Skip to main content
Log in

Morbidities of adjuvant chemotherapy and radiotherapy for resectable rectal cancer

An overview

  • Current Status
  • Published:
Diseases of the Colon & Rectum

Abstract

PURPOSE: Although adjuvant chemoradiotherapy may improve outcomes after surgery for high-risk rectal cancer, its toxicities are not well documented. This is a review of complications associated with adjuvant therapy in randomized, controlled trials. METHODS: A MEDLINE and literature search was performed for randomized, controlled trials of adjuvant therapy for rectal cancer. Modalities of adjuvant therapy evaluated included preoperative radiotherapy, preoperative chemoradiotherapy, postoperative radiotherapy, and postoperative chemoradiotherapy. All documented complications were analyzed, including any effect on pelvic floor function and quality of life. RESULTS: Short-term (acute) complications of preoperative radiotherapy include lethargy, nausea, diarrhea, and skin erythema or desquamation. These acute effects develop to some degree in most patients during treatment but are usually self-limiting. With preoperative radiotherapy the incidence of perineal wound infection increases from 10 to 20 percent. The acute toxicities after postoperative radiotherapy for rectal cancer occur in 4 to 48 percent of cases, and serious toxicities, requiring hospitalization or surgical intervention, occur in 3 to 10 percent of cases. Postoperative radiotherapy is associated with more complications than preoperative radiotherapy. The main problems with postoperative radiotherapy are small-bowel obstruction (5–10 percent), delay in starting radiotherapy caused by delayed wound healing (6 percent) and postoperative fatigue (14 percent), and toxicities precluding completion of adjuvant therapy (49–97 percent). The morbidity and mortality of both preoperative and postoperative radiotherapy are higher in elderly patients and when two-portal rather than three-portal or four-portal radiation technique is used. Meticulous radiation technique is important, and multiple fields of irradiation are mandatory. After combined adjuvant chemotherapy and radiotherapy acute hematologic and gastrointestinal toxic effects are frequent (5–50 percent). Delayed radiation toxicities include radiation enteritis (4 percent), small-bowel obstruction (5 percent), and rectal stricture (5 percent). Pelvic floor function and quality of life have not been well evaluated in randomized, controlled trials. CONCLUSION: Adjuvant therapy for rectal cancer has considerable adverse effects. Adverse effects on bowel and sphincter function and quality of life have not been defined.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Abulafi AM, Williams NS. Local recurrence of colorectal cancer: the problem, mechanisms, management and adjuvant therapy. Br J Surg 1994;817–9.

  2. Quirke P, Durdey P, Dixon MF, Williams NS. Local recurrence of rectal adenocarcinoma due to inadequate surgical resection: histopathological study of lateral tumour spread and surgical excision. Lancet 1986;2:996–8.

    Google Scholar 

  3. Minsky BD, Mies C, Recht A, Rich TA, Chaffey JT. Resectable adenocarcinoma of the rectosigmoid and rectum. Patterns of failure and survival. Cancer 1988;61:1408–16.

    Google Scholar 

  4. Rich J, Gunderson LL, Lew R, Galdibini JJ, Cohen AM, Donalson G. Patterns of recurrence of rectal cancer after potentially curative surgery. Cancer 1983;52:1317–29.

    Google Scholar 

  5. MacFarlane JK, Ryall RD, Heald RG. Mesorectal excision for rectal cancer. Lancet 1993;341:457–60.

    Google Scholar 

  6. Parker SL, Tong T, Bolden S, Wingo PA. Cancer statistics. CA Cancer J Clin 1997;1997;47:5–27.

    Google Scholar 

  7. Bosset JF, Horiot JC. Adjuvant treatment in the curative management of rectal cancer: a critical review of the results of clinical randomised trials. Eur J Cancer 1993;29A:770–4.

    Google Scholar 

  8. Casillas S, Pelley RJ, Milsom JW. Adjuvant therapy for colorectal cancer: present and future perspectives. Dis Colon Rectum 1997;40:977–92.

    Google Scholar 

  9. National Institute of Health Consensus Conference. Adjuvant therapy for patients with colon and rectal cancer. JAMA 1990;264:1444–50.

    Google Scholar 

  10. Wassif S. Ten years' experience with a multimodality treatment of advanced stages of rectal cancer. Cancer 1983;52:2017–24.

    Google Scholar 

  11. Smith D, Muff N, Shetabi H,et al. Postoperative adjuvant chemotherapy and radiotherapy for cancer of the large bowel and rectum. Am J Surg 1989;157:508–11.

