Association of Adjuvant Immunotherapy with Improved Survival for Stage II-III Esophageal Cancer: 4-Year National Perspective

The recent ground-breaking CheckMate 577 trial demonstrated that patients with esophageal cancer (EC) who underwent neoadjuvant chemoradiation and surgery followed by adjuvant immunotherapy experienced significantly improved survival. However, nationwide utilization of adjuvant immunotherapy remains unknown, as does the impact of such treatment on overall survival outside of the clinical trial setting.

We identified all patients ≥ 18 years diagnosed with clinical stage II-III EC from January 2018 to December 2022 within the National Cancer Database. Only patients who underwent neoadjuvant chemoradiation and definitive esophagectomy with complete resection, found to have residual pathologic disease, were included. Patients were stratified by receipt of adjuvant immunotherapy into immunotherapy or no-immunotherapy cohorts.

Of 1367 patients, 342 (25%) received adjuvant immunotherapy. Utilization of immunotherapy in the adjuvant setting dramatically increased from 3% in 2018 to 50% in 2022 (P < 0.001). Following comprehensive risk adjustment, receipt of adjuvant immunotherapy was associated with significantly reduced mortality hazard at 1 (HR 0.25, CI 0.15-0.41) and 3 (HR 0.60, CI 0.44-0.81) years. Upon restricted mean survival time (RMST) analysis, patients who received adjuvant immunotherapy were found to experience 4.61 additional months of survival time over 3 years of follow-up (ΔRMST 4.61 months, CI 1.94-7.28).

Utilization of adjuvant immunotherapy among patients with locally advanced residual disease following multimodal treatment has dramatically increased since the Checkmate 577 trial. In this national study, patients who received adjuvant immunotherapy experienced ~5 months of survival benefit. Yet, with such an incremental impact on survival, additional studies are needed to further optimize the multimodal perioperative treatment of patients with EC.