Overview of evidence (non-systematic literature review)
No systematic reviews were undertaken for this topic. Practice points were based on selected published evidence. See Guidelines development process.
Where possible, preoperative radiation treatment is favoured over postoperative radiation treatment as several trials discussed previously, including the landmark German CAO/ARO/AIO-94 study, have shown that a neoadjuvant approach is more effective (less local recurrence) and less toxic, than postoperative delivery of radiation treatment. This approach would only ever be considered on an individual basis if preoperative radiation treatment (or chemoradiation) had not been delivered and pathological staging revealed unexpectedly higher-risk disease (T3 +/- N1-2, or R1 resection).
In ideal circumstances, preoperative discussion and review of clinical details and MRI imaging in a multidisciplinary setting should reduce the proportion of patients who then require postoperative radiotherapy. However, no test is 100% sensitive, so unexpected upstaging at the time of histopathological assessment does occur.
A meta-analysis of 8 randomised trials of 2157 patients shows that post-operative adjuvant radiotherapy significantly reduces the yearly risk of local recurrence by 37% compared to surgery alone (p=0.002).
The National Institute of Health (NIH) made a clinical announcement in 1991 about the benefits of a sequential regimen of 5-flurouracil based chemotherapy and radiation therapy in reducing overall tumour recurrence rates, local recurrence and prolong survival in patients with resected stage II and III rectal cancer. This was based on the results of the Krook trial in 204 patients demonstrating that a combination of post operative radiation with 5-FU and systemic therapy with a flurouracil based regimen reduced recurrence by 34% (p = 0.0016), local recurrence by 46% (p = 0.036) and distant metastasis by 37%(p = 0.01) and overall death rate by 29% (p = 0.025) compared to radiation alone. The INT0114 study of 1695 patients compared bolus 5FU alone, 5FU plus leucovorin, 5FU plus levamisole and 5FU plus leucovorin all with pelvic radiation post operatively. No difference in disease free survival or overall survival was seen.
INT861751 randomised 660 patients with high risk rectal cancer to post operative 5FU given by bolus or protracted venous infusion (PVI) during radiotherapy. PVI demonstrated an improved disease free survival and overall survival predominantly in reducing distant relapse. The subsequent large INT0144 study of 1917 patients however found no difference in relapse free survival or overall survival at 3 years for patients receiving post-operative pelvic radiotherapy with one of three adjuvant chemotherapy protocols: 1) bolus 5FU in two 5 day cycles before and after radiotherapy plus PVI 5FU during radiation, PVI 5FU 42 days before and 56 days after radiation and concurrent PVI 5FU or 3) bolus 5FU plus leucovorin in two 5 day cycles before and after radiation with bolus 5FU and levamisole. The PVI arm had a much lower haematological toxicity rate than the bolus arms.
|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.|
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.
- Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004 Oct 21;351(17):1731-40 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15496622.
- Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, et al. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol 2012 Jun 1;30(16):1926-33 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22529255.
- ColorectalReferring to the large bowel, comprising the colon and rectum. Cancer Collaborative Group.. Adjuvant radiotherapy for rectal cancer: a systematic overview of 8,507 patients from 22 randomised trials. Lancet 2001 Oct 20;358(9290):1291-304 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11684209.
- National Cancer Institute. Benefits of adjuvant therapy for rectal cancer. [homepage on the internet] US National Library of Medicine; 1991 Mar 13 [cited 2017 Jan 4]. Available from: https://www.nlm.nih.gov/databases/alerts/rectal_cancer.html.
- Krook JE, Moertel CG, Gunderson LL, Wieand HS, Collins RT, Beart RW, et al. Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med 1991 Mar 14;324(11):709-15 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/1997835.
- Tepper JE, O'Connell M, Niedzwiecki D, Hollis DR, Benson AB 3rd, Cummings B, et al. Adjuvant therapy in rectal cancer: analysis of stage, sex, and local control--final report of intergroup 0114. J Clin Oncol 2002 Apr 1;20(7):1744-50 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11919230.
- Smalley SR, Benedetti JK, Williamson SK, Robertson JM, Estes NC, Maher T, et al. Phase III trial of fluorouracil-based chemotherapy regimens plus radiotherapy in postoperative adjuvant rectal cancer: GI INT 0144. J Clin Oncol 2006 Aug 1;24(22):3542-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16877719.