    Google Scholar 

  12. Kemeny N, Lokich J, Anderson N,et al. Recent advances in the treatment of advanced colorectal cancer. Cancer 1993;1:9–18.

    Google Scholar 

  13. O'Connell M, Gunderson LL. Adjuvant therapy for adenocarcinoma of the rectum. World J Surg 1992;16:510–5.

    Google Scholar 

  14. Stearns MW Jr, Deddish MR, Quan SH, Leaming RH. Preoperative roentgen therapy for cancer of the rectum and rectosigmoid. Surg Gynecol Obstet 1974;138:584–6.

    Google Scholar 

  15. Kligerman MM. Preoperative radiation therapy in rectal cancer. Cancer 1975;36:691–5.

    Google Scholar 

  16. Higgins GA Jr, Conn JH, Jordan PH Jr, Humphrey EW, Roswit B, Keehn RJ. Preoperative radiotherapy for colorectal cancer. Ann Surg 1975;181:624–31.

    Google Scholar 

  17. Rider WD, Palmer JA, Mahoney LJ, Robertson CT. Preoperative irradiation in operable cancer of the rectum: report of the Toronto trial. Can J Surg 1977;20:335–8.

    Google Scholar 

  18. First Report of an MRC Working Party. A trial of preoperative radiotherapy in the management of operable rectal cancer. Br J Surg 1982;69:513–9.

    Google Scholar 

  19. Second Report of an MRC Working Party. The evaluation of low dose preoperative X-ray therapy in the management of operable rectal cancer: results of a randomly controlled trial. Br J Surg 1984;71:21–5.

    Google Scholar 

  20. Buchanan R. Cobalt on the way out [letter]. Br Med J 1986;292:290.

    Google Scholar 

  21. Cedermark B, Theve NO, Rieger A,et al. Preoperative short-term radiotherapy in rectal carcinoma: a preliminary report of a prospective randomized study. Cancer 1985;55:1182–5.

    Google Scholar 

  22. Higgins GA, Humphrey EW, Dwight RW, Roswit B, Lee LE Jr, Keehn RJ. Preoperative radiation and surgery for cancer of the rectum. Cancer 1986;58:352–9.

    Google Scholar 

  23. Gerard A, Buyse M, Nordlinger B,et al. Preoperative radiotherapy as adjuvant treatment in rectal cancer: final results of a randomised study of the European Organisation for Research and Treatment of Cancer (EORTC). Ann Surg 1988;208:606–14.

    Google Scholar 

  24. Reis Neto JA, Quilici FA, Reis JA Jr. A comparison of nonoperativevs. preoperative radiotherapy in rectal carcinoma: a 10-year randomized trial. Dis Colon Rectum 1989;32:702–10.

    Google Scholar 

  25. Stockholm Rectal Cancer Study Group. Preoperative short-term radiation therapy in operable rectal carcinoma: a prospective randomised trial. Cancer 1990;66:49–55.

    Google Scholar 

  26. Dahl O, Horn A, Morild I,et al. Low dose preoperative radiation postpones recurrences in operable rectal cancer: results of a randomised multicentre trial in Western Norway. Cancer 1990;66:2286–94.

    Google Scholar 

  27. Kerman HD, Roberson SH, Bloom TS,et al. Rectal carcinoma. Long-term experience with moderately high-dose preoperative radiation and low anterior resection. Cancer 1992;69:2813–9.

    Google Scholar 

  28. Frykholm GJ, Glimelius B, Påhlman L. Preoperative or postoperative irradiation in adenocarcinoma of the rectum: final treatment results of a randomized trial and an evaluation of late secondary effects. Dis Colon Rectum 1993;36:564–72.

    Google Scholar 

  29. Marsh PJ, James RD, Schofield PF. Adjuvant preoperative radiotherapy for locally advanced rectal carcinoma: results of a prospective, randomized trial. Dis Colon Rectum 1994;37:1205–14.

    Google Scholar 

  30. Goldberg PA, Nicholls RJ, Porter NH, Love S, Grimsey JE. Long-term results of a randomised trial of short-course low-dose adjuvant preoperative radiotherapy for rectal cancer: reduction in local treatment failure. Eur J Cancer 1994;30A:1602–6.

    Google Scholar 

  31. Medical Research Council Rectal Cancer Working Party. Randomised trial of surgery aloneversus radiotherapy followed by surgery for potentially operable locally advanced rectal cancer. Lancet 1996;348:1605–10.

