Sequencing of Total Neoadjuvant Therapy for Rectal Cancer

The use of total neoadjuvant treatment — the administration of chemoradiotherapy (CRT) and chemotherapy (CT) prior to surgery — has been shown to improve rates of clinical and pathologic complete response (PCR). However, the optimal scheduling of CRT and CT in this setting has not been established.

The prior multicenter, randomized, phase II trial of 306 German patients with stage II or III rectal cancer receiving total neoadjuvant therapy (CAO/ARO/AIO-12; J Clin Oncol 2019; 37:3212) showed that a higher rate of PCR (the primary endpoint) was achieved when CRT (5-FU and oxaliplatin plus radiotherapy) was given before CT versus the reverse sequence (25% vs. 17%), with comparable surgical outcomes. More than 80% of patients had clinical stage …