Multicenter non-inferiority phase 3 trial of neoadjuvant chemoradiotherapy followed by active surveillance for esophageal cancer

A substantial proportion of patients with esophageal cancer have a pathological complete response after neoadjuvant chemoradiotherapy (CRT) and esophagectomy. The cluster-randomized, noninferiority phase 3 SANO trial, at 12 centers in The Netherlands, investigated safety of active surveillance for patients with clinical complete response after neoadjuvant CRT (no tumor detected with endoscopy, ultrasound, and PET-CT). Patients were randomized to active surveillance (n=198) or standard surgery (n=111). Median follow-up was 38 months (IQR 32-48). Two-year overall survival (primary endpoint) was 74% in the active surveillance group versus 71% in the surgery group. The frequency of postoperative complications and postoperative mortality after standard surgery or postponed surgery after active surveillance was similar between groups. The authors conclude that overall survival after active surveillance for esophageal cancer was non-inferior compared with standard surgery after 2 years. For the long-term efficacy of active surveillance, extended follow-up is required.