The Neoadjuvant Treatment of Rectal Cancer: A Review

Rectal adenocarcinoma is an important cause of cancer-related deaths worldwide, and key anatomic differences between the rectum and the colon have significant implications for management of rectal cancer, especially in the curative setting. For stage II and III rectal cancers, combined chemoradiotherapy offers the lowest rates of local and distant relapse, and is delivered neoadjuvantly to improve tolerability and optimize surgical outcomes, particularly when sphincter-sparing surgery is an endpoint. We review both pivotal trial data that has shaped the current standard of care, fluoropyrimidine-based chemoradiotherapy, while also presenting results from more recent studies, which aim to outperform this standard. Strategies combining 5FU radiotherapy with oxaliplatin, VEGF inhibition, EGFR inhibition, other targeted agents, and/or use of induction chemotherapy hold promise but thus far have failed to improve outcomes in randomized trials. Results of studies such as the ongoing PROSPECT trial may help further define our current therapeutic algorithm for stage II and III rectal cancer.