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Rectal and colon adenocarcinoma originate from the same epithelial cell types and share the same histologic features. Unlike the colon, the rectum lacks a peritoneal lining, and the tight confines of the pelvis pose a challenge to surgical resection with clear margins. These features may explain the higher local recurrence rates seen in rectal cancer compared with colon cancer. Prior to the advent of multimodality treatment of rectal cancer, local recurrence rates of 5% to 10% for stage I, 25% to 30% for stage II, and >50% for stage III tumors were reported.1 Pelvic radiation therapy offers a protective effect against local recurrence, and over the past decades preoperative (neoadjuvant) timing has prevailed. The effects of radiation on tumor eradication can be potentiated with concurrent chemotherapy, particularly with fluorouracil-based chemotherapy. However, surgical management with a total mesorectal excision (TME) remains as the key feature of modern rectal cancer care.

Preoperative radiation allows for tumor oxygenation through the intact blood supply. Preoperative treatment is better tolerated than postoperative treatment, as demonstrated in the German Rectal Cancer Study Group study in which 89% of patients randomized to preoperative chemoradiation completed treatment, but among patients randomized to postoperative treatment only 50% of patients received a full dose of chemotherapy and only 54% received full-dose radiotherapy. The relatively high complication rate after rectal cancer surgery is likely to explain this gap in compliance. The advantage of postoperative chemoradiation is that a true tumor stage is available from the surgical specimen, so the indication for this treatment is more accurately determined. Surgical resection may be less challenging in a pelvis that has not been preoperatively radiated, though this has been hard to prove. Some studies have shown that perineal wound healing in abdominoperineal resection (APR) patients is more challenging after any radiation treatment. A major criticism of our reliance on radiation is the long-term side effects of pelvic radiation, which are well documented. As it is not clear that pelvic radiation achieves a survival benefit, a legitimate argument can be made to more closely examine the long-term quality of life implications of pelvic radiation. Furthermore, a more finely tuned selective approach to using radiation has been hampered by our inability to accurately clinically stage patients upon diagnosis. While much progress has been made in this regard, particularly with advances in MRI technology, results of such research is frequently confounded by the fact that neoadjuvant radiation or chemoradiation is commonly administered and frequently downstages the primary tumor, eliminating the gold standard of histopathology of the primary tumor.

In this chapter, the various approaches to neoadjuvant and adjuvant multimodality treatment of rectal cancer are summarized, with an attention to data from randomized controlled trials. Outcomes of local recurrence, primary tumor response to neoadjuvant treatment, overall survival, disease-free survival, surgical complications, and bowel, bladder, and sexual functions are examined. This chapter focuses on curative radical surgery for rectal cancer and does not ...

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