LBA75 - Neoadjuvant chemoradiotherapy followed by surgery versus active surveillance for oesophageal cancer (SANO-trial): A phase-III stepped-wedge cluster randomised trial

Background

One-third of patients with oesophageal cancer has a pathologically complete response after neoadjuvant chemoradiotherapy (nCRT) plus oesophagectomy. Active surveillance may be an alternative for patients with clinically complete response (CCR).

Methods

A noninferiority stepped-wedge cluster randomised trial was performed. Patients with CCR (i.e. no residual disease 6 and 12 weeks after nCRT) underwent active surveillance (surgery only when locoregional regrowth was detected) or standard surgery. Primary endpoint was overall survival (OS) from day of CCR. Noninferiority was defined as Hazard Ratio (HR) <1.77 for mortality in active surveillance after two years. Secondary endpoints were operative outcomes, disease-free survival (DFS), distant dissemination rate and quality of life (HRQOL, EORTC QLQ-C30).

Results

Some 198 patients underwent active surveillance and 111 patients underwent standard surgery. Median follow-up was 34 months in active surveillance and 50 months in standard surgery. OS in active surveillance was noninferior to standard surgery (HR 0.88, 95% upper boundary 1.40, p = 0.007). During active surveillance, 69 patients (35%) maintained CCR, 96 patients (48%) developed locoregional regrowths, and 33 patients (17%) developed distant metastases. R1 rate was 2% in both groups and postoperative 90-day mortality was 4% (active surveillance) versus 5% (standard surgery). Median DFS for active surveillance was 35 (95% CI 31 – 41) versus 49 months (95% CI 38 – NA) for standard surgery (HR 1.35, 95% CI 0.89 – 2.03, p = 0.15). At 30 months after nCRT, 43% of patients with active surveillance versus 34% with standard surgery developed distant metastases (OR 1.45, 95% CI 0.85 – 2.48, p = 0.18). HRQOL was statistically significantly better at six (p = 0.002) and nine months (p = 0.007) for active surveillance.

Conclusions

After a follow-up of two years, patients undergoing active surveillance had noninferior OS and improved short-term HRQOL compared to standard surgery. Postponed esophagectomy for locoregional regrowth was safe. Extended follow-up is required to assess long-term efficacy of active surveillance.

Clinical trial identification

NTR6803 8-11-2017.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

This study was funded by the Dutch Cancer Society (KWF) and Netherlands Organisation for Health Research and Development (ZonMw).

Disclosure

All authors have declared no conflicts of interest.