Single-center phase 3 trial of neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy for initially unresectable locally advanced colon cancer

Neoadjuvant chemotherapy (NACT) is commonly used to downstage the tumor and improve the R0 resection rate in locally advanced colon cancer (LACC). Neoadjuvant chemoradiotherapy (NACRT) is the standard treatment for locally advanced rectal and esophageal cancers, but its benefits in LACC is not known. A phase 3 trial at Sun Yat-sen University (Guangzhou, China) compared NACRT versus NACT in patients with initially unresectable LACC. Patients were randomized to four 3-week cycles of XELOX (NACT) or four 3-week cycles of XELOX plus daily irradiation (NACRT) followed by resection and adjuvant chemotherapy for patients who developed resectable disease. The R0 resection rate was 80% with NACRT versus 20% with NACT. NACRT compared with NACT was associated with improved overall survival, progression-free survival, and local control. Both NACT and NACRT were well tolerated, with no significant differences in severe adverse events. There were no grade 5 treatment-related adverse events. The authors conclude that addition of radiation to NACT for initially unresectable LACC was associated with increased R0 resection rate and improvement of PFS and OS.