The role of adjuvant therapy in non-pCR patients after neoadjuvant chemoimmunotherapy: Comparison with neoadjuvant chemoradiotherapy for ESCC.
Abstract
Background
Neoadjuvant chemoimmunotherapy (NCIT) is increasingly used for locally advanced esophageal squamous cell carcinoma (ESCC), but the role of adjuvant therapy-particularly immunotherapy-after NCIT remains undefined.
Methods
This single-institution retrospective study included 458 ESCC patients treated with neoadjuvant chemoradiotherapy (NCRT, n = 187) or NCIT (n = 271) followed by esophagectomy (2021-2024). A 1:1 propensity score matching (PSM) based exclusively on pretreatment characteristics was used to compare the neoadjuvant strategies. To assess postoperative adjuvant therapy while addressing guarantee-time bias and subgroup imbalance, a 60-day landmark analysis with separate propensity-score overlap weighting within NCRT and NCIT was performed. Primary endpoints were 2-year overall survival (OS) and disease-free survival (DFS).
Results
After pretreatment-only PSM (157 pairs), NCRT and NCIT showed similar 2-year OS (78.3% vs. 77.6%, P = 0.853) and DFS (70.9% vs. 70.2%, P = 0.996), despite a significantly higher pCR rate with NCRT (37.6% vs. 13.4%, P < 0.001). In the 60-day landmark analysis, adjuvant therapy was associated with a lower summary DFS hazard in the NCIT overlap population (HR, 0.62; 95% CI, 0.39-0.99; P = 0.044), but not with OS. Among NCIT non-pCR patients, the summary DFS association remained (HR, 0.59; 95% CI, 0.35-0.99; P = 0.045) and was strongest during early follow-up. Corresponding NCRT estimates were not statistically significant.
Conclusions
NCIT was associated with survival comparable to NCRT despite a lower pCR rate. Among patients who did not achieve pCR after NCIT, postoperative adjuvant therapy was associated with a lower early DFS hazard, whereas a statistically significant association was not demonstrated after NCRT. These subgroup findings are exploratory and do not establish a differential treatment effect between neoadjuvant regimens. Prospective validation is warranted.