This IPD meta-analysis compared overall survival in stage-II NSCLC patients (AJCC TNM 8th ed.) receiving neoadjuvant chemoimmunotherapy (n=275, from phase-3 RCTs) versus upfront surgery (n=6,864–7,342, from pathological TNM 8th/9th-edition databases). Secondary comparisons evaluated neoadjuvant chemoimmunotherapy vs. chemotherapy alone for pathologic response, event-free survival, and surgical outcomes.
Chemoimmunotherapy improved OS vs. upfront surgery per the 8th-edition TNM database (HR=0.68, 95%CI 0.53–0.87, p=0.002), but not per the 9th-edition (HR=0.82, 95%CI 0.64–1.1, p=0.10). Vs. chemotherapy alone, chemoimmunotherapy yielded higher pCR (RR=6.19), major pathologic response (RR=3.08), better event-free survival (HR=0.66, p<0.001), and better OS (HR=0.68, p=0.01), with no difference in surgical complication rates.
- The chemoimmunotherapy arm is small (n=275) and extracted via the IPDfromKM method rather than directly from individual patient records, introducing reconstruction error. - Comparison vs. upfront surgery relied on historical TNM registry data, not a randomized control group, with potential for selection bias. - Results diverge depending on which TNM edition (8th vs. 9th) is used as the benchmark, limiting definitive conclusions.
For stage-II NSCLC, neoadjuvant chemoimmunotherapy offers better pathologic responses and event-free survival than chemotherapy alone, with no added surgical risk — but its OS benefit over upfront surgery remains uncertain and depends on staging classification. Clinicians should await better patient-selection tools before broadly shifting away from upfront surgery in this stage.
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