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Information Libraries: Colon Cancer

This information is produced and provided by the National Cancer Institute (NCI).


Table Of Contents

GENERAL INFORMATION

Cancer of the colon is a highly treatable and often curable disease when localized to the bowel. It is the second most frequently diagnosed malignancy in the United States as well as the second most common cause of cancer death.

Surgery is the primary treatment and results in cure in approximately 50% of patients. Recurrence following surgery is a major problem and often is the ultimate cause of death. The prognosis of colon cancer is clearly related to the degree of penetration of the tumor through the bowel wall and the presence or absence of nodal involvement. These two characteristics form the basis for all staging systems developed for this disease. Bowel obstruction, bowel perforation, and adhesion to or invasion of adjacent structures are indicators of poor prognosis.[1] Elevated pretreatment serum levels of carcinoembryonic antigen (CEA) and of carbohydrate antigen 19-9 (CA 19-9) have a negative prognostic significance.[2] Age greater than 70 years at presentation is not a contraindication to standard therapies; acceptable morbidity and mortality, as well as long-term survival, are achieved in this patient population.[3]

Because of the frequency of the disease (approximately 160,000 new cases of colon and rectal cancer per year), the identification of high-risk groups, the demonstrated slow growth of primary lesions, the better survival of early-stage lesions, and the relative simplicity and accuracy of screening tests, screening for colon cancer should be a part of routine care for all adults starting at age 50, especially those with first-degree relatives with colorectal cancer.[4]

Careful screening of high-risk populations (patients with panulcerative colitis, previous colon cancer, a family history of colon or female genital cancer, or a history of sporadic colon polyps) should include periodic stool occult blood evaluation and appropriate radiologic and endoscopic studies. Specific genetic alterations have been recognized in the two major conditions predisposing familial colorectal cancer, familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer.[5,6] As practical assays are developed and validated, such detectable genetic abnormalities may be used in the future to screen members of high-risk families, particularly those with familial adenomatous polyposis.[7] For more information on this subject, consult the PDQ statements on screening and prevention of colorectal cancer.

Following treatment for colon cancer, periodic determinations of serum CEA levels, radiographic and laboratory studies, and physical examination may lead to the earlier identification and management of recurrent disease.[8] The impact of such monitoring on overall mortality of patients with recurrent colon cancer is limited by the relatively small proportion of patients in whom localized, potentially curable metastases are found. To date, there have been no large-scale randomized trials documenting the efficacy of a standard postoperative monitoring program.[9,10] Postoperative monitoring should be reserved primarily for detection of asymptomatic recurrences that can be curatively resected and for early detection of metachronous tumors.[11,12]

Adjuvant therapy

Many early trials of adjuvant chemotherapy failed to show a significant improvement in either overall or disease-free survival for patients receiving treatment compared to concurrently randomized control patients receiving no adjuvant therapy.[13-16]

A subsequent generation of large prospective randomized trials, however, has demonstrated consistent evidence of benefit for systemic adjuvant chemotherapy employing fluorouracil plus either levamisole or leucovorin. The first positive trial employed a regimen that is no longer used. In 1988, the National Surgical Adjuvant Breast and Bowel Project (NSABP) demonstrated improved disease-free survival and an overall survival benefit of 8% at 5 years of follow-up for patients with stages II and III (Dukes' B and C and Modified Astler-Coller (MAC) B2, B3, and C1-C3) treated with postoperative MOF chemotherapy consisting of fluorouracil (5-FU), semustine (methyl-CCNU), and vincristine.[17] However, after 8 years of follow-up, this benefit was no longer apparent. In 1990, a large intergroup trial of 5-FU/levamisole reported prolonged disease-free and overall survival in patients with stage III colon cancer, compared to patients who received no treatment after surgery.[18] This benefit has persisted with continued follow-up.[19] Levamisole alone did not confer these benefits, and it was not clear whether 5-FU/levamisole was effective in stage II patients.

