Reconsidering the American Joint Committee on Cancer Eighth Edition TNM Staging Manual Classifications for T2b and T3 NSCLC

Introduction: The American Joint Committee on Cancer (AJCC) eighth edition TNM staging manual for NSCLC, derived from the International Association for the Study of Lung Cancer (IASLC) Staging Project, designates tumors with additional nodule(s) in the same lobe as T3. This study sought to externally validate the results of the IASLC, which showed a trend in improved survival for such tumors, but excluded treatment-based adjustment, by assessing whether these tumors have worse survival than T2b NSCLC. Methods: Overall survival of patients with T2b-T3, N0-3, M0 NSCLC (satisfying a single T descriptor of tumors >4 cm but ≤5 cm in greatest dimension [“T2b”], tumors >5 cm but ≤7 cm in greatest dimension [“T3-Size”], or tumors with additional nodule(s) in the same lobe [“T3-Add”]), according to the AJCC eighth edition, in the National Cancer Database (2010–2015), was evaluated using multivariable Cox proportional hazards modeling and propensity score matching. Results: 31,563 patients with T2b-T3, N0-3, M0 NSCLC met the study inclusion criteria. In multivariable-adjusted analysis, T3-Add tumors had improved overall survival compared with T3-Size tumors (Hazard Ratio = 0.86, 95% Confidence Interval: 0.82–0.89, p < 0.001) and similar survival compared with T2b tumors (Hazard Ratio = 1.04, 95% Confidence Interval: 0.97–1.12, p = 0.28). A propensity score-matched analysis of 2260 T3-Add and 2,260 T2b patients, well-balanced on 16 common prognostic covariates, including treatment type (surgery, chemotherapy, or radiation), revealed similar 5-year survival (53.4% versus 52.3%, p = 0.30). Conclusions: In this national analysis, T3-Add tumors had better survival than other T3 tumors and similar survival to T2b tumors. These findings may be taken into consideration for the AJCC ninth edition staging classifications.