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

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Systematic review evidence

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? (REC3)

A systematic review was performed to compare the effects of local resection (with or without radiotherapy or chemotherapy) and radical resection (with or without radiotherapy or chemotherapy) on outcomes including survival, local recurrence rates, quality of life, adverse events and stoma rates.

The search identified two relevant guidelines for which systematic reviews were conducted, published by the Belgian Health Care Knowledge Centre (KCE)[1] and the United Kingdom National Institute for Health and Care Excellence (NICE).[2] A systematic review was performed to update the search results with relevant literature published after the cut-off dates.

The KCE guideline[1] reported systematic reviews and meta-analyses of level III-1 evidence, each with a low risk of bias, examining the effects of local versus radical resections on early stage colorectal cancer related outcomes:[3][4]

  • a systematic review and meta-analysis comparing local resection with radical resection for patients with T1N0M0 rectal adenocarcinoma,[3] which included results (n = 2855) from twelve level III 2 observational studies and one level II randomised controlled trial (RCTA 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.)
  • a systematic review and meta-analysis comparing local excision with radical surgery after neoadjuvant chemoradiotherapy for rectal cancer,[4] which included six level III-2 observational studies and one level II RCTA 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..

Both these systematic reviews were reported as having a low risk of bias, with scores of 8,[3] and 9,[4] out of 11 on the AMSTAR risk of bias checklist.

Three level II RCTs[5][6][7] were also included in the KCE guideline review. One of these studies[5] was reported to be at high overall risk of bias. Assessment of bias was not reported for the other two RCTs.

The NICE guideline[2] reported four level III-1 observational studies comparing local versus radical resection strategies.[8][9][10][11] Two of these studies were reported as having a serious risk of bias,[8][9] one had a very serious risk of bias,[11] and one had no serious risk of bias.[10]

The updated systematic review of those undertaken for the KCE and NICE guidelines identified one additional systematic review and meta-analysis,[12] which included one RCTA 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. and six observational studies. This review had a low risk of bias.

The search strategy, inclusion and exclusion criteria, and quality assessment are described in detail in the Technical report.

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Overall survival

Two systematic reviews and meta-analyses included in the KCE guideline[1] reported the effects of resection type on mortality and survival outcomes. A meta-analysis of 12 observational studies (n = 2,855) reported that 5-year overall survival was significantly higher for local resection patients, compared with radical resection patients (relative risk [RR] 1.46; 95% CI 1.19 to 1.77, p = 0.0002), with RRs ranging from 0.11 to 2.87 reported by each included study for the comparison of local vs radical resections.[3]

In an analysis of seven pooled observational studies conducted in T1 patients, transanal endoscopic microsurgery was associated with a nonsignificant reduction in overall survival, compared with total mesorectal excision (odds ratio [OR] 0.87; 95% CI 0.55 to 1.38).[12]

A retrospective observational study in patients with T1 or T2 N0M0 rectal adenocarcinoma (n = 153),[13] reported that 3-year overall survival among T1 patients did not differ between local excision and total mesorectal excision groups (100%). Among T2 patients, there was a nonsignificant increase in 3-year overall survival in the total mesorectal excision group (90%), compared with the local excision group (76.9%).[13]

Overall, evidence showed mixed and mostly nonsignificant differences in survival and mortality rates between local and radical resection patients.

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Disease-free survival

One meta-analysis study[3] observed the radical resection as group having a significantly higher 5 year disease free survival in comparison to local resection group, (RR 1.54; CI 1.15-2.05, p=0.003). However, this effect may be explained by the increased use of local resection on tumours in the lower third of the rectum, which have poorer prognosis. One retrospective observational study[13] reported that, among T1 patients, local excision was associated with a nonsignificant reduction in 3-year disease-free survival, compared with total mesorectal excision (84.21% versus 94.9%). Among T2 patients, 3-year disease-free survival was significantly lower in the local excision group, compared with the total mesorectal excision group (61.5% versus 87.5%; p = 0.44).[13]

Other studies that reported disease-free survival[4][12] found only negligible differences between local and radical resection groups.

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Local recurrenceThe reappearance of cancer at a site that was previously treated and responded to therapy.

The majority of studies reported higher rates of local recurrence in the local resection group. One systematic review and meta-analysis[3] reported that local resection was associated with significantly higher rates of local recurrence than radical resection (RR 2.36; 95% CI 1.64 to 3.39). Another systematic review and meta-analysis[4] reported that local excision was associated with a nonsignificant increase in local recurrence, compared with radical excision (10.1% versus 8%; OR 1.29; 95% CI 0.72 to 2.31).