    Google Scholar 

  32. Swedish Rectal Cancer Trial. Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med 1997;336:980–7.

    Google Scholar 

  33. Graf W, Dahlberg M, Osman MM, Holmberg L, Påhlman L, Glimelius B. Short term preoperative radiotherapy results in down-staging of rectal cancer: a study of 1316 patients. Radiother Oncol 1997;43:133–7.

    Google Scholar 

  34. Frykholm GJ, Sintorn K, Montelius A, Jung B, Påhlman L, Glimelius B. Acute lumbosacral plexopathy during and after preoperative radiotherapy of rectal adenocarcinoma. Radiother Oncol 1996;38:121–30.

    Google Scholar 

  35. Fletcher GH. Hypofractionation: lessons from complications. Radiother Oncol 1991;20:10–5.

    Google Scholar 

  36. Letschert JG, Lebesque JV, de Boer RW, Hart AA, Bartelink H. Dose-volume correlation in radiation-induced late small bowel complications: a clinical study. Radiother Oncol 1990;18:307–20.

    Google Scholar 

  37. Påhlman L, Glimelius B. Pre- and postoperative radiotherapy in rectal and rectosigmoid carcinoma: report from a randomized multicenter trial. Ann Surg 1990;211:187–95.

    Google Scholar 

  38. Påhlman L, Glimelius B. The value of adjuvant radio-(chemo)therapy for rectal cancer. Eur J Cancer 1995;31A: 1347–50.

    Google Scholar 

  39. Boulis-Wassif S, Gerard A, Loygue J, Camelot D, Buyse M, Duez N. Final results of a randomised trial on the treatment of rectal cancer with preoperative radiotherapy alone or in combination with 5-FU, followed by radical surgery. Trial of the EORTC Gastrointestinal Tract Cancer Cooperative Group. Cancer 1984;53:1811–8.

    Google Scholar 

  40. Hyams DM, Mamounas EP, Petrelli N,et al. A clinical trial to evaluate the worth of preoperative multimodality therapy in patients with operable carcinoma of the rectum: a progress report of National Surgical Adjuvant Breast and Bowel Project Protocol R-03. Dis Colon Rectum 1997;40:131–9.

    Google Scholar 

  41. Minsky BD, Cohen AM, Kemeny N,et al. Combined modality therapy of rectal cancer: decreased acute toxicity with the preoperative approach. J Clin Oncol 1992;10:1218–24.

    Google Scholar 

  42. Minsky BD, Cohen AM, Kemeny N,et al. Enhancement of radiation-induced downstaging of rectal cancer by fluorouracil and high dose leucovorin chemotherapy. J Clin Oncol 1992;10:79–84.

    Google Scholar 

  43. Minsky B, Cohen A, Euker W,et al. Preoperative 5-flu-orouracil, low-dose leucovorin, and concurrent radiation therapy for rectal cancer. Cancer 1994;73:273–80.

    Google Scholar 

  44. Minsky BD, Conti JA, Huang Y, Knopf K. Relationship of acute gastrointestinal toxicity and the volume of irradiated small bowel in patients receiving combined modality therapy for rectal cancer. J Clin Oncol 1995;13:1409–16.

    Google Scholar 

  45. Balslev I, Pedersen M, Teglbjaerg PS,et al. Postoperative radiotherapy in Dukes' B and C carcinoma of the rectum and rectosigmoid: a randomized multicenter study. Cancer 1986;58:22–8.

    Google Scholar 

  46. Thomas PR, Lindblad AS. Adjuvant postoperative radiotherapy and chemotherapy in rectal carcinoma: a review of the Gastrointestinal Tumour Study Group experience. Radiother Oncol 1988;13:245–52.

    Google Scholar 

  47. Fisher B, Wolmark N, Rockette H,et al. Postoperative adjuvant chemotherapy or radiation therapy for rectal cancer: results from the NSABP Protocol R-01. J Natl Cancer Inst 1988;80:21–9.

    Google Scholar 

  48. Mameghan H, Gray BN, de Zwart J,et al. Adjuvant postoperative radiotherapy in rectal cancer; results from the ANZ bowel cancer trial (Protocol 8202). Australas Radiol 1991;35:61–5.

    Google Scholar 

  49. Treurniet-Donker AD, van Putten WL, Wereldsma JC,et al. Postoperative radiation therapy for rectal cancer: an interim analysis of a prospective, randomized multicenter trial in the Netherlands. Cancer 1991;67:2042–8.

