Should Upfront Chemotherapy Precede Preoperative Chemoradiation and Surgery?
Distant relapse has become the biggest problem in locally advanced cancer of the rectum and is the most frequent reason for the mortality of these patients. As compared with radiation alone, preoperative combined modality treatment with 5FU and radiation increase the pathological complete response (pCR) rate over radiotherapy alone, and improve locoregional control but to date have not demonstrated an improvement in disease-free survival (DFS) or overall survival (OS). Applying chemotherapy after preoperative chemoradiation (CRT) and surgery is problematic and often not feasible, as has been shown in several phase III and phase II trials. One strategy to address this issue is to deliver upfront chemotherapy prior to preoperative CRT. Compared with postoperative chemotherapy, the upfront strategy did not appear to improve pCR; it did achieve a better toxicity profile, improved compliance with treatment and greater exposure to systemic treatment. This can be important for patients at higher risk of distant relapse. Introducing systemic active combination chemotherapy prior to chemoradiation and surgery with an adequate selection of the high-risk population may well be the next step in phase III testing in order to improve DFS.
KeywordsOverall Survival Rectal Cancer Adjuvant Chemotherapy National Comprehensive Cancer Network Pathological Complete Response
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