Active surveillance after neoadjuvant chemoradiotherapy may be an alternative to surgery for some with esophageal cancer.
Esophagectomy is the keystone treatment for patients with esophageal cancer. This procedure, however, has a mortality rate of 1% to 5%, a complication rate of 59%, persisting symptoms and decreased quality of life [1]. Previously, the CROSS trial showed that neoadjuvant chemoradiotherapy improved survival and that 29% of patients had a complete pathological response after neoadjuvant chemoradiotherapy [2]. This imposed the dilemma of whether all patients should undergo standard surgery after neoadjuvant chemoradiotherapy, or whether active surveillance could provide an organ-sparing alternative strategy.
To answer this question, the phase 3 SANO noninferiority trial (NTR6803 8-11-2017, NCT05953181) included 309 participants with locally advanced esophageal cancer who had a complete pathological response after neoadjuvant chemoradiotherapy (defined as no residual disease at 6 and 12 weeks after neoadjuvant chemoradiotherapy). The participants were randomly assigned 1:1 to standard surgery or active surveillance. Participants in the active surveillance arm underwent a response evaluation every 6 weeks; surgery was only performed when a (residual) tumor was detected. The primary endpoint was overall survival (OS) from the day of complete pathological response. Noninferiority was defined as less than 15% difference in OS at 2 years between study arms. Dr. Berend van der Wilk (Erasmus Medical Center, the Netherlands) presented the first results [3].
After a median follow-up of 38 months, there was no statistically significant difference in OS between the arms (HR, 1.14; 95% CI, 0.74-1.78; P=0.55). At 2 years, OS in active surveillance was noninferior to standard surgery. In line with this, no statistically significant difference was observed in distant-free survival (HR, 1.35; 95% CI, 0.89-2.03; P=0.15), or distant metastases rate (OR, 1.45; 95% CI, 0.85-2.48; P=0.18). In the active surveillance arm, 35% of participants had persistent complete responses after 2 years.
Operative outcomes were comparable in both arms, except for the mean time to surgery. This means that patients with local regrowth during active surveillance could be operated on safely and successfully. At 6 and 9 months after randomization, global improvement in quality of life appeared to be statistically significant and clinically relevant in the active surveillance arm.
“These results suggest that active surveillance offers a potential alternative for surgery in patients with esophageal cancer who show pathological complete response after neoadjuvant chemoradiotherapy,” concluded Dr. Van der Wilk.
Copyright ©2023 Medicom Medical Publishers