A RCTA 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. found that 5-year local recurrence rate did not differ significantly between transanal endoscopic microsurgery and total mesorectal excision groups for T1 stage patients (p = 0.94), but local recurrence was significantly higher in the transanal endoscopic microsurgery group than the total mesorectal excision (96.1% versus 94.7%; p = 0.035) for T2 patients.[8]

Both the KCE and NICE guidelines stated that there was no good evidence to suggest that local resection does not harm by leading to increased local recurrence or metastases.[1][2] Across the studies, there was generally no clear difference in recurrence rate between treatment groups, and local recurrence rates were low in both groups. The only exception was a large observational study of data from a cancer registry which reported that, among the subgroup of patients with T2 tumours, transanal endoscopic microsurgery was associated with a higher local recurrence rate than total mesorectal excision.[11]Back to top

Postoperative complications

The KCE guideline states that major post-operative complications and peri-operative deaths are less frequent following local resection than radical resection.[1] Only one systematic review and one RCTA 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. examined postoperative complications as an outcome, revealing two different findings.[3][6] The systematic review and meta-analysis reported that the risk of post-operative complications was significantly lower for the local resection group, compared with the radical resection group, both for the total number of all postoperative complications (RR 0.16; 95% CI 0.08 to 0.30) and for major postoperative complications (RR 0.20; 95% CI 0.10 to 0.41).[3] In contrast, a small (n=35) comparative study observed an equal percentage of minor and major postoperative complications in both endoluminal locoregional resection and total mesorectal excision groups.[6]

Stoma formation and quality of life

The KCE guideline states that the benefits of local resection are less blood loss, a lower rate of permanent stoma, and shorter hospital stay. A systematic review and meta-analysis reported that the rate of lower stoma formation was lower for local resection, compared with radical resection (RR 0.17: 95% CI 0.09 to 0.30).[3]Back to top

Evidence summary and recommendations

Evidence summary Level References
There is limited evidence comparing local versus radical excision for early-stage (T1 to T2) rectal cancer in the Australasian population. II,

III-1

[3], [4], [5], [7], [8], [10], [11], [12], [13]
Evidence for overall survival showed inconsistent and mostly nonsignificant differences in relation to survival and mortality rates between local and radical resection patients. II, III-1 [3], [4], [5], [7], [8], [10], [11], [12], [13]
There were negligible differences in disease-free survival rates between local and radical resection groups. II, III-1 [3], [4], [5], [7], [8], [10], [11], [12], [13]
Local recurrenceThe reappearance of cancer at a site that was previously treated and responded to therapy. rates were higher for patients undergoing local excision, compared with radical resection, particularly among those with T2 stage tumours.

Local recurrenceThe reappearance of cancer at a site that was previously treated and responded to therapy. rates did not differ between patients undergoing transanal endoscopic microsurgery and those undergoing transanal local excision.

II, III-1 [3], [4], [5], [7], [8], [10], [11], [12], [13]
The rate of distant metastases was similar between local excision and radical resection. II, III-1 [3], [4], [5], [7], [8], [10], [11], [12], [13]
Major postoperative complications and peri-operative mortality were less frequent following local resection than radical excision.

Operative blood loss, permanent stoma rate and hospital stay were all reduced with local excision, compared with radical resection.

II, III-1 [3], [4], [5], [7], [8], [10], [11], [12], [13]
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Evidence-based recommendationA recommendation formulated after a systematic review of the evidence, indicating supporting references.Question mark transparent.png 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
Evidence-based recommendationA recommendation formulated after a systematic review of the evidence, indicating supporting references.Question mark transparent.png 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
Evidence-based recommendationA recommendation formulated after a systematic review of the evidence, indicating supporting references.Question mark transparent.png Grade
For patients with T2 tumours, consider radical resection as the first option if they are fit for surgery.
C
Practice pointA 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.Question mark transparent.png

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.

Practice pointA 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.Question mark transparent.png

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

Practice pointA 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.Question mark transparent.png

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.

Practice pointA 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.Question mark transparent.png

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.

Considerations in making these recommendations

For local excision, the rate of local recurrence increases as the depth of tumour invasion increases from T1sm1 to T1sm2 to T1sm3 to T2. T1sm3 tumours are associated with a significant increase in local recurrence, so this tumour stage may be considered the tipping point for radical resection.

Accurate pathological assessment of the specimen requires that the specimen is removed as a single specimen, regardless of the technique used. Piecemeal resection, whether performed as a surgical resection via local excision, TEMS or TAMIS, or endoscopically through endoscopic submucosal dissection (ESD) or endoscopic mucosal resection (EMR), will result in a compromised specimen with respect to the ability to assess it pathologically.

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Health system implications

Clinical practice

The guidance will not change the way that care is currently organised.

Resourcing

Implementation of this recommendation would have no significant resource implications.

Barriers to implementation

No barriers to the implementation of this recommendation are foreseen.

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Discussion

Unresolved issues

The role of neoadjuvant or neoadjuvant radiotherapy, with or without chemotherapy, as an adjunct to local excision of early rectal cancer, remains undetermined.

Determination and individualisation of approach also remains uncertain and there is a lack of evidence to make a definitive decision.

Studies currently underway

No relevant current studies have been identified that would be expected to provide more evidence on this topic.