    Google Scholar 

  50. Cafiero F, Gipponi M, Di Somma C,et al. Adjuvant post-operative radiotherapy vs radiotherapy plus 5-FU and levamisole in patients with TNM stage II-III resectable rectal cancer. A phase III randomized clinical trial. Eur J Surg Oncol 1995;21:391–2.

    Google Scholar 

  51. Medical Research Council Rectal Cancer Working Party. Randomised trial of surgery aloneversus surgery followed by radiotherapy for mobile cancer of the rectum. Lancet 1996;348:1610–4.

    Google Scholar 

  52. 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;84:352–7.

    Google Scholar 

  53. Wither HR, Taylor JM, Marciejewski B. The hazard of accelerated tumor clonogenic repopulation during radiotherapy. Acta Oncol 1988;27:131–46.

    Google Scholar 

  54. Thomas PR, Lindblad AS, Stablein DM,et al. Toxicity associated with adjuvant postoperative therapy for adenocarcinoma of the rectum. Cancer 1986;57:1130–4.

    Google Scholar 

  55. Gastrointestinal Tumour Study Group. Prolongation of disease-free interval in surgically treated rectal carcinoma. N Engl J Med 1985;312:1465–72.

    Google Scholar 

  56. Krook JE, Moertel CG, Gunderson LL,et al. Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med 1991;324:709–15.

    Google Scholar 

  57. Gallanger MJ, Brereton HD, Rostock RA,et al. A prospective study of treatment techniques to minimize the volume of pelvic small bowel with reduction of acute and late effects associated with pelvic irradiation. Int J Radiat Oncol Biol Phys 1986;12:1565–1573.

    Google Scholar 

  58. Devereux DF, Kavanagh M, Feldman M,et al. Small bowel exclusion from the pelvis by a polyglycolic acid mesh sling. J Surg Oncol 1984;26:107–12.

    Google Scholar 

  59. Devereux DF, Chandler JJ, Eisenstat T, Zinkin L. Efficacy of an absorbable mesh in keeping the small bowel out of the human pelvis following surgery. Dis Colon Rectum 1988;31:17–21.

    Google Scholar 

  60. Dasmahapatra KS, Swaminathan AP. The use of a biodegradable mesh to prevent radiation-associated smallbowel injury. Arch Surg 1991;126:366–9.

    Google Scholar 

  61. Trimbos J, Snijders-Keiholz T, Peters A. Feasibility of the application of a resorbable polyglycolic-acid mesh (dexon mesh) to prevent complications of radiotherapy following gynaecological surgery. Eur J Surg 1991;157:281–4.

    Google Scholar 

  62. Freund H, Gunderson LL, Krause R, Fischer JE. Prevention of radiation enteritis after abdominoperineal resectio and radiotherapy. Surg Gynecol Obstet 1979;149:206–8.

    Google Scholar 

  63. Durig M, Steenblock U, Herberer M, Harder F. Prevention of radiation injuries to the small intestine. Surg Gynecol Obstet 1984;159:162–3.

    Google Scholar 

  64. Sparso BH, Maase HVD, Kristensen D,et al. Complications following postoperative combined radiation and chemotherapy in adenocarcinoma of the rectum and rectosigmoid: a randomized trial that failed. Cancer 1984;54:2363–6.

    Google Scholar 

  65. Gastrointestinal Tumour Study Group. Radiation therapy and fluorouracil with or without semustine for the treatment of patients with surgical adjuvant adenocarcinoma of the rectum. J Clin Oncol 1992;10:549–57.

    Google Scholar 

  66. 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;331:502–7.

    Google Scholar 

  67. 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. Br J Surg 1997;84:1130–5.

    Google Scholar 

  68. Chen FC, Mackay JR, Woods RJ, Collopy BT, Fink RJ, Guiney MJ. Early experience with postoperative adjuvant chemoradiation for rectal carcinoma: focus on morbidity. Aust N Z J Surg 1995;65:732–6.

    Google Scholar 

  69. Fazio VW, Fletcher J, Montgue D. Prospective study of the effect of resection of the rectum on male sexual function. World J Surg 1980;4:149–52.

    Google Scholar 

  70. Koukouras F, Tzoracoleftheraskis E, Androulakis J. Radical consequence in the sexuality of male patients operated for colorectal carcinoma. Eur J Surg Oncol 1991;17:285–8.

    Google Scholar 

  71. Giancarlo DB, Domenico T, Paolo N,et al. Sexual dysfunction in males following extensive colorectal surgery. Int Surg 1981;66:133–5.

    Google Scholar 

  72. Oki S, Masui H, Shimada H,et al. The survival and the local recurrence rates of cases of the autonomic nerve preserving operation for rectal cancer. J Jpn Soc Coloproctol 1992;45:1132–8.

