General Medical Information

Colon Cancer

April 11, 2007 on 9:12 pm | In Cancer |

Cancer of the colon is a highly treatable and often curable disease when localized to the bowel. Surgery is the primary form of 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 2 characteristics form the basis for all staging systems developed for this disease. Bowel obstruction and bowel perforation are indicators of poor prognosis.[1] Elevated pretreatment serum levels of carcinoembryonic antigen (CEA) have a negative prognostic significance.[2] Many other prognostic markers have been evaluated retrospectively in the prognosis of patients with colon cancer, although most, including allelic loss of chromosome 18q or thymidylate synthase expression, have not been prospectively validated.[3-5] Microsatellite instability, also associated with hereditary nonpolyposis colon cancer, has been shown to be associated with improved survival independent of tumor stage in a population-based series of 607 patients less than 50 years of age with colorectal cancer.[6] Age greater than 65 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.[7-9] Racial differences in overall survival after adjuvant therapy have been observed, without differences in disease-free survival, suggesting that comorbid conditions play a role in survival outcome in different patient populations.[10]

Because of the frequency of the disease, the identification of high-risk groups, the demonstrated slow growth of primary lesions, the better survival of patients with 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 years, especially for those with first-degree relatives with colorectal cancer. There are groups that have a high incidence of colorectal cancer. These groups include those with hereditary conditions, such as familial polyposis, hereditary nonpolyposis colon cancer (HNPCC) or Lynch SyndromeVariants I and II, and ulcerative colitis.[11] Together they account for 10% to 15% of colorectal cancers. Patients with HNPCC reportedly have better prognoses in stage-stratified survival analysis than patients with sporadic colorectal cancer, but the retrospective nature of the studies and possibility of selection factors make this observation difficult to interpret.[12][Level of evidence: 3iiiA] More common conditions with an increased risk include: a personal history of colorectal cancer or adenomas, first degree family history of colorectal cancer or adenomas, and a personal history of ovarian, endometrial, or breast cancer.[13,14] These high-risk groups account for only 23% of all colorectal cancers. Limiting screening or early cancer detection to only these high-risk groups would miss the majority of colorectal cancers.[15] (Refer to the PDQ summaries on Screening for Colorectal Cancer and Prevention of Colorectal Cancer for more information.)

Following treatment of colon cancer, periodic evaluations may lead to the earlier identification and management of recurrent disease.[16-19] However, 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.[20-24] CEA is a serum glycoprotein frequently used in the management of patients with colon cancer. A review of the use of this tumor marker suggests: that CEA is not a valuable screening test for colorectal cancer due to the large numbers of false-positive and false-negative reports; that postoperative CEA testing be restricted to patients who would be candidates for resection of liver or lung metastases; and that routine use of CEA alone for monitoring response to treatment not be recommended.[25] However, the optimal regimen and frequency of follow-up examinations are not well defined, since the impact on patient survival is not clear and the quality of data is poor.[22-24] New surveillance methods including CEA immunoscintigraphy [26] and positron emission tomography are under clinical evaluation.
Gastrointestinal stromal tumors can occur in the colon. (Refer to the PDQ summary on Adult Soft Tissue Sarcoma Treatment for more information.)

Adjuvant therapy
The current generation of large prospective randomized trials has demonstrated consistent evidence of benefit for systemic adjuvant chemotherapy employing fluorouracil (5-FU) plus either levamisole or leucovorin. 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.[27] This benefit has persisted with continued follow-up.[28]

The National Surgical Adjuvant Breast and Bowel Project (NSABP) then reported a trial for stage II and III patients comparing the fluorouracil/semustine/ vincristine 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.[29] 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 recurrence-free and overall survival rates were also statistically significantly improved in this analysis.[30,31] 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 of stage III colon cancer appears to be cost-effective when costs of treatment and quality-of-life measures are taken into account.[32] At this time, patients with stage III (Dukes’ C) colon cancer should be considered for adjuvant therapy with 5-FU/leucovorin for 6 to 8 months.[33,34]

Advanced disease
For locally advanced disease, the role of radiation therapy with chemotherapy in colon cancer is under clinical evaluation. Palliation may be achieved in approximately 10% to 20% of patients with 5-FU. Several studies suggest an advantage when leucovorin is added to 5-FU in terms of response rate and palliation of symptoms, but not always in terms of survival.[35-41] Irinotecan (CPT-11) has been approved by the Food and Drug Administration for the treatment of patients whose tumors are refractory to 5-FU.[42-45] Participation in clinical trials is appropriate. A number of other drugs are undergoing evaluation for the treatment of colon cancer.[46] Oxaliplatin, alone or combined with 5-FU and leucovorin, has also shown activity in 5-FU refractory patients.[47-50]

Some retrospective studies suggest that perioperative blood transfusions impair prognosis of patients with colorectal cancer.[51,52] 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.[53] 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.[54] 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.[55] There are a large number of studies correlating various clinical, pathological, and molecular parameters with prognosis, but none of these parameters has been demonstrated to be as important as pathologic stage, and none yet has a major impact on choice of, or outcome from, therapy.[3,4,56-62]

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