Pulmonary tuberculosis as a modifier of molecular features and survival in lung cancer patients

Pulmonary tuberculosis (TB) may influence lung tumor biology through chronic inflammation and immune dysregulation, but its clinical and molecular implications remain poorly understood in high TB-burden regions. This study aimed to evaluate the impact of active and prior TB on molecular characteristics and survival outcomes in patients with non-small cell lung cancer (NSCLC). We conducted a retrospective observational study including 219 patients diagnosed with NSCLC at the Instituto Nacional de Enfermedades Neoplásicas (INEN), Lima, Peru, between 2010 and 2023. Patients were classified as having active TB (a-TB, n=45) or prior TB (p-TB, n=174) according to clinical and radiologic data. Clinical, pathological, and molecular variables were collected. The primary endpoint was overall survival (OS); secondary endpoints included molecular profile distribution and progression-free survival (PFS). The median age was 57 years in a-TB and 64 years in p-TB. Adenocarcinoma was the predominant histology (94%). EGFR mutations and ALK rearrangements were found in 10.5% and 4.1% of the overall cohort, respectively. PD-L1 expression <1% was frequent (82.3%) and significantly associated with prior TB (p=0.004). In multivariable analysis, the absence of a driver mutation was independently associated with inferior OS in both a-TB (HR 2.94; p=0.046) and p-TB (HR 1.78; p=0.040) groups. Among patients with p-TB, longer TB exposure (>30 years) was associated with poorer OS (HR 1.47; p=0.039). In conclusion, pulmonary tuberculosis, particularly remote infection, was linked to immunosuppressive tumor profiles and decreased survival in NSCLC. These findings suggest that TB history may act as a biological modifier of tumor behavior and should be considered in the prognostic assessment and therapeutic planning of lung cancer patients in endemic regions.