Pathologic complete response after neoadjuvant immunochemotherapy: Persistent recurrence risk highlights the need for stratified management.

Abstract

Pathologic complete response (pCR) after neoadjuvant therapy predicts favorable outcomes in esophageal squamous cell carcinoma (ESCC). In this era of neoadjuvant immunochemotherapy (nICT), the prognosis of patients achieving nICT-induced pCR remains unclear. This study aimed to characterize recurrence patterns and identify prognostic factors in this population. A multicenter retrospective cohort study was conducted across 26 Chinese centers from 2019 to 2023. Patients with ESCC who underwent surgery after nICT and achieved pCR were included. Prognostic factors for recurrence-free survival (RFS) and overall survival (OS) were evaluated using Cox regression analysis. Among 2135 patients receiving nICT, 474 (22.2%) achieved pCR. After a median follow-up of 32.8 months, 60 patients (12.7%) experienced recurrence, with a median interval of 17.8 months (interquartile range, 8.7-26.7) after surgery. Most recurrences (75%) occurred within 2 years, predominantly as distant metastases (63.3%), with the lung being the most common site. The 2-year RFS and OS were 89.6% and 92.1%, respectively. Advanced clinical nodal stage (cN2-3) was identified as an independent prognostic factor for inferior RFS (adjusted hazard ratio, 1.83; 95% CI, 1.10-3.05; P = .02) but not OS, whereas adjuvant treatment was not associated with improved survival (adjusted hazard ratio, 1.29; 95% CI, 0.69-2.42; P = .42). Patients with ESCC achieving pCR after nICT exhibited excellent short-term survival but a persistent risk of distant recurrence. Advanced clinical nodal stage is associated with higher recurrence risk, which warrants further validation. Risk-adapted postoperative management may be preferable to routine adjuvant treatment.