Skip to main content

Advertisement

Log in

Neoadjuvant therapy for adenocarcinoma of the rectum: Tumor response and acute toxicity

  • Original Contributions
  • Published:
Diseases of the Colon & Rectum

Abstract

PURPOSE: This study was designed to evaluate the down-staging effect and acute toxicity of preoperative radiation and chemoradiation for primary adenocarcinoma of the rectum. METHODS: The results of pretreatment staging with transrectal ultrasound and computed tomography were compared with final histologic stage in 260 consecutive patients who underwent neoadjuvant therapy and proctectomy for primary adenocarcinoma of the rectum. Patients underwent short-course radiation (2,000 cGy in five fractions), long-course radiation (4,500 cGy in 25 fractions), or chemoradiation (4,500 cGy in 25 fractions with concurrent chemotherapy). RESULTS: Down-staging of one or more T stages occurred in 116 of 260 (45 percent) patients overall (short-course radiation 34/82 (42 percent), long-course radiation 55/122 (45 percent), chemoradiation 27/56 (48 percent),P = not significant). Down-staging of one or more N stages occurred in 85 of 178 (48 percent) patients overall (short-course radiation 12/45 (27 percent), long-course radiation 49/86 (57 percent), chemoradiation 24/47 (51 percent),P=0.003). Complete pathologic response was observed in 16 of 260 (6 percent) patients overall (short-course radiation 4/82 (5 percent), long-course radiation 5/122 (4 percent), chemoradiation 7/56 (13 percent),P=0.08). Resection with negative margins (distal, proximal, and radial) was achieved in 211 of 227 patients (93 percent) in whom complete radial margin data were available. Permanent stomas were created in 35 percent of patients; temporary stomas were created in 15 percent. Thirty-three Grade 3 or 4 toxicities occurred in 22 of 260 (8 percent) patients overall during neoadjuvant therapy. Toxicity was more frequent in patients receiving chemoradiation (14/56; 25 percent) and long-course radiation (8/122; 7 percent) than in those receiving short-course radiation (0/82; 0 percent),P<0.0001. Perioperative complications occurred in 93 patients overall (36 percent). The postoperative mortality rate was 0.4 percent (1/260). There was no significant difference in the complication rate between patients treated with short-course radiation (26/82; 32 percent), long-course radiation (46/122; 36 percent), and chemoradiation (21/56; 38 percent). CONCLUSION: Neoadjuvant therapy for adenocarcinoma of the rectum is well tolerated and can produce substantial down-staging and a high curative resection rate. Chemoradiation can achieve high complete pathologic response rates, although toxicity during neoadjuvant therapy is greater than for radiation alone. Short-course radiation can achieve down-staging of both T stage and N stage.

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. Gastrointestinal Tumor Study Group. Prolongation of the disease-free survival in surgically treated rectal carcinoma. N Engl J Med 1985;12:1565–73.

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  6. Fleshman JW, Myerson RJ. Adjuvant radiation therapy for adenocarcinoma of the rectum. Surg Clin North Am 1997;77:15–25.

    Article  PubMed  Google Scholar 

  7. 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.

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  9. 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;80:21–9.

    PubMed  Google Scholar 

  10. Holm T, Johansson H, Cedermark B, Ekelund G, Rutqvist LE. Influence of hospital- and surgeon-related factors on outcome after treatment of rectal cancer with or without preoperative radiotherapy. Br J Surg 1997;84:657–63.

    Article  PubMed  Google Scholar 

  11. Porter GA, Soskolne CL, Yakimets WW, Newman SC. Surgeon-related factors and outcome in rectal cancer. Ann Surg 1998;227:157–67.

    Article  PubMed  Google Scholar 

  12. Dahlberg M, Pahlman L, Bergstrom R, Glimelius B. Improved survival in patients with rectal cancer: a population-based register study. Br J Surg 1998;85:515–20.