    Google Scholar 

  73. Weinstein M, Roberts M. Sexual potency following surgery for rectal carcinoma: a follow up of 44 patients. Ann Surg 1977;185:295–300.

    Google Scholar 

  74. Balslev I, Harling H. Sexual dysfunction following operation for carcinoma of the rectum. Dis Colon Rectum 1983;26:785–8.

    Google Scholar 

  75. Morita T, Yamanaka Y, Kon M. Clinical study on post-operative sexual following autonomic nerve preserving operation for rectal cancer. Impotence 1992;7:130–1.

    Google Scholar 

  76. van Driel MF, Weyman-Schultz WC, van de Wiel HB,et al. Female sexual functioning after radical surgical treatment of rectal and bladder cancer. Eur J Surg Oncol 1993;19:183–7.

    Google Scholar 

  77. Poad D, Arnold EP. Sexual function after pelvic surgery in women. Aust N Z J Obstet Gynaecol 1994;34:471–4.

    Google Scholar 

  78. Lushbaugh CC, Casarett GW. The effects of gonadal irradiation in clinical radiation therapy: a review. Cancer 1976;37:1111–20.

    Google Scholar 

  79. Bines J, Oleske DM, Cobleigh MA. Ovarian function in premenopausal women treated with adjuvant chemotherapy for breast cancer. J Clin Oncol 1996;14:1718–29.

    Google Scholar 

  80. Dahlberg M, Glimelius B, Graf W, Påhlman L. Preoperative irradiation affects functional results after surgery for rectal cancer: results from a randomized study. Dis Colon Rectum 1998;41:543–51.

    Google Scholar 

  81. Birnbaum EH, Myerson RJ, Fry RD, Kodner IJ, Fleshman JW. Chronic effects of pelvic radiation therapy on anorectal function. Dis Colon Rectum 1994;37:909–15.

    Google Scholar 

  82. Birnbaum EH, Dreznik Z, Myerson RJ,et al. Early effect of external beam radiation therapy on the anal sphincter: a study using anal manometry and transrectal ultrasound. Dis Colon Rectum 1992;35:757–61.

    Google Scholar 

  83. Varma JS, Smith AN, Busuttil A. Correlation of clinical and manometric abnormalities of rectal function following chronic radiation injury. Br J Surg 1985;72:875–8.

    Google Scholar 

  84. Varma JS, Smith AN, Busuttil A. Function of the anal sphincters after chronic radiation injury. Gut 1986;27:528–33.

    Google Scholar 

  85. Varma JS, Smith AN. Anorectal function following coloanal sleeve anastomosis for chronic radiation injury to the rectum. Br J Surg 1986;73:285–9.

    Google Scholar 

  86. Iwamoto T, Nakahara S, Mibu R, Hotokezaka M, Nakano H, Tanaka M. Effect of radiotherapy on anorectal function in patients with cervical cancer. Dis Colon Rectum 1997;40:693–7.

    Google Scholar 

  87. Kollmorgen CF, Meagher AP, Wolff BG, Pemberton JH, Martenson JA, Iistrup DM. The long-term effect of adjuvant postoperative chemoradiotherapy for rectal carcinoma on bowel function. Ann Surg 1994;220:676–82.

    Google Scholar 

  88. Spitzer WO. State of science 1986: quality of life and functional status as target variables for research. J Chron Dis 1987;40:465–71.

    Google Scholar 

  89. Sprangers MA, Taal BG, Aaronson NK, te Velde A. Quality of life in colorectal cancer: stomavs. nonstoma patients. Dis Colon Rectum 1995;38:361–9.

    Google Scholar 

  90. Williams NS, Johnston D. The quality of life after rectal excision for low rectal cancer. Br J Surg 1983;70:460–2.

    Google Scholar 

  91. Aaronson NK, Ahmedzai S, Bergman B,et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 1993;85:365–76.

    Google Scholar 

  92. Guyatt GH, Bombardier C, Tugwell PX. Measuring disease specific quality of life in clinical trials. Can Med Assoc J 1986;134:889–95.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Dr. Ooi is supported in part by the Irene and Margaret Stewardson Charitable Trusts.

About this article

Cite this article

Ooi, B.S., Tjandra, J.J. & Green, M.D. Morbidities of adjuvant chemotherapy and radiotherapy for resectable rectal cancer. Dis Colon Rectum 42, 403–418 (1999). https://doi.org/10.1007/BF02236362

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02236362

Key words

Navigation