Active surveillance after neoadjuvant chemoradiotherapy in oesophageal cancer

Data from the SANO trial suggests that active surveillance after neoadjuvant chemoradiotherapy may be an alternative to surgery for some patients with oesophageal cancer.

Oesophagectomy is the keystone of treatment for patients with oesophageal cancer. This procedure, however, comes with a mortality rate of 1–5%, a complication rate of 59%, persisting symptoms, and decreased quality of life [1]. Previously, the CROSS trial (Netherlands Trial Register NTR487) showed that neoadjuvant chemoradiotherapy improved survival and that 29% of patients had a complete pathological response (49% of patients with squamous cell carcinoma and 23% with adenocarcinoma) 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 non-inferiority trial (NCT05953181) included 309 participants with locally advanced oesophageal 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 randomised 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 in case a (residual) tumour was detected. The primary endpoint was overall survival (OS) from the day of pathological complete response. Non-inferiority was defined as <15% difference in OS at 2 years between study arms. Dr Berend van der Wilk (Erasmus Medical Centre, 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 non-inferior to standard surgery (see Figure). 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 (odds ratio [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. However, no differentiation between adenocarcinoma and squamous cell carcinoma was made in the analysis.

Figure: Overall survival does not change with surgery for participants after neoadjuvant chemoradiotherapy in oesophageal cancer [3]



HR, hazard ratio. CI, confidence interval.

Operative outcomes were comparable in both arms, except for the mean time-to-surgery. This indicates that participants with local regrowth during active surveillance could be operated safely and successfully. At 6 and 9 months after randomisation, global improvement in quality of life appeared to be significantly different and clinically relevant in the active surveillance arm.

“These results suggest that active surveillance offers a potential alternative to surgery for patients with oesophageal cancer who show pathological complete response after neoadjuvant chemoradiotherapy,” concluded Dr Van der Wilk.

1. 
   
   1. Markar SR, et al. Ann Surg Oncol. 2020;27:718–723.
   2. Eyck BM, et al. J Clin Oncol. 2021;39(18):1995–2004.
   3. Van der Wilk BJ, et al. Neoadjuvant chemoradiotherapy followed by surgery versus active surveillance for oesophageal cancer (SANO-trial): A phase-III stepped-wedge cluster randomised trial. Abstract LBA75, ESMO 2023, 20–24 October, Madrid, Spain.

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Posted on 19 December 202319 December 2023