Esophagectomy vs Active Surveillance in Clinical Complete Responders After Neoadjuvant Chemoradiation

The Surgery as Needed for Oesophageal Cancer (SANO) trial introduced active surveillance as a noninferior alternative to esophagectomy for patients with esophageal cancer who achieve a clinical complete response (cCR) after neoadjuvant chemoradiation (nCRT). However, concerns remain about recurrence risk, long-term survival, and quality-of-life trade-offs with organ-preserving strategies.

To evaluate the long-term comparative effectiveness of active surveillance vs standard esophagectomy in patients with cCR following nCRT for locally advanced esophageal cancer, using updated data from the SANO trial.

This decision analytical model used Markov modeling and probabilities and utility inputs derived from the SANO trial and existing literature. The base case was a 60-year-old male with good functional status and cT3N1M0 esophageal cancer achieving cCR after nCRT.

Standard routine esophagectomy vs active surveillance after neoadjuvant chemoradiation.

The primary outcome was quality-adjusted life-years (QALYs); the secondary outcome was life-years. Additional model scenarios explored (1) quality-of-life impacts of esophagectomy modeled as a time-varying covariate and (2) 2-year outcomes to align with the SANO trial time horizon. Sensitivity analyses evaluated recurrence probabilities and surgery-related quality-of-life trade-offs.

At 5 years, standard surgery yielded greater QALYs (1.74 vs 1.34; incremental gain of 0.40 QALYs or ~4.8 months in perfect health) and life-years (3.11 vs 2.41; incremental gain of 0.70 life-years or ~8.4 months) compared with active surveillance. However, at a 2-year horizon, active surveillance was preferred for QALYs (incremental gain of ~15 days), consistent with the SANO trial. Sensitivity analyses revealed the model favored active surveillance when the recurrence probability was less than 43%, the likelihood of local/resectable recurrence was greater than 94%, or the negative quality-of-life impact of esophagectomy was substantial. Modeling esophagectomy's quality-of-life impact as time limited further strengthened surgery's long-term QALY benefit.

This study found that while active surveillance offers short-term quality-of-life benefits and may be appropriate in select patients, particularly those at low recurrence risk or with high surgical risk, esophagectomy remains the preferred strategy for maximizing long-term survival and QALYs. These findings support a nuanced, individualized approach to post-nCRT management, balancing organ preservation with long-term oncologic outcomes.