Total Neoadjuvant Therapy for Rectal Cancer: Current Status and Future Directions

Purpose of Review The investigation of total neoadjuvant therapy has increased significantly in recent years, with a number of approaches being utilized in ongoing prospective studies, including (1) induction neoadjuvant chemotherapy (INCT), (2) consolidation neoadjuvant chemotherapy (CNCT), and (3) short-course radiation therapy (SC-RT) for locally advanced rectal cancer (LARC). Significant questions remain regarding the ideal sequence of a total neoadjuvant therapy (TNT) approach. Recent Findings Multiple prospective multi-institutional trials have evaluated the addition of multi-agent chemotherapy before or after neoadjuvant rectal cancer chemoradiation. In 2019, a multi-center randomized phase II trial from Germany, CAO/ARO/AIO-12, demonstrated better compliance and lower toxicities with CNCT in comparison to INCT. The OPRA study recently reported in ASCO 2020 improved organ preservation for CNCT, and similar 3-year disease-free survival (DFS) and distant metastasis-free survival (DMFS). RAPIDO reports higher rates of pathologic complete response (pCR) and lower rates of 3-year distant metastases (DM) for TNT compared to traditional treatment sequencing. Recent literature on TNT for LARC highlights the potential of this approach to enhance compliance, increase distant control and survival rates, and reduce toxicities. Further research is important to tailor treatment approaches to patients with LARC.