, length of hospital stay and ileus?

Population Intervention Comparator Outcomes
Patients diagnosed with colorectal cancer and undergoing surgical tumour resection of curative intent Either:
  1. Mechanical bowel preparation with oral and intravenous antibiotic prophylaxis or
  2. Mechanical bowel preparation and intravenous antibiotic prophylaxis or
  3. Mechanical bowel preparation and oral antibiotic prophylaxis
No mechanical bowel preparation
  • Anastomotic leakage/dehiscence rates
  • Rate of surgical site/wound infection
  • Length of hospital stay
  • Ileus
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Elective and emergency surgery for colon and rectal cancer

Clinical Question COL1-2a and b:
What is the optimal approach to resection of colorectal cancers?

PICO Question COL1-2a (section lead: Andrew Luck):
In patients diagnosed with colon cancer, what is the optimal resection strategy to achieve the best outcomes in terms of length and quality of life?

Population Intervention Comparator Outcomes
Patients diagnosed with colon cancer and undergoing tumour resection Laparoscopic colon resection Open colon resection (colectomy)
  • ColorectalReferring to the large bowel, comprising the colon and rectum. cancer mortality
  • Perioperative morbidity
  • Perioperative mortality
  • Length of hospital stay
  • Post-op time to return of bowel function
  • Length of operation
  • Quality of life
  • Adverse events
PICO Question COL1-2b (section lead: Alexander (Sandy) Heriot):

In patients diagnosed with rectal cancer, what is the optimal resection strategy to achieve the best outcomes in terms of length and quality of life?

Population Intervention Comparator Outcomes
Patients diagnosed with rectal cancer and undergoing tumour resection
  • PolypectomyThe removal of polyps from the bowel.
  • Local transanal resectionThe local resection of tumour through the anus.
  • Transanal endoscopic microsurgery
  • Total mesorectal excisionA procedure used in the treatment of colorectal cancer in which a significant length of the bowel around the tumour is removed.
  • Abdominoperineal resectionAn operation for rectal cancer. This involves removing part of the colon, and the rectum and anus, and creating a permanent colostomy.
  • Anterior resectionA surgical procedure to remove cancer in the rectum with the bowel being re-joined to leave a functioning anus.
  • Laparoscopic resection
  • Open resection
An alternative resection strategy
  • ColorectalReferring to the large bowel, comprising the colon and rectum. cancer mortality
  • 30-day mortality rate
  • Perioperative mortality
  • 2-year survival
  • 5-year survival
  • Local recurrenceThe reappearance of cancer at a site that was previously treated and responded to therapy. rate
  • Perioperative morbidity
  • Permanent stoma rate
  • Quality of life
  • Adverse events
Clinical Question REC3:

What is the most effective treatment for early rectal cancer?

PICO Question REC3 (section lead: Alexander (Sandy) Heriot):
In patients diagnosed with stage I-II rectal cancer, what is the most effective treatment strategy to achieve the best outcomes in terms of length and quality of life?

Population Intervention Comparator Outcomes
Patients diagnosed with localised stage I-II potential resectable rectal cancer (nodal status unknown) Local resection with or without radiotherapy or chemotherapy Radical resection with or without radiotherapy or chemotherapy
  • Overall survival
  • 30-day survival
  • Local recurrenceThe reappearance of cancer at a site that was previously treated and responded to therapy. (positive nodes or margins)
  • Rectal cancer mortality
  • Quality of life
  • Adverse events
  • Stoma rates
Clinical Question COLMNG5:

What are the benefits of stenting or colostomy vs. acute resection with primary anastomosis in acute obstruction due to left-sided colon or rectal carcinoma?

PICO Question COLMNG5 (section leads: Alexander (Sandy) Heriot and Andrew Luck):
In patients diagnosed with colorectal cancer and acute obstruction, does stenting or colostomy achieve equivalent or better outcomes compared to acute resection with primary anastomosis?

Population Intervention Comparator Outcomes
Patients diagnosed with colorectal cancer and acute obstruction (due to left-side colon cancer or rectal cancer)
  • Stenting, or
  • Colostomy, or
  • Hartmann’s procedure
Acute surgical resection with primary anastomosis
  • Perioperative mortality
  • Perioperative morbidity
  • 5 year survival
  • Cancer specific survival
  • Length of hospital stay
  • Stoma rate (temporary or permanent)
  • Quality of life
  • Adverse events
Clinical Question COLMNG3: (Section leads: Cherry Koh and Andrew Luck)

What is the role for peritonectomy with or without PIC in the treatment recurrent as well as primary colorectal cancer with peritoneal involvement (not including appendiceal neoplasia)?

