Future directions in combined modality therapy for rectal cancer: reevaluating the role of total mesorectal excision after chemoradiotherapy

Most patients who develop rectal cancer present with locoregionally advanced (T3 or node-positive) disease. The standard management of locoregionally advanced rectal cancer is neoadjuvant concurrent chemoradiotherapy (nCRT), followed by radical resection (low-anterior resection or abdominoperineal resection with total mesorectal excision). Approximately 15% of patients can have a pathologic complete response (pCR) at the time of surgery, indicating that some patients can have no detectable residual disease after nCRT. The actual benefit of surgery in this group of patients is unclear. It is possible that omission of surgery in these patients, termed selective nonoperative management, can limit the toxicities associated with standard, multimodal combined modality therapy without compromising disease control. In this review, we discuss the clinical experiences to date using selective nonoperative management and various attempts at escalation of nCRT to improve the number of patients who have a pCR. We also explore several clinical, laboratory, imaging, histopathologic, and genetic biomarkers that have been tested as tools to predict which patients are most likely to have a pCR after nCRT.