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Adjuvant therapy for resected rectal cancer

INTRODUCTION

Surgical resection is the cornerstone of curative therapy for rectal cancer. However, surgery alone provides a high cure rate only for patients with early stage disease. Following potentially curative resection, five-year survival rates are 80 to 90 percent for patients with stage I rectal cancer, while they are below 80 percent for those with stage II or III disease (table 1). (See "Approach to the long-term survivor of colorectal cancer", section on 'Prognosis and natural history'.)

Many randomized trials have attempted to improve the results of surgery alone through the addition of chemotherapy and radiation therapy (RT), both before and after surgery. RT has emerged as an important component of adjuvant therapy for rectal cancer because of the distinct patterns of failure following resection. In contrast to colon cancer, in which the failure pattern is predominantly distant metastases, the site of first failure in patients undergoing surgery for rectal cancer is equally distributed locally (ie, pelvis) and in distant sites (eg, liver, lung) [1].

The majority of early trials of combined modality therapy in rectal cancer evaluated postoperative RT with or without chemotherapy. More recently, focus has shifted to preoperative (neoadjuvant) application of combined chemoradiotherapy. Neoadjuvant rather than adjuvant chemoradiotherapy is preferred for patients with transmural (T3/4) (table 1) or node-positive tumors, particularly if they are low-lying within the rectum. Advantages of this approach include better local control, increased likelihood of sphincter saving surgery, and a lower risk of chronic anastomotic stricture. (See "Neoadjuvant chemoradiotherapy and radiotherapy for rectal cancer", section on 'Indications for neoadjuvant treatment'.)

Nevertheless, initial surgery is still utilized in clinical practice, especially for those patients whose preoperative local staging evaluation cannot distinguish between a cT2 or T3 tumor, and proximal cT3N0 tumors for which RT may not be recommended after a total mesorectal excision (TME). (See "Pretreatment local staging evaluation for rectal cancer" and "Neoadjuvant chemoradiotherapy and radiotherapy for rectal cancer", section on 'T1/2 and clinically node-positive' and "Neoadjuvant chemoradiotherapy and radiotherapy for rectal cancer", section on 'cT3N0 tumors' and 'Favorable risk rectal cancer' below.)

Postoperative (adjuvant) therapy for resected rectal cancer in patients who have not received neoadjuvant chemoradiotherapy will be reviewed here. Neoadjuvant treatment approaches for rectal cancer, the role of adjuvant chemotherapy in patients who have received neoadjuvant therapy, the preoperative staging evaluation, surgical management of rectal cancer, treatment of locally advanced unresectable or locally recurrent rectal cancer, and posttreatment follow-up after definitive treatment are discussed separately.

                                 

