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Determination of the stage of colorectal cancer is important not only because it correlates with the patient s long-term survival but also because it is used to determine which patients should receive adjuvant therapy (see Additional Reading at the end of the chapter) Although the Dukes classification has been widely used in the past, the TNM system is now more commonly used
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Resection of the primary colonic or rectal cancer is the treatment of choice for almost all patients who have resectable lesions and can tolerate general anesthesia Multiple studies demonstrate that minimally invasive, laparoscopically assisted colectomy results in similar outcomes and rates of recurrence to open colectomy Regional lymph node dissection should be performed to determine staging, which guides decisions about adjuvant therapy Even patients with extensive metastatic disease may benefit from resection of the colonic tumor to reduce the likelihood of intestinal obstruction or serious bleeding For rectal carcinoma, the operative approach depends on the level of the tumor above the anal verge, the size and depth of penetration, and the patient s overall condition Clinical staging by endorectal ultrasound or MRI with endorectal coil is important in guiding the clinical approach In carefully selected patients with small, mobile (< 4 cm), well-differentiated T1 or T2 rectal tumors that are less than 8 cm from the anal verge and that appear on endosonography to be localized to the rectal wall, transanal excision may be performed This approach avoids laparotomy and spares the rectum and anal
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rectal cancers It has long been controversial whether chemoradiation should be administered preoperatively ( neoadjuvant ) or postoperatively ( adjuvant ) Neoadjuvant therapy may decrease the size of the tumor before surgery (tumor downstaging), allowing more patients to undergo curative resection with sphincter preservation rather than abdominoperineal resection When initial imaging studies suggest stage I disease, surgery may be performed first, followed by postoperative chemoradiation in patients found at surgery to have more advanced (stage II or III) disease A recent, large, randomized controlled trial reported that preoperative therapy led to better patient treatment compliance, reduced local recurrence and toxicity, and a higher number of sphincterpreserving resections Therefore, preoperative chemoradiation increasingly is recommended for patients with distal rectal cancers that are determined to be stage II or III by endorectal ultrasound or MRI
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patients with Stage III disease Current studies are evaluating oral capecitabine in combination with oxaliplatin The role of combination adjuvant therapy of FOLFOX plus a biologic agent (bevacixumab, cetuximab, or panituxumab) also is under investigation 4 Stage IV (metastatic disease) Approximately 20% of patients have metastatic disease at the time of initial diagnosis, and another 30% eventually develop metastasis The long-term survival of these patients is only 5%, and the median survival is only 6 months in the absence of other treatment Resection of isolated (one to three) liver or lung metastases may result in long-term (over 5 years) survival in 35 55% of cases For those with unresectable hepatic metastases, local ablative techniques (cryosurgery, radiofrequency or microwave coagulation, embolization, hepatic intra-arterial chemotherapy) may provide long-term tumor control Approximately 20% of patients with metastatic disease respond to chemotherapy regimens containing intravenous 5-FU and folinic acid (leucovorin) or the oral 6-FU analog capecitabine, prolonging median survival to about 11 months However, the addition of either oxaliplatin (FOLFOX) or irinotecan (FOLFIRI; IFL) to 5-FU and folinic acid provides further improvement in tumor response rate (40%) and median survival (15 20 months) Currently, FOLFOX and FOLFIRI are the preferred first-line treatment regimens for most patients with metastatic colorectal cancer Patients progressing with one regimen may respond to the alternative regimen, prolonging mean survival to > 20 months The role of oral capecitabine (instead of intravenous 5-FU) in combination with oxaliplatin or irinotecan is under investigation The most recent advance in the treatment of metastatic colon cancer is the development of the biologic agents, cetuximab, panitumumab, and bevacizumab The role of these agents is rapidly evolving Cetuximab and panitumumab are monoclonal antibodies to EGFR; bevacizumab is a monoclonal antibody to vascular endothelial growth factor (VEGF) Combination therapy with bevacizumab and FOLFOX or FOLFIRI prolong mean survival 2 5 months compared with either regimen alone Therefore, many oncologists are now using one of these combinations for initial therapy of metastatic disease Bevacizumab may cause serious thromboembolic events (including stroke and myocardial infarction) in 5% of patients Cetuximab and panitumumab have modest efficacy when used as single agents for second-line therapy in patients whose disease has progressed on chemotherapeutic regiments containing 5-FU, irinotecan, or oxaliplatin The role of these agents in combination with FOLFOX and FOLFIRI is under investigation Similarly, the role of combination therapy of bevacizumab plus cetuximab or panitumumab with or without other agents requires further study
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