Future research priorities

Further high-level studies comparing local versus radical excision for early-stage rectal cancer could provide evidence about long-term survival and recurrence.

Next section: emergency management of malignant large bowel obstruction

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References

  1. 1.01.11.21.31.4 Peeters MVC, E.; Bielen, D. et al.. Guideline on the management of rectal cancer: update of capita selecta – Part 3: Local vs Radical resection for stage 1 tumours. Good Clinical Practice (GCP). KCE Reports 260. D/2016/10.273/11. Brussels: Belgian Health Care Knowledge Centre (KCE); 2016.; 2017 Nov 17.
  2. 2.02.12.2 National Institute for Health and Care Excellence. Colorectal cancer: The Diagnosis and Management of colorectal cancer. United Kingdom: National Institute for Health and Care Excellence; 2014.
  3. 3.003.013.023.033.043.053.063.073.083.093.103.113.123.133.14 Kidane B, Chadi SA, Kanters S, Colquhoun PH, Ott MC. Local resection compared with radical resection in the treatment of T1N0M0 rectal adenocarcinoma: a systematic review and meta-analysis. Dis ColonThe main part of the large bowel, which absorbs water and electrolytes from undigested food (solid waste). Its four parts are the ascending colon, transverse colon, descending colon and sigmoid colon. RectumThe final section of the large bowel, ending at the anus. 2015 Jan;58(1):122-40 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25489704.
  4. 4.004.014.024.034.044.054.064.074.084.094.10 Shaikh I, Askari A, Ourû S, Warusavitarne J, Athanasiou T, Faiz O. Oncological outcomes of local excision compared with radical surgery after neoadjuvant chemoradiotherapy for rectal cancer: a systematic review and meta-analysis. Int J ColorectalReferring to the large bowel, comprising the colon and rectum. Dis 2015 Jan;30(1):19-29 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25367179.
  5. 5.05.15.25.35.45.55.65.7 Chen YY, Liu ZH, Zhu K, Shi PD, Yin L. Transanal endoscopic microsurgery versus laparoscopic lower anterior resection for the treatment of T1-2 rectal cancers. Hepatogastroenterology 2013 Jun;60(124):727-32 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23159393.
  6. 6.06.16.2 Lezoche E, Baldarelli M, Lezoche G, Paganini AM, Gesuita R, Guerrieri M. Randomized clinical trial of endoluminal locoregional resection versus laparoscopic total mesorectal excision for T2 rectal cancer after neoadjuvant therapy. Br J Surg 2012 Sep;99(9):1211-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22864880.
  7. 7.07.17.27.37.47.57.6 Winde G, Nottberg H, Keller R, Schmid KW, Bünte H. Surgical cure for early rectal carcinomas (T1). Transanal endoscopic microsurgery vs. anterior resection. Dis ColonThe main part of the large bowel, which absorbs water and electrolytes from undigested food (solid waste). Its four parts are the ascending colon, transverse colon, descending colon and sigmoid colon. RectumThe final section of the large bowel, ending at the anus. 1996 Sep;39(9):969-76 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/8797643.
  8. 8.08.18.28.38.48.58.68.78.8 Lee W, Lee D, Choi S, Chun H. Transanal endoscopic microsurgery and radical surgery for T1 and T2 rectal cancer. Surg Endosc 2003 Aug;17(8):1283-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/12739119.
  9. 9.09.1 Lezoche E, Paganini AM, Fabiani B, Balla A, Vestri A, Pescatori L, et al. Quality-of-life impairment after endoluminal locoregional resection and laparoscopic total mesorectal excision. Surg Endosc 2014 Jan;28(1):227-34 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/24002918.
  10. 10.010.110.210.310.410.510.610.7 Palma P, Horisberger K, Joos A, Rothenhoefer S, Willeke F, Post S. Local excision of early rectal cancer: is transanal endoscopic microsurgery an alternative to radical surgery? Rev Esp Enferm Dig 2009 Mar;101(3):172-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19388797.
  11. 11.011.111.211.311.411.511.611.711.8 Saraste D, Gunnarsson U, Janson M. Local excision in early rectal cancer-outcome worse than expected: a population based study. Eur J Surg Oncol 2013 Jun;39(6):634-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23414776.
  12. 12.012.112.212.312.412.512.612.712.8 Lu JY, Lin GL, Qiu HZ, Xiao Y, Wu B, Zhou JL. Comparison of Transanal Endoscopic Microsurgery and Total Mesorectal Excision in the Treatment of T1 Rectal Cancer: A Meta-Analysis. PLoS One 2015;10(10):e0141427 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26505895.
  13. 13.013.113.213.313.413.513.613.713.813.9 Elmessiry MM, Van Koughnett JA, Maya A, DaSilva G, Wexner SD, Bejarano P, et al. Local excision of T1 and T2 rectal cancer: proceed with caution. ColorectalReferring to the large bowel, comprising the colon and rectum. Dis 2014 Sep;16(9):703-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/24787457.
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Appendices


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