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Literature review current through: Nov 2014. | This topic last updated: Mar 18, 2014.
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References
Top
  1. Minsky BD, Mies C, Recht A, et al. Resectable adenocarcinoma of the rectosigmoid and rectum. I. Patterns of failure and survival. Cancer 1988; 61:1408.
  2. Rich T, Gunderson LL, Lew R, et al. Patterns of recurrence of rectal cancer after potentially curative surgery. Cancer 1983; 52:1317.
  3. Gunderson LL, Sosin H. Areas of failure found at reoperation (second or symptomatic look) following "curative surgery" for adenocarcinoma of the rectum. Clinicopathologic correlation and implications for adjuvant therapy. Cancer 1974; 34:1278.
  4. Colorectal Cancer Collaborative Group. Adjuvant radiotherapy for rectal cancer: a systematic overview of 8,507 patients from 22 randomised trials. Lancet 2001; 358:1291.
  5. Prolongation of the disease-free interval in surgically treated rectal carcinoma. Gastrointestinal Tumor Study Group. N Engl J Med 1985; 312:1465.
  6. Douglass HO Jr, Moertel CG, Mayer RJ, et al. Survival after postoperative combination treatment of rectal cancer. N Engl J Med 1986; 315:1294.
  7. Fisher B, Wolmark N, Rockette H, et al. Postoperative adjuvant chemotherapy or radiation therapy for rectal cancer: results from NSABP protocol R-01. J Natl Cancer Inst 1988; 80:21.
  8. Krook JE, Moertel CG, Gunderson LL, et al. Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med 1991; 324:709.
  9. Radiation therapy and fluorouracil with or without semustine for the treatment of patients with surgical adjuvant adenocarcinoma of the rectum. Gastrointestinal Tumor Study Group. J Clin Oncol 1992; 10:549.
  10. O'Connell MJ, Martenson JA, Wieand HS, et al. Improving adjuvant therapy for rectal cancer by combining protracted-infusion fluorouracil with radiation therapy after curative surgery. N Engl J Med 1994; 331:502.
  11. Tepper JE, O'Connell MJ, Petroni GR, et al. Adjuvant postoperative fluorouracil-modulated chemotherapy combined with pelvic radiation therapy for rectal cancer: initial results of intergroup 0114. J Clin Oncol 1997; 15:2030.
  12. Tveit KM, Guldvog I, Hagen S, et al. Randomized controlled trial of postoperative radiotherapy and short-term time-scheduled 5-fluorouracil against surgery alone in the treatment of Dukes B and C rectal cancer. Norwegian Adjuvant Rectal Cancer Project Group. Br J Surg 1997; 84:1130.
  13. Arnaud JP, Nordlinger B, Bosset JF, et al. Radical surgery and postoperative radiotherapy as combined treatment in rectal cancer. Final results of a phase III study of the European Organization for Research and Treatment of Cancer. Br J Surg 1997; 84:352.
  14. Boice JD Jr, Greene MH, Killen JY Jr, et al. Leukemia and preleukemia after adjuvant treatment of gastrointestinal cancer with semustine (methyl-CCNU). N Engl J Med 1983; 309:1079.
  15. NIH consensus conference. Adjuvant therapy for patients with colon and rectal cancer. JAMA 1990; 264:1444.
  16. Petersen SH, Harling H, Kirkeby LT, et al. Postoperative adjuvant chemotherapy in rectal cancer operated for cure. Cochrane Database Syst Rev 2012; 3:CD004078.
  17. Byfield JE, Calabro-Jones P, Klisak I, Kulhanian F. Pharmacologic requirements for obtaining sensitization of human tumor cells in vitro to combined 5-Fluorouracil or ftorafur and X rays. Int J Radiat Oncol Biol Phys 1982; 8:1923.
  18. Miller RC, Sargent DJ, Martenson JA, et al. Acute diarrhea during adjuvant therapy for rectal cancer: a detailed analysis from a randomized intergroup trial. Int J Radiat Oncol Biol Phys 2002; 54:409.
  19. Smalley SR, Benedetti JK, Williamson SK, et al. Phase III trial of fluorouracil-based chemotherapy regimens plus radiotherapy in postoperative adjuvant rectal cancer: GI INT 0144. J Clin Oncol 2006; 24:3542.
  20. Tepper JE, O'Connell M, Niedzwiecki D, et al. Adjuvant therapy in rectal cancer: analysis of stage, sex, and local control--final report of intergroup 0114. J Clin Oncol 2002; 20:1744.
  21. Schüller J, Cassidy J, Dumont E, et al. Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients. Cancer Chemother Pharmacol 2000; 45:291.
  22. Kovach JS, Beart RW Jr. Cellular pharmacology of fluorinated pyrimidines in vivo in man. Invest New Drugs 1989; 7:13.
  23. Hofheinz RD, Wenz F, Post S, et al. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol 2012; 13:579.
  24. Allegra CJ, Yothers G, O'Connell MJ, et al. Neoadjuvant therapy for rectal cancer. Mature results from NSABP R-04 (abstract). J Clin Oncol 32, 2014 (suppl 3; abstr 390). Abstract available online at http://meetinglibrary.asco.org/content/123227-143 (Accessed on February 07, 2014).