PICO Question COLMNG3 (Section leads: Cherry Koh and Andrew Luck):
For patients diagnosed with colorectal cancer and peritoneal involvement or isolated peritoneal recurrence of colorectal cancer, does peritonectomy, with or without perioperative intraperitoneal chemotherapy (PIC), achieve better outcomes in terms of length and quality of life than usual care?

Population Intervention Comparator Outcomes
Patients diagnosed with colorectal cancer and peritoneal involvement or isolated peritoneal recurrence of colorectal cancer PeritonectomyA surgical procedure to remove the cancerous part of the lining of the abdominal cavity. with or without HIPEC Usual care (systemic chemotherapy)
  • ColorectalReferring to the large bowel, comprising the colon and rectum. cancer specific mortality
  • 30-day mortality
  • 5-year survival
  • Quality of life
  • Adverse events
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Adjuvant therapyA treatment given with or shortly after another treatment to make it more effective. This usually refers to surgery followed by chemotherapy or radiotherapy. for colon cancer (section lead: Peter Gibbs)

Clinical Question ADJ1:
What is the efficacy of adjuvant combination chemotherapy in elderly patients with colon cancer?

PICO Question ADJ1:
In elderly patients (≥70 years) diagnosed with colon cancer, what is the efficacy of surgery and adjuvant combination chemotherapy (involving either 5-flurouracil or capecitabine combined with oxaliplatin), compared to surgery with a single chemotherapeutic agent (fluoropyrimidine based) in achieving the best outcomes in terms of colorectal cancer mortality, recurrence, quality of life and adverse effects?

Population Intervention Comparator Outcomes
Elderly patients diagnosed with colon cancer (≥70 years) Surgery in combination with one of the following:
  • Chemotherapy (either 5-Fluoruracil, Capecitabine, or Oxaliplatin)

AND an additional adjuvant chemotherapy drug (either 5-fluoruracil, capecitabine, or oxaliplatin)

Surgery with a single chemotherapeutic agent (Fluoropyrimidine based).
  • ColorectalReferring to the large bowel, comprising the colon and rectum. cancer mortality
  • ColorectalReferring to the large bowel, comprising the colon and rectum. recurrence
  • Quality of life
  • Adverse events
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Neo-adjuvant and adjuvant therapy for rectal cancer (section leads: Desmond Yip and Kathryn Field)

Clinical Question NEO1a-b:
Which patients with rectal cancer stage I-II could be considered for definitive chemoradiotherapy (no surgery), neo-adjuvant chemoradiotherapy or surgery alone?
a) What is the optimal timing for surgery after neoadjuvant therapy?
b) Should they be restaged?
PICO Question NEO1b:
For patients diagnosed with stage I-III rectal cancer, for which patients does neoadjuvant treatment (short or long course chemoradiotherapy) with surgery achieve equivalent or better outcomes in terms of length and quality of life than surgery alone?

Population Intervention Comparator Outcomes
Patients diagnosed with stage I-III rectal cancer Surgery without neoadjuvant therapy Short/long course chemoradiotherapy with surgery
  • Rectal cancer mortality
  • 30-day mortality
  • Distant metastases
  • Disease-free survival
  • Overall survival
  • Local recurrenceThe reappearance of cancer at a site that was previously treated and responded to therapy.
  • Quality of life
  • Sexual dysfunction
  • Adverse events
  • Rehospitalisation
  • Permanent stoma formation
  • Return to normal bowel function
PICO Question NEO1a:

For patients diagnosed with stage I-III rectal cancer, for which patients does neoadjuvant treatment (short or long course chemoradiotherapy) with surgery achieve equivalent or better outcomes in terms of length and quality of life than neoadjuvant chemoradiotherapy alone?