    Article  PubMed  Google Scholar 

  13. McCall JL. Total mesorectal excision: evaluating the evidence. Aust N Z J Surg 1997;67:599–602.

    PubMed  Google Scholar 

  14. Heald RJ, Ryall RD. Recurrence and survival after total mesorectal excision for rectal cancer. Lancet 1986;1:1479–82.

    Article  PubMed  Google Scholar 

  15. Heald RJ, Moran BJ, Ryall RD, Sexton R, MacFarlane JK. Rectal cancer: the Basingstoke experience of total mesorectal excision, 1978–1997. Arch Surg 1998;133:894–9.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  17. Enker WE, Thaler HT, Cranor ML, Polyak T. Total mesorectal excision in the operative treatment of carcinoma of the rectum. J Am Coll Surg 1995;181:335–46.

    PubMed  Google Scholar 

  18. Arenas RB, Fichera A, Mhoon D, Michelassi F. Total mesenteric excision in the surgical treatment of rectal cancer: a prospective study. Arch Surg 1998;133:608–11.

    Article  PubMed  Google Scholar 

  19. Rich TA, Skibber JM, Ajani JA,et al. Preoperative infusional chemoradiation therapy for stage T3 rectal cancer. Int J Radiat Oncol Biol Phys 1995;32:1025–9.

    Article  PubMed  Google Scholar 

  20. Swedish Rectal Cancer Trial. Initial report from a Swedish multicentre study examining the role of preoperative irradiation in the treatment of patients with resectable rectal carcinoma. Br J Surg 1993;80:1333–6.

    Google Scholar 

  21. Ooi BS, Tjandra JJ, Green MD. Morbidities of adjuvant chemotherapy and radiotherapy for resectable rectal cancer: an overview. Dis Colon Rectum 1999;42:403–18.

    Google Scholar 

  22. Perez CA, Brady LW. Overview of radiation oncology. In: Perez CA, Brady LW, eds. Principles and practice of radiation oncology. 2nd ed. Philadelphia: Lippincott, 1992;51–5.

    Google Scholar 

  23. Berger C, de Muret A, Garaud P,et al. Preoperative radiotherapy (RT) for rectal cancer: predictive factors of tumor downstaging and residual tumor cell density (RTCD): prognostic implications. Int J Radiat Oncol Biol Phys 1997;37:619–27.

    Article  PubMed  Google Scholar 

  24. Myerson RJ, Michalski JM, King ML,et al. Adjuvant radiation therapy for rectal carcinoma: predictors of outcome. Int J Radiat Oncol Biol Phys 1995;32:41–50.

    Article  PubMed  Google Scholar 

  25. Valentini V, Coco C, Cellini N,et al. Preoperative chemoradiation for extraperitoneal T3 rectal cancer: acute toxicity, tumor response, and sphincter preservation. Int J Radiat Oncol Biol Phys 1998;40:1067–75.

    Article  PubMed  Google Scholar 

  26. Marsh RD, Chu NM, Vauthey JN,et al. Preoperative treatment of patients with locally advanced unresectable rectal adenocarcinoma utilizing continuous chronobiologically shaped 5-fluorouracil infusion and radiation therapy. Cancer 1996;78:217–25.

    Article  PubMed  Google Scholar 

  27. Habr-Gama A, de Souza PM, Ribeiro U Jr,et al. Low rectal cancer: impact of radiation and chemotherapy on surgical treatment. Dis Colon Rectum 1998;41:1087–96.

    PubMed  Google Scholar 

  28. Videtic GM, Fisher BJ, Perera FE,et al. Preoperative radiation with concurrent 5-fluorouracil continuous infusion for locally advanced unresectable rectal cancer. Int J Radiat Oncol Biol Phys 1998;42:319–24.

    Article  PubMed  Google Scholar 

  29. Chen ET, Mohiuddin M, Brodovsky H, Fishbein G, Marks G. Downstaging of advanced rectal cancer following combined preoperative chemotherapy and high dose radiation. Int J Radiat Oncol Biol Phys 1994;30:169–75.

