Occult primary non-small cell lung cancer (NSCLC) with mediastinal involvement is a known but rare clinical condition. Very limited retrospective data are available in the literature. Its prognosis and response to systemic chemotherapy have not been investigated with large scale data.

Using National Cancer Database (NCDB), cases that had undergone radiation therapy without surgery for N2-3M0 NSCLC were selected. Demographics and survival data were compared between T0 and T1-4 groups. Survival analyses were conducted with Kaplan-Meier and log-rank tests. Cox proportional hazard models were used for univariate and multivariate analyses.

Between 2004 and 2016, 84,263 and 458 cases met criteria for unresectable stage III NSCLC with T1-4 and T0 stage, respectively. T0 status was associated with younger age, recent diagnosis (year 2010-2016), adenocarcinoma histology, N3 stage, and use of chemotherapy. Survival analysis demonstrated that those with T0 status had prolonged overall survival as compared to T1-4 counterparts in both overall and chemotherapy groups (p < 0.0001 for each). Five-year overall survival rates for T0 and T1-4 groups were 30.5% and 12.7% in all groups, and 33.6% and 14.6% in chemotherapy groups, respectively. Propensity score matching also demonstrated a statistically significant difference in overall survival (p < 0.0001). These findings are confirmed by independent analysis using Surveillance, Epidemiology, and End Results Program (SEER).

This large hospital-based study demonstrates the favorable prognosis for T0 status in the setting of unresectable stage III NSCLC. Researchers may consider it as distinct stage (e.g., stage IIC) for future studies.