The NSABP then reported a trial for stage II and III patients comparing the original MOF regimen to a weekly regimen of 5-FU plus high-dose leucovorin. This demonstrated a statistically significant benefit for 5-FU/leucovorin in both overall and disease-free survival.[20] Adjuvant 5-FU plus leucovorin (in different treatment schedules) was also compared to surgery alone in 4 large randomized trials that closed prematurely in the early 1990s when surgery alone control arms were no longer felt to represent standard care for stage III patients. Three of these trials, conducted in Canada, France, and Italy, have had their primary data pooled and analyzed together. The 3-year event-free and overall survival rates were also statistically significantly improved in this analysis.[21,22] Taken together, about 4,000 patients have participated in the positive randomized trials comparing adjuvant chemotherapy to surgery alone with a reduction in mortality of between 22% and 33%. These results are quite clear in stage III patients but uncertain in stage II patients. Adjuvant treatment for stage III colon cancer appears to be cost-effective when costs of treatment and quality-of-life measures are taken into account.[23]

At this time, patients with stage III (Dukes' C) colon cancer should be considered for adjuvant therapy with 5-FU/levamisole, with 5-FU/leucovorin, or with one of the other regimens now being studied in clinical trials.[24] Regional adjuvant therapy directed at reducing liver metastasis has been tested using both portal vein infusion of 5-FU and hepatic radiation, and an early trial by Taylor showed promising results.[25] The preliminary results of confirmatory trials from the NSABP, the Mayo Clinic, and the United Kingdom Large Bowel Cancer Project, however, have failed to demonstrate a significant benefit for hepatic-directed adjuvant therapy in the reduction of liver recurrences.[26-28] The NSABP trial, but not the Mayo Clinic trial, showed a modest benefit in survival but no change in the incidence of liver metastases. Neither prolongation of survival nor reduction of liver recurrences was seen in a Gastrointestinal Tumor Study Group study of adjuvant hepatic radiation with 5-FU.[29]

Advanced disease

For locally advanced disease, the role of radiation therapy in colon cancer is under clinical evaluation. There is no standard therapy for advanced colon cancer and no evidence that chemotherapy improves survival, although short-term palliation may be achieved in approximately 10%-20% of patients with 5-FU. Several studies suggest an advantage when leucovorin or methotrexate is added to 5-FU in terms of response rate and palliation of symptoms, but not always in terms of survival.[30-34]

Some retrospective studies suggest that perioperative blood transfusions impair prognosis of patients with colorectal cancer.[35,36] A small, single-institution, prospective randomized trial found the need for allogeneic transfusions following resection of colorectal cancer was an independent predictor of tumor recurrence.[37] This finding was not confirmed by a large, multi-institutional, prospective randomized trial which demonstrated no benefit for autologous blood transfusions when compared to allogeneic transfusions.[38] Both studies established that patients who do not require any blood transfusion have a reduced risk of recurrence, but it would be premature to change transfusion procedures based on these results as other studies have not confirmed this finding.[39]

References:

