796. P02.05 NEOADJUVANT CHEMORADIOTHERAPY FOLLOWED BY ACTIVE SURVEILLANCE VERSUS STANDARD SURGERY FOR OESOPHAGEAL CANCER (SANO-TRIAL): A MULTICENTRE STEPPED-WEDGE CLUSTER-RANDOMISED NONINFERIORITY TRIAL

Abstract Background One of the standard treatments for patients with locally advanced oesophageal cancer is neoadjuvant chemoradiotherapy followed by oesophagectomy. Of these patients, 29% have a pathologically complete response. Active surveillance may be an alternative for patients with clinically complete response (i.e. no residual tumour detected using clinical response evaluations). Methods A multicentre stepped-wedge cluster-randomised noninferiority trial was performed in twelve Dutch hospitals. Patients with a clinically complete response were included, determined with endoscopic biopsies, endoscopic ultrasound with fine-needle aspiration and PET-CT. Afterwards, patients underwent active surveillance or standard surgery. Primary endpoint was overall survival, which was analysed according to modified intention-to-treat (allowing cross-over at time of clinically complete response), traditional intention-to-treat and according to histology. Noninferiority was defined as two-year survival rate for active surveillance 15% below standard surgery. Results Between November 8, 2017 and January 17, 2021, 1115 patient were screened of whom 309 patients were included, 198 underwent active surveillance and 111 standard surgery. Two-year overall survival for active surveillance was noninferior to standard surgery (3% higher, 95% upper boundary 7% lower). There were no significant differences in overall survival according to modified intention-to-treat analysis (HR:1.14, 95%CI:0.74–1.78, p=0.55), traditional intention-to-treat analysis (HR:0.83, 95%CI:0.53–1.31, p=0.42) or in the analysis according to histology. Eighty-three patients from the active surveillance group underwent postponed surgery with postoperative complications and radicality comparable to standard surgery. Sixty-nine patients had persistent CCR and 22 patients developed distant metastases within six months, prior to surgery. Median disease-free survival for active surveillance was 35 (95%CI 28–NR) versus 49 months (95%CI 31–NR) for standard surgery (HR1.25, 95%CI:0.83–1.89,p=0.29). Health-related quality of life was better at six and nine months for active surveillance. Conclusion Overall survival following active surveillance for oesophageal cancer is noninferior compared to standard surgery after two years. Postponed oesophagectomy for locoregional regrowth appeared safe. Of 198 patients who underwent active surveillance, 91 patients (46%) had been spared oesophagectomy, resulting in improved HRQOL. For the long-term efficacy of active surveillance, extended follow-up is required.