Prediction of survival outcome in clinical stage II-III non-small cell lung cancer undergoing neoadjuvant chemoimmunotherapy: Role of ypN status vs PCR.

8056 Background: After FDA approval in 2022, neoadjuvant chemoimmunotherapy has become the standard of care for patients with non-small cell lung cancer (NSCLC) due to improved survival outcomes. Pathologic complete response (pCR) is often used as a predictor of patient survival following treatment. However, the role of posttreatment pathological nodal status (ypN) as a treatment predictor remains undefined. This study evaluates the predictive significance of ypN in comparison to established treatment predictors, such as pCR. Methods: Patients with clinical stage II-III NSCLC diagnosed in 2022 (n=29,017) who underwent neoadjuvant chemoimmunotherapy and resection (n=1,175) were identified using the National Cancer Database. Those with missing pCR data (n=16), pCR in tumor only (n=18), and those who died within one month of diagnosis were excluded. Chi-square tests were used for comparisons between groups. Survival analysis was performed using the Kaplan-Meier method, along with univariate and multivariable Cox proportional models. All tests were two-sided, and the statistical significance level used was 0.05. Results: The final cohort consisted of 720 patients divided into three groups: pCR-both (pCRb; ypT0N0; n=217; 30.1%), pCR-node (pCRn; ypN0; n=265; 36.8%), and residual viable in both (RVb; n=238; 33.1%). The pCRb group had a higher proportion of squamous cell carcinoma compared to the pCRn group (47% vs 34%, p<0.001). pCRn patients demonstrated a slightly higher rate of positive surgical margins (3% vs 1%, p=0.03) and subsequent use of adjuvant radiotherapy compared with pCRb (3% vs 1%, p=0.03). Kaplan-Meier analyses and Cox proportional hazards models showed similar overall survival (OS) between pCRb and pCRn groups (HR=1.37; p=0.363), while both had significantly higher OS compared with RVb (HRs 0.26 and 0.36; p<0.0001 for both). Subgroup analysis by number of examined lymph nodes showed comparable OS between pCRb and pCRn in patients with ≥10 lymph nodes examined (LN≥10; HR=1.36; p=0.47) and in those with <10 nodes examined (LN<10; HR=1.50; p=0.40). Conclusions: In clinical stage II-III NSCLC treated with neoadjuvant chemoimmunotherapy followed by resection, pCRb and pCRn demonstrated similar rates of OS, highlighting the significance of post-treatment pathological nodal status (ypN) as a potential predictor of OS in this population. Since pCRb requires invasive tissue sampling, using ypN as a predictor of OS would allow for more efficient risk stratification with overall less invasive testing.