Validation and refinement of the ninth edition ypN descriptor in patients with non−small cell lung cancer receiving neoadjuvant therapy

Although the ninth edition N descriptors have been validated in upfront surgery populations, evidence supporting their validity in prognostic stratification in the neoadjuvant setting remains sparse. The study aimed to validate the prognostic relevance of exploratory quaternary N scheme refinement relative to the ninth edition N classification in postneoadjuvant non-small cell lung cancer (NSCLC). We identified 1,005 NSCLC patients who underwent complete resection following neoadjuvant therapy from four centers between May 2019 and September 2022. Prognostic difference of adjacent N categories' comparison regarding recurrence-free survival (RFS) and overall survival (OS) was estimated by the log-rank test and the Cox proportional hazards model. Decision curve analysis (DCA) was performed to quantify incremental survival prediction benefit. According to the ninth edition proposal, post-treatment pathologic (yp) N0, N1, N2a, and N2b were associated with a stepwise deterioration in prognosis, except between N1 and N2a (p=0.331 for OS; p=0.508 for RFS). In exploratory analyses, integration of multiple N1 stations involvement subcategory (N1b) with N2a due to prognostic homogeneity and comparable adjuvant treatment benefit, revealed significant distinction from single N1 station involvement (N1a) (p=0.019 for OS; p=0.018 for RFS) as well as from N2b (p<0.001 for both OS and RFS). DCA indicated exploratory quaternary descriptors comprising of N0/N1a/N1b+N2a/N2b yielded stronger prognostic relevance than the ninth edition classification. The ninth edition ypN classification was validated to demonstrate moderate prognostic discrimination in neoadjuvant population. Burden-directed and location-supplemented considerations for exploratory quaternary N scheme would provide novel insights into further ypN refinement.