  25. Gieschke R, Burger HU, Reigner B, et al. Population pharmacokinetics and concentration-effect relationships of capecitabine metabolites in colorectal cancer patients. Br J Clin Pharmacol 2003; 55:252.
  26. Haller DG, Catalano PJ, Macdonald JS, et al. Phase III study of fluorouracil, leucovorin, and levamisole in high-risk stage II and III colon cancer: final report of Intergroup 0089. J Clin Oncol 2005; 23:8671.
  27. André T, Quinaux E, Louvet C, et al. Phase III study comparing a semimonthly with a monthly regimen of fluorouracil and leucovorin as adjuvant treatment for stage II and III colon cancer patients: final results of GERCOR C96.1. J Clin Oncol 2007; 25:3732.
  28. Benson AB, Catalan P, Meropol NJ, et al. ECOG E3201: Intergroup randomized phase III study of postoperative irinotecan, 5-fluorouracil (FU), leucovorin (LV) (FOLFIRI) vs. oxaliplatin, FU/LV (FOLFOX) vs FU/LV for patients with stage II/III rectal cancer receiving either preoperative or postoperative radiation (RT)/FU (abstract). J Clin Oncol 2006; 24:152s.
  29. Kalofonos HP, Bamias A, Koutras A, et al. A randomised phase III trial of adjuvant radio-chemotherapy comparing Irinotecan, 5FU and Leucovorin to 5FU and Leucovorin in patients with rectal cancer: a Hellenic Cooperative Oncology Group Study. Eur J Cancer 2008; 44:1693.
  30. Kim TW, Lee JH, Lee JH, et al. Randomized trial of postoperative adjuvant therapy in Stage II and III rectal cancer to define the optimal sequence of chemotherapy and radiotherapy: 10-year follow-up. Int J Radiat Oncol Biol Phys 2011; 81:1025.
  31. Meyerhardt JA, Tepper JE, Niedzwiecki D, et al. Impact of body mass index on outcomes and treatment-related toxicity in patients with stage II and III rectal cancer: findings from Intergroup Trial 0114. J Clin Oncol 2004; 22:648.
  32. Griggs JJ, Mangu PB, Anderson H, et al. Appropriate chemotherapy dosing for obese adult patients with cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 2012; 30:1553.
  33. Kollmorgen CF, Meagher AP, Wolff BG, et al. The long-term effect of adjuvant postoperative chemoradiotherapy for rectal carcinoma on bowel function. Ann Surg 1994; 220:676.
  34. Miller AR, Martenson JA, Nelson H, et al. The incidence and clinical consequences of treatment-related bowel injury. Int J Radiat Oncol Biol Phys 1999; 43:817.
  35. Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004; 351:1731.
  36. MacFarlane JK, Ryall RD, Heald RJ. Mesorectal excision for rectal cancer. Lancet 1993; 341:457.
  37. Kariv Y, Kariv R, Hammel JP, Lavery IC. Postoperative radiotherapy for stage IIIA rectal cancer: is it justified? Dis Colon Rectum 2008; 51:1459.
  38. Merchant NB, Guillem JG, Paty PB, et al. T3N0 rectal cancer: results following sharp mesorectal excision and no adjuvant therapy. J Gastrointest Surg 1999; 3:642.
  39. Bokey EL, Ojerskog B, Chapuis PH, et al. Local recurrence after curative excision of the rectum for cancer without adjuvant therapy: role of total anatomical dissection. Br J Surg 1999; 86:1164.
  40. Kapiteijn E, Marijnen CA, Nagtegaal ID, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 2001; 345:638.
  41. Akasu T, Moriya Y, Ohashi Y, et al. Adjuvant chemotherapy with uracil-tegafur for pathological stage III rectal cancer after mesorectal excision with selective lateral pelvic lymphadenectomy: a multicenter randomized controlled trial. Jpn J Clin Oncol 2006; 36:237.
  42. Willett CG, Badizadegan K, Ancukiewicz M, Shellito PC. Prognostic factors in stage T3N0 rectal cancer: do all patients require postoperative pelvic irradiation and chemotherapy? Dis Colon Rectum 1999; 42:167.
  43. Greene FL, Stewart AK, Norton HJ. New tumor-node-metastasis staging strategy for node-positive (stage III) rectal cancer: an analysis. J Clin Oncol 2004; 22:1778.
  44. Gunderson LL, Sargent DJ, Tepper JE, et al. Impact of T and N stage and treatment on survival and relapse in adjuvant rectal cancer: a pooled analysis. J Clin Oncol 2004; 22:1785.
  45. American Joint Committee on Cancer Staging Manual, 7th, Edge SB, Byrd DR, Compton CC, et al (Eds), Springer, New York 2010. p.143.
  46. Bleday R, Breen E, Jessup JM, et al. Prospective evaluation of local excision for small rectal cancers. Dis Colon Rectum 1997; 40:388.
  47. Garcia-Aguilar J, Shi Q, Thomas CR Jr, et al. A phase II trial of neoadjuvant chemoradiation and local excision for T2N0 rectal cancer: preliminary results of the ACOSOG Z6041 trial. Ann Surg Oncol 2012; 19:384.