Surgical and safety outcomes in patients with non-small cell lung cancer receiving neoadjuvant chemoimmunotherapy versus chemotherapy alone: A systematic review and meta-analysis

Neoadjuvant immune checkpoint blockade (ICB) combined with chemotherapy has improved survival outcomes in locally-advanced non-small cell lung cancer (NSCLC). However, its impact on surgery has not been fully elucidated. We performed a systematic review and meta-analysis to compare surgical outcomes between neoadjuvant chemoimmunotherapy and chemotherapy alone in resectable NSCLC. PubMed and Embase were searched to select randomized controlled trials (RCTs) evaluating neoadjuvant ICB therapy for resectable NSCLC. The risk difference (RD) and odds ratio (OR) of outcomes such as surgical and R0 resection rates, overall complication rates, treatment-related adverse events (TRAEs), and AEs leading to cancellation of surgery were pooled using the random-effect model meta-analysis. We also evaluated the correlations between overall survival (OS) and surgical and safety outcomes. Eight RCTs with 3,387 patients were analyzed. Neoadjuvant chemoimmunotherapy was associated with improved surgical resection (RD 4.52 %, 95 % confidence interval [CI] 0.95 %-8.09 %, p = 0.01) and R0 resection (RD 4.04 %, 95 % CI 1.69 %-6.40 %, p = 0.0008) without increasing overall complications (RD -0.13 %, 95 % CI -5.14 %-4.88 %, p = 0.96), but an increase in surgery cancellation due to AEs (RD 1.15 %, 95 % CI 0.25 %- 2.05 %; p = 0.01) and grade 3-4 TRAEs (RD 3.42 %, 95 % CI 0.33 %-6.52 %, p = 0.03). OS did not show a direct significant correlation with surgical outcomes or TRAEs. Neoadjuvant chemoimmunotherapy improves resection rates but increases high-grade TRAEs and AEs leading to surgery cancellation. Nevertheless, incorporating ICB into neoadjuvant approach appears reasonable by improving surgical outcomes, potentially leading to improved survival in patients with locally-advanced NSCLC.