Population Intervention Comparator Outcomes
Patients diagnosed with stage I-III rectal cancer Definitive neoadjuvant chemoradiotherapy Neoadjuvant chemoradiotherapy with surgery
  • Rectal cancer mortality
  • 30-day mortality
  • Distant metastases
  • Disease-free survival
  • Overall survival
  • Local recurrenceThe reappearance of cancer at a site that was previously treated and responded to therapy.
  • Quality of life
  • Sexual dysfunction
  • Adverse events
  • Rehospitalisation
  • Permanent stoma formation
  • Return to normal bowel function
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Management of resectable locally recurrent disease and metastatic disease (section lead: Cherry Koh)

Clinical Question MNG13:
Which patients with locally recurrent colon or rectal cancer are more suitable for curative surgery?

PICO Question MNG13:
In patients with locally recurrent colon or rectal cancer, what is the role of curative surgery (+/- chemotherapy +/- radiotherapy) when compared to surgical palliation +/- palliative chemotherapy +/- palliative radiotherapy or other palliative interventions in terms of outcomes (overall survival, disease free survival, quality of life and complications)?

Population Intervention Comparator Outcomes
Patients diagnosed with locally recurrent colon or rectal cancer Curative surgery with or without chemotherapy, with or without radiotherapy Surgical palliation with or without palliative chemotherapy or radiotherapy and/or palliative care
  • Overall survival
  • Disease-free survival
  • Quality of life
  • Complications
Clinical Question MNG14:

Which patients with resectable synchronous or metachronous metastatic colon or rectal cancer are suitable for curative surgery?

PICO Question MNG14:
In patients with resectable synchronous or metachronous metastatic colorectal cancer, what is the role of surgical resection +/- chemotherapy when compared to non-surgical /palliative interventions in terms of outcomes (overall survival, disease free survival, progression free survival, quality of life and complications?)

Population Intervention Comparator Outcomes
Patients diagnosed with metastatic colon or rectal cancer and synchronous or metachronous resectable metastases
  • Curative surgery
  • With or without chemotherapy
  • With or without radiotherapy
Non-surgical (chemotherapy, radiotherapy, etc) and/or palliative care
  • Overall survival
  • Disease-free survival
  • Quality of life
  • Complications
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Management of non-resectable locally recurrent disease and metastatic disease (section lead: Louise Nott)

Clinical Question MNG16:
What is the impact of different liver directed therapies in patients with incurable metastatic colorectal cancer?

PICO Question MNG16:
In patients with incurable metastatic colorectal cancer, what are the effects of liver-directed therapies on survival and quality-of-life outcomes, compared with standard care?

Population Intervention Comparator Outcomes
Patients with metastatic incurable colorectal cancer
  • Liver directed therapies involving:
  • Trans-arterial (chemo) embolization, or
  • Hepatic intra-arterial infusion, or
  • Stereotactic radiotherapy, or
  • Radiofrequency ablation
  • Radioembolization in particular SIR-Spheres
Standard care (no therapy or, systemic chemotherapy with or without biologic surgery)
  • ColorectalReferring to the large bowel, comprising the colon and rectum. cancer mortality, or
  • Survival (progression free or overall), or
  • Quality of life, or
  • Adverse events, or
  • Surgical resection rate
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Follow up after curative resection for colorectal cancer (section lead: Peter Lee)

Clinical Question FUR1-2:
What is the optimal intensity of follow up post curative resection of colorectal cancer? And where?

PICO Question FUR1-2a:
In patients who have had curative resection of colorectal cancer, what surveillance protocol achieves the best outcomes in terms of detected recurrent disease, 5-year survival, quality of life, and colorectal cancer-related mortality?

Population Intervention Comparator Outcomes
Patient who have had curative resection of colorectal cancer Follow-up including:
  • Sigmoidoscopy, or
  • Serum CEACarcinoembryonic antigen. A protein that may be found in the blood of a person with colorectal cancer. test, or
  • ImagingUsing scans, including nuclear medicine, to create images of the interior of a body for clinical analysis and medical intervention. (CT scanA computerised tomography (CT) scan, which x-ray equipment to create detailed digital images, or scans, of areas inside the body.), or
  • Chest X-ray, or
  • FOBT, or
  • Ultrasonographic screening
An alternative follow-up modality
  • ColorectalReferring to the large bowel, comprising the colon and rectum. cancer mortality, or
  • Recurrence rates, or
  • Rate of curative resection following recurrence, or
  • Time to recurrence, or- 5 year survival, or
  • Quality of life
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