    PubMed  Google Scholar 

  30. Bosset JF, Pavy JJ, Hamers HP,et al. Determination of the optimal dose of 5-fluorouracil when combined with low doseD,L-leucovorin and irradiation in rectal cancer: results of three consecutive phase II studies. EORTC Radiotherapy Group. Eur J Cancer 1993;29A:1406–10.

    Article  PubMed  Google Scholar 

  31. Minsky BD, Cohen AM, Enker WE,et al. Preoperative 5-FU, low-dose leucovorin, and radiation therapy for locally advanced and unresectable rectal cancer. Int J Radiat Oncol Biol Phys 1997;37:289–95.

    Article  PubMed  Google Scholar 

  32. 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.

    Article  PubMed  Google Scholar 

  33. Meterissian S, Skibber J, Rich T,et al. Patterns of residual disease after preoperative chemoradiation in ultrasound T3 rectal carcinoma. Ann Surg Oncol 1994;1:111–6.

    PubMed  Google Scholar 

  34. Janjan NA, Khoo VS, Abbruzzese J,et al. Tumor down-staging and sphincter preservation with preoperative chemoradiation in locally advanced rectal cancer: the M. D. Anderson Cancer Center experience. Int J Radiat Oncol Biol Phys 1999;44:1027–38.

    Article  PubMed  Google Scholar 

  35. Chan A, Wong A, Langevin J, Khoo R. Preoperative concurrent 5-fluorouracil infusion, mitomycin C and pelvic radiation therapy in tethered and fixed rectal carcinoma. Int J Radiat Oncol Biol Phys 1993;25:791–9.

    PubMed  Google Scholar 

  36. Kaminsky-Forrett MC, Conroy T, Luporsi E,et al. Prognostic implications of downstaging following preoperative radiation therapy for operable T3–T4 rectal cancer. Int J Radiat Oncol Biol Phys 1998;42:935–41.

    Article  PubMed  Google Scholar 

  37. Myerson RJ, Genovesi D, Lockett MA,et al. Five fractions of preoperative radiotherapy for selected cases of rectal carcinoma: long-term tumor control and tolerance to treatment. Int J Radiat Oncol Biol Phys 1999;43:537–43.

    Article  PubMed  Google Scholar 

  38. Kodner IJ, Shemesh EI, Fry RD,et al. Preoperative irradiation for rectal cancer. Improved local control and long-term survival. Ann Surg 1989;209:194–9.

    PubMed  Google Scholar 

  39. Fleshman JW, Myerson RJ, Fry RD, Kodner IJ. Accuracy of transrectal ultrasound in predicting pathologic stage of rectal cancer before and after preoperative radiation therapy. Dis Colon Rectum 1992;35:823–9.

    PubMed  Google Scholar 

  40. Ch'ang HJ, Jian JJ, Cheng SH,et al. Preoperative concurrent chemotherapy and radiotherapy in rectal cancer patients. J Formos Med Assoc 1998;97:32–7.

    PubMed  Google Scholar 

  41. Janjan NA, Khoo VS, Rich TA,et al. Locally advanced rectal cancer: surgical complications after infusional chemotherapy and radiation therapy. Radiology 1998;206:131–6.

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  43. Zaheer S, Pemberton JH, Farouk R, Dozois RR, Wolff BG, Ilstrup D. Surgical treatment of adenocarcinoma of the rectum. Ann Surg 1998;227:800–11.

    Article  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  45. 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.

    Article  PubMed  Google Scholar 

  46. 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.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Heather Whiteford, M.D. was supported by the Wallace R. Ruwitch Family Research Fund.

The colorectal cancer database is supported in part by the St. Louis Men's Group Against Cancer.

About this article

Cite this article

Read, T.E., McNevin, M.S., Gross, E.K.M. et al. Neoadjuvant therapy for adenocarcinoma of the rectum: Tumor response and acute toxicity. Dis Colon Rectum 44, 513–522 (2001). https://doi.org/10.1007/BF02234323

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02234323

Key words

Navigation