Clinical N Staging Subclassification for Stage III-N2 NSCLC Patients Undergoing Trimodality Therapy: A Good Beginning Is Half the Battle

Background: Lung cancer patients with stage III-N2 disease may benefit from the subclassification of nodal involvement before decision-making. We aimed to evaluate whether the clinical N descriptor subclassification predicts prognosis in patients undergoing trimodality therapy for stage III-N2 non-small cell lung cancer. Methods: Using our institutional registry between 2003 and 2019, we analyzed 899 consecutive patients with stage III-N2 non-small cell lung cancer undergoing neoadjuvant concurrent chemoradiotherapy followed by surgery. We subclassified clinical N2 into cN2a and cN2b on the basis of imaging and histopathologic results. Recurrence-free survival and overall survival were compared by N2 subclassification and separately by histologic type, using competing risks models and Cox proportional hazards models. Results: By the proposed N subclassification, 503 (56.0%) and 396 (44.0%) patients were assigned to cN2a and cN2b, respectively. During a median follow-up of 53.1 months, 492 patients had recurrence and 477 died. The hazard ratios for recurrence comparing cN2b with cN2a after adjustment for age, sex, comorbidities, clinical T category, and histologic type were 1.22 (95% CI, 1.03-1.46). The adjusted hazard ratios for mortality comparing cN2b to cN2a were 1.43 (1.19-1.71). When stratified by histologic type, cN2b had a higher risk of mortality compared with cN2a in both adenocarcinoma and squamous cell carcinoma. Conclusions: In our study evaluating the International Association for the Study of Lung Cancer's approach to subclassify the clinical N descriptor for stage III-N2 non-small cell lung cancer patients, cN2b had a higher risk of recurrence and mortality compared with cN2a, suggesting that clinical N subclassification may be a valuable predictor for stage III-N2 patients.