Adjuvant therapy
Advanced disease

Note: Separate PDQ summaries on Screening for Colorectal Cancer and Prevention of Colorectal Cancer are also available.

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Cancer of the rectum is a highly treatable and often curable disease when localized. Surgery is the primary treatment and results in cure in approximately 45% of all patients. The prognosis of rectal 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. Preoperative staging procedures include digital rectal examination, computed tomographic scan or magnetic resonance imaging scan of the abdomen and pelvis, endoscopic evaluation with biopsy, and endoscopic ultrasound (EUS).[1] EUS is an accurate method of evaluating tumor stage (up to 95% accuracy) and the status of the perirectal nodes (up to 74% accuracy). Accurate staging can influence therapy by helping to determine which patients may be candidates for local excision rather than more extensive surgery and which patients may be candidates for preoperative chemotherapy and radiation therapy to maximize the likelihood of resection with clear margins. Many other prognostic markers have been evaluated retrospectively in the prognosis of patients with rectal cancer, although most, including allelic loss of chromosome 18q or thymidylate synthase expression, have not been prospectively validated.[2-4] Microsatellite instability, also associated with hereditary nonpolyposis rectal 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.[5] 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.[6] A major limitation of surgery is the inability to obtain wide radial margins because of the presence of the bony pelvis. In those patients with disease penetration through the bowel wall and/or spread into lymph nodes at the time of diagnosis, local recurrence following surgery is a major problem and often ultimately results in death.[7] The radial margin of resection of rectal primaries may also predict for local recurrence.[8]

Because of the frequency of the disease, 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 rectal cancer should be a part of routine care for all adults over the age of 50 years, especially those with first-degree relatives with colorectal cancer.[9] 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 Syndrome Variants I and II, and ulcerative colitis.[10] (Refer to the PDQ summary on Genetics of Colorectal Cancer for more information.) 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 the possibility of selection factors make this observation difficult to interpret.[11] [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.[12,13] 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.[14] (Refer to the PDQ summaries on Screening for Colorectal Cancer and Prevention of Colorectal Cancer for more information.)

Following treatment of rectal cancer, periodic evaluations may lead to the earlier identification and management of recurrent disease.[15-18] However, the impact of such monitoring on overall mortality of patients with recurrent rectal 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.[19-23] Carcinoembryonic antigen (CEA) is a serum glycoprotein frequently used in the management of patients with rectal cancer. A review of the use of this tumor marker suggests: that CEA is not useful as a screening test; 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.[24] 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.[21-23] New surveillance methods including CEA immunoscintigraphy and positron tomography are under clinical evaluation.[25]

Although a large number of studies have evaluated various clinical, pathological, and molecular parameters with prognosis, as yet, none have had a major impact on prognosis or therapy.[26] Clinical stage remains the most important prognostic indicator.

Gastrointestinal stromal tumors can occur in the rectum. (Refer to the PDQ summary on Adult Soft Tissue Sarcoma Treatment for more information.)

Patients with stage II or III rectal cancer are at high risk for local and systemic relapse. Adjuvant therapy should address both problems. Most trials of preoperative or postoperative radiation therapy alone have shown a decrease in the local recurrence rate but no definite effect on survival;[15,27-30] although a Swedish trial has shown a survival advantage from preoperative radiation therapy compared to surgery alone.[31] [Level of evidence: 1iiA] Two trials have confirmed that fluorouracil (5-FU) plus radiation therapy is effective and may be considered standard treatment.[27-29] In these trials, combined modality adjuvant treatment with radiation therapy and chemotherapy following surgery also resulted in local failure rates lower than with either radiation therapy or chemotherapy alone. An analysis of patients treated with postoperative chemotherapy and radiation therapy suggests that these patients may have more chronic bowel dysfunction compared to those who undergo surgical resection alone.[32] Improved radiation planning and techniques can be used to minimize treatment-related complications. These techniques include the use of multiple pelvic fields, prone positioning, customized bowel immobilization molds (belly boards), bladder distention, visualization of the small bowel with oral contrast, and the incorporation of three-dimensional or comparative treatment planning.[33,34] Ongoing clinical trials comparing preoperative and postoperative adjuvant chemoradiotherapy should further clarify the impact of either approach on bowel function and other important quality-of-life issues (e.g., sphincter preservation) in addition to the more conventional endpoints of disease-free and overall survival.

Radiation therapy in rectal cancer is palliative in most situations but may have greater impact when used perioperatively. 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]

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