Will neoadjuvant chemoimmunotherapy complicate subsequent surgery compared with adjuvant chemoimmunotherapy?

Neoadjuvant chemoimmunotherapy has significantly improved pathological response rates in resectable non-small cell lung cancer (NSCLC). However, whether it increases surgical complexity compared with upfront surgery followed by adjuvant therapy remains clinically debated.

We retrospectively analyzed 121 NSCLC patients (81 neoadjuvant; 40 adjuvant) treated between 2021 and 2024. Inverse Probability of Treatment Weighting (IPTW) was applied to adjust for baseline imbalances. Surgical difficulty was quantified using a standardized 10-point scoring system. Multivariable logistic regression was then performed to identify independent risk factors for high-difficulty procedures (score >5).

IPTW successfully achieved balance across all baseline covariates. The neoadjuvant group exhibited significantly higher technical complexity than the adjuvant group (39.8% vs. 2.7% high difficulty; P < 0.001). Minimally invasive approach completion was substantially lower in the neoadjuvant group (57.8% vs. 93.5%), with significantly higher conversion rates (33.9% vs. 6.5%; P < 0.001). Anatomical challenges, particularly dense hilar adhesions and vascular fibrosis (the "frozen hilum"), were more prevalent after neoadjuvant treatment (P < 0.05). Multivariable analysis confirmed neoadjuvant therapy as the primary independent driver of increased surgical difficulty (OR: 0.032 for adjuvant vs. neoadjuvant; P < 0.001). Postoperative recovery metrics, including chest tube duration and hospital stay, remained comparable between groups after weighting (P > 0.05).

Neoadjuvant chemoimmunotherapy was associated with greater technical surgical difficulty and higher conversion rates compared with upfront surgery followed by adjuvant therapy. Despite these technical challenges, surgical resection remains safe and feasible, though it requires specialized thoracic expertise to manage complex anatomical alterations effectively.