Genomic and Clinical Impact of Smoking on Therapeutic Outcomes in Prostate Cancer: A Public Databases Analysis

BACKGROUND: In prostate cancer (PCa), smoking history is associated with more aggressive clinicopathological features, reduced efficacy of androgen deprivation therapy, and poorer overall survival (OS). However, its impact on survival outcomes in patients receiving taxane chemotherapy, poly ADP-ribose polymerase inhibitor (PARPi), or immune checkpoint inhibitor (ICI) therapy for PCa remains unclear. We compared the genetic profiles of smokers and non-smokers with PCa in several public databases to explore the potential influence of smoking on treatment outcomes. METHODS: We retrospectively collected data on smoking history, tumor characteristics, genomic information, treatment history, and survival outcomes from three public databases to investigate the role of smoking in PCa. Patients were categorized into smokers and non-smokers, and associations between smoking history and clinicopathological features, genetic profiles, and treatment outcomes were analyzed. Independent risk factors for OS were evaluated using multivariate Cox proportional hazard regression models. RESULTS: Smokers exhibited significantly higher Gleason score, clinical stage, tumor mutational burden, fraction genome altered, and microsatellite instability scores than non-smokers. The survival analysis revealed that smokers had significantly poorer OS than non-smokers in the overall, hormone therapy, and PARPi therapy cohorts. In contrast, no significant difference in OS was observed between the taxane chemotherapy and ICI therapy cohorts. Furthermore, multivariate Cox proportional hazard regression analysis identified smoking history as an independent risk factor for OS in the overall, hormone therapy, and PARPi therapy cohorts. Oncoplot analysis showed a significantly higher frequency of TP53 mutations and PTEN copy number alterations in smokers than in non-smokers. CONCLUSIONS: Smoking history was significantly associated with aggressive clinicopathological features and a poor prognosis in patients with PCa. Our findings suggest that smokers with PCa may receive greater benefit from the early administration of taxane chemotherapy in comparison to other treatment regimens.