  1. Steinberg SM, Barkin JS, Kaplan RS, et al.: Prognostic indicators of colon tumors: the Gastrointestinal Tumor Study Group experience. Cancer 57(9): 1866-1870, 1986.
  2. Filella X, Molina R, Grau JJ, et al.: Prognostic value of CA 19.9 levels in colorectal cancer. Annals of Surgery 216(1): 55-59, 1992.
  3. Fitzgerald SD, Longo WE, Daniel GL, et al.: Advanced colorectal neoplasia in the high-risk elderly patient: is surgical resection justified? Diseases of the Colon and Rectum 36(2): 161-166, 1993.
  4. Cannon-Albright LA, Skolnick MH, Bishop DT, et al.: Common inheritance of susceptibility to colonic adenomatous polyps and associated colorectal cancers. New England Journal of Medicine 319(9): 533-537, 1988.
  5. Peltomaki P, Aaltonen LA, Sistonen P, et al.: Genetic mapping of a locus predisposing to human colorectal cancer. Science 260(5109): 810-812, 1993.
  6. Aaltonen LA, Peltomaki P, Leach FS, et al.: Clues to the pathogenesis of familial colorectal cancer. Science 260(5109): 812-816, 1993.
  7. Powell SM, Petersen GM, Krush AJ, et al.: Molecular diagnosis of familial adenomatous polyposis. New England Journal of Medicine 329(27): 1982-1987, 1993.
  8. Martin EW, Minton JP, Carey LC: CEA-directed second-look surgery in the asymptomatic patient after primary resection of colorectal carcinoma. Annals of Surgery 202(1): 310-317, 1985.
  9. Safi F, Link KH, Beger HG: Is follow-up of colorectal cancer patients worthwhile? Diseases of the Colon and Rectum 36(7): 636-644, 1993.
  10. Moertel CG, Fleming TR, Macdonald JS, et al.: An evaluation of the carcinoembryonic antigen (CEA) test for monitoring patients with resected colon cancer. Journal of the American Medical Association 270(8): 943-947, 1993.
  11. Bruinvels DJ, Stiggelbout AM, Kievit J, et al.: Follow-up of patients with colorectal cancer: a meta-analysis. Annals of Surgery 219(2): 174-182, 1994.
  12. Lautenbach E, Forde KA, Neugut AI: Benefits of colonoscopic surveillance after curative resection of colorectal cancer. Annals of Surgery 220(2): 206-211, 1994.
  13. Panettiere FJ, Goodman PJ, Costanzi JJ, et al.: Adjuvant therapy in large bowel adenocarcinoma: long-term results of a Southwest Oncology Group study. Journal of Clinical Oncology 6(6): 947-954, 1988.
  14. Gastrointestinal Tumor Study Group: Adjuvant therapy of colon cancer: results of a prospectively randomized trial. New England Journal of Medicine 310(12): 737-743, 1984.
  15. Higgins GA, Amadeo JH, McElhinney J, et al.: Efficacy of prolonged intermittent therapy with combined 5-fluorouracil and methyl-CCNU following resection for carcinoma of the large bowel: a Veterans Administration Surgical Oncology Group report. Cancer 53(1): 1-8, 1984.
  16. Buyse M, Zeleniuch-Jacquotte A, Chalmers TC: Adjuvant therapy of colorectal cancer: why we still don't know. Journal of the American Medical Association 259(24): 3571-3578, 1988.
  17. Wolmark N, Fisher B, Rockette H, et al.: Postoperative adjuvant chemotherapy or BCG for colon cancer: results from NSABP protocol C-01 [Prior Annotation Incorrect]. Journal of the National Cancer Institute 80(1): 30-36, 1988.
  18. Moertel CG, Fleming TR, Macdonald JS, et al.: Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. New England Journal of Medicine 322(6): 352-358, 1990.
  19. Moertel CG, Fleming TR, Macdonald JS, et al.: Fluorouracil plus levamisole as effective adjuvant therapy after resection of stage III colon carcinoma: a final report. Annals of Internal Medicine 122(5): 321-326, 1995.
  20. Wolmark N, Rockette H, Fisher B, et al.: The benefit of leucovorin-modulated fluorouracil as postoperative adjuvant therapy for primary colon cancer: results from National Surgical Adjuvant Breast and Bowel Project protocol C-03 [Prior Annotation Incorrect]. Journal of Clinical Oncology 11(10): 1879-1887, 1993.
  21. International Multicentre Pooled Analysis of Colon Cancer Trials: Efficacy of adjuvant fluorouracil and folinic acid in colon cancer. Lancet 345(8955): 939-944, 1995.
  22. O'Connell M, Mailliard J, Macdonald J, et al.: An intergroup trial of intensive course 5FU and low dose leucovorin as surgical adjuvant therapy for high risk colon cancer. Proceedings of the American Society of Clinical Oncology 12: A-552, 190, 1993.
  23. Brown ML, Nayfield SG, Shibley LM: Adjuvant therapy for stage III colon cancer: economics returns to research and cost-effectiveness of treatment. Journal of the National Cancer Institute 86(6): 424-430, 1994.
  24. National Institutes of Health: NIH Consensus Conference: adjuvant therapy for patients with colon and rectal cancer. Journal of the American Medical Association 264(11): 1444-1450, 1990.
  25. Taylor I, Machin D, Mullee M, et al.: A randomized controlled trial of adjuvant portal vein cytotoxic perfusion in colorectal cancer. British Journal of Surgery 72(5): 359-363, 1985.
  26. Wolmark N, Rockette H, Wickerham DL, et al.: Adjuvant therapy of Dukes' A, B, and C adenocarcinoma of the colon with portal-vein fluorouracil

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