Pathologic response and nodal status guide adjuvant immunotherapy in non-small cell lung cancer after neoadjuvant chemoimmunotherapy: An eastern Asian cohort study.

Abstract

Background: The role of adjuvant immunotherapy following neoadjuvant chemoimmunotherapy for resectable non-small cell lung cancer (NSCLC) is a critical clinical question. This study aimed to develop a risk stratification model based on pathologic response and pathologic N stage after neoadjuvant therapy (ypN) status after neoadjuvant chemoimmunotherapy to identify patients who would derive the most benefit from adjuvant immunotherapy.

Methods: This multicenter retrospective study included 363 patients with resectable NSCLC (clinical stage IB-III) who underwent neoadjuvant chemoimmunotherapy followed by curative-intent surgery between January 2020 and December 2024. Patients were stratified into 4 groups based on major pathologic response (MPR) and ypN status. The efficacy of adjuvant immunotherapy on survival was evaluated for each group.

Results: After a median follow-up of 27.8 months, adjuvant immunotherapy conferred no survival benefit in the overall cohort; however, the proposed MPR-ypN classification effectively identified those patients most likely to benefit from adjuvant immunotherapy. The survival benefit from adjuvant immunotherapy was observed exclusively in the non-MPR ypN+ group, which demonstrated significantly improved recurrence-free survival and overall survival. Further analysis revealed that this survival benefit was driven by significant reductions in the risks of both distant metastasis and locoregional recurrence. In contrast, no survival benefit was observed in the MPR ypN0 group, non-MPR ypN0 group, or MPR ypN+ group, suggesting that adjuvant immunotherapy may be unnecessary for patients who achieve either a MPR or nodal clearance.

Conclusions: The MPR-ypN-based pathologic classification could effectively identify patients most likely to benefit from adjuvant immunotherapy. This approach established a selective treatment paradigm, reserving adjuvant immunotherapy for the non-MPR ypN+ population while potentially sparing the subgroup unlikely to derive additional benefit from unnecessary treatment and associated side effects.