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Locally advanced rectal cancer (LARC) carries higher risks of local and distant recurrence when treated with surgical resection alone. Multiple treatment strategies have been investigated to reduce recurrence risk and improve survival. Currently, there are 3 primary strategies for managing LARC: (1) preoperative long-course radiotherapy (RT) combined with radiosensitizing chemotherapy, which is better tolerated than postoperative chemoradiotherapy and provides tumor downstaging and improved pathologic complete response (pCR), followed by postoperative chemotherapy; (2) preoperative short-course RT alone as an alternative strategy for reducing the risk of local recurrence, followed by adjuvant postoperative chemotherapy; and (3) total neoadjuvant therapy with induction chemotherapy followed by chemoradiotherapy to improve pCR and reduce the difficulty of delivering chemotherapy in the postoperative setting. In addition to these currently recommended treatment paradigms, promising new strategies are available for treatment reduction. Neoadjuvant chemotherapy alone may allow for omission of RT in select patients with favorable LARC. For patients who have complete clinical responses to neoadjuvant chemotherapy and RT, nonoperative management is being considered for sphincter preservation, with surgery used as salvage. These are active areas of investigation in both institutional and cooperative group trials. The results are anticipated to provide better tailoring of neoadjuvant therapy based on patient tumor and disease response characteristics.

Definitive chemoradiotherapy (CRT) for anal cancer spares patients the morbidity of a colostomy surgery and optimizes cancer outcomes. CRT, however, has introduced a unique acute and chronic toxicity profile, which has greatly improved over the years with the introduction of advanced radiotherapy techniques. This article provides the multidisciplinary care team with practical tools to mitigate and manage acute and chronic complications from definitive treatment of anal cancer.