Neoadjuvant Chemo-Immunotherapy for Surgically Resectable Non-Small Cell Lung Cancer: Balancing Promise and Pitfalls

Definitive resection has long anchored curative therapy for early-stage and locally advanced non-small cell lung cancer (NSCLC), with adjuvant platinum doublets-and now adjuvant immune-checkpoint inhibitors (ICIs)-providing incremental gains in disease-free survival. Neoadjuvant chemo-immunotherapy may amplify benefit by expanding tumour-specific T-cell clones in situ, thereby addressing occult micrometastatic disease. Randomised trials (CheckMate 816, KEYNOTE-671, AEGEAN, CheckMate 77T) consistently improve event-free survival, pathological response, and in some cases overall survival over neoadjuvant chemotherapy alone. However, none compared directly with the long-standing standard of upfront surgery followed by adjuvant therapy, and 15-24 % of enrolled patients never reach the operating room-most commonly because of radiographic progression (5-8 %) or evolving surgical ineligibility. Consequently, roughly one in five potentially curable patients may lose their window for resection, highlighting a clinically meaningful tradeoff. These findings underscore three priorities: (i) rigorous prospective comparison of perioperative versus purely adjuvant systemic strategies-now underway in the PROSPECT-LUNG trial (NCT06632327); (ii) biomarker discovery to predict primary resistance and identify patients better served by immediate surgery; and (iii) nuanced shared decision-making that balances hoped-for systemic control against the risk of surgical attrition. Realising the full promise of ICIs in resectable NSCLC will require optimising both treatment sequencing and patient selection.