Real-world adoption and pathological insights of neoadjuvant chemoimmunotherapy in resectable NSCLC: Single-institution experiences and perspectives.

Abstract

e20077 Background: Since March 2022, neoadjuvant or perioperative PD-(L)1 inhibitor plus platinum-based chemotherapy has become standard of care for resectable stage II–III non-small cell lung cancer (NSCLC). However, real-world implementation has been variable, and resistance mechanisms remain poorly understood, particularly among patients who fail to achieve pathologic complete response (pCR). We therefore evaluated institutional uptake, outcomes, and translational correlates of neoadjuvant therapy in resectable NSCLC. Methods: We retrospectively identified patients with resectable stage IB–IIIB NSCLC treated at a single academic center between January 2022 and December 2025 using surgical and pharmacy databases. Actionable genomic alterations (AGAs) were identified via next-generation sequencing (NGS) according to NCCN guidelines. Clinicopathologic characteristics, treatment patterns, surgical outcomes, and pathologic responses were summarized descriptively. To explore resistance mechanisms and inform adjuvant strategies, paired resected tumor and tumor-draining lymph node specimens were analyzed using Xenium single-cell spatial transcriptomics with a customized 480-gene panel. Results: Among 62 patients (median age at diagnosis 69.2 years; 58.1% male), 12 harbored AGAs and 4 progressed or were lost to follow-up. Forty-six (74.2%) received neoadjuvant therapy and 32 (51.6%) underwent surgical resection. Thirty-six patients received neoadjuvant chemoimmunotherapy, of whom 26 (72.2%) proceeded to surgery; among these, pCR was achieved in 7 (26.9%), pathologic downstaging without pCR in 14 (53.8%), stable disease in 4 (15.4%), and pathologic progression in 1 (3.8%). All 6 patients who received neoadjuvant chemotherapy without immunotherapy underwent surgery, with pCR in 1 (16.7%), pathologic downstaging without pCR in 4 (66.7%), and stable disease in 1 (16.7%). Preliminary spatial transcriptomic analyses of paired tumor and lymph node specimens (n = 6) demonstrated increased immune cell activation following chemoimmunotherapy. Resistant tumors showed higher RNA expression of TROP2, MET, HER2, NECTIN4, and EGFR compared with sensitive tumors; validation studies are ongoing. Conclusions: In this single-institution cohort, neoadjuvant chemoimmunotherapy demonstrated meaningful clinical effectiveness while highlighting persistent gaps in adoption. Translational analyses suggest actionable targets in resistant disease, underscoring the importance of personalized adjuvant strategies for patients with residual tumors. Overall, these findings emphasize the need for integrated multidisciplinary workflows and biomarker-driven approaches to improve outcomes in resectable NSCLC.