Impact of PDE5 inhibitor use on survival outcomes in male-predominant cancers: A propensity score-matched analysis.

Abstract

e23325 Background: Phosphodiesterase-5 (PDE5) inhibitors, commonly prescribed for erectile dysfunction, exhibit immunomodulatory properties that may affect cancer outcomes by reducing myeloid-derived suppressor cell activity and enhancing T-cell responses. Previous studies suggest that PDE5 inhibitors reprogram the tumor microenvironment and augment antitumor immunity, particularly by promoting CD8+ T-cell infiltration and suppressing immunosuppressive pathways. Methods: Cancers were identified using the SEER database based on a male-to-female incidence ratio threshold of 3:1. An association analysis was performed using the TriNetX Research Network to evaluate the relationship between PDE5 inhibitor use and overall survival (OS) in male-dominant solid organ cancers. Included cancers were prostate, bladder, colon, esophageal, hypopharyngeal, laryngeal, tonsillar, and testicular cancers. Patients were categorized into those prescribed PDE5 inhibitors at least one day after the initial cancer diagnosis (Cohort A, n = 3,978) and those with no history of PDE5 inhibitor prescriptions (Cohort B, n = 3,978). Propensity score matching was performed using 20 demographic and clinical variables, including age, ethnicity, and oncological staging variables (AJCC TNM classifications: T, N, and M; and stages 0–4). Kaplan-Meier survival analyses were conducted for 1-, 3-, and 5-year OS. Results: One-year OS was significantly higher in Cohort A compared to Cohort B, with survival probabilities of 98.22% versus 88.35% (HR 0.144, 95% CI 0.111–0.186, p = 0.000), as confirmed by the Log-Rank Test (χ² = 287.663, df= 1, p = 0.0001). The proportional hazards assumption for 1-year OS was tested and met (HR χ² = 3.064, df= 1, p = 0.080). At 3 years, Cohort A exhibited improved OS compared to Cohort B, with survival probabilities of 94.77% versus 75.54% (HR 0.185, 95% CI 0.157–0.218, p = 0.000), supported by the Log-Rank Test (χ² = 509.201, df= 1, p = 0.0001). The proportional hazards assumption for 3-year OS was also met (HR χ² = 10.087, df= 1, p = 0.001). At 5 years, Cohort A demonstrated significantly greater OS than Cohort B, with survival probabilities of 91.77% versus 68.39% (HR 0.209, 95% CI 0.181–0.240, p = 0.000), as shown by the Log-Rank Test (χ² = 577.844, df= 1, p = 0.000). The proportional hazards assumption for 5-year OS was tested and met (HR χ² = 24.133, df= 1, p = 0.0001). Conclusions: PDE5 inhibitor use is associated with improved 3- and 5-year overall survival in patients with male-dominant cancers. Although prior research suggests that PDE5 inhibitors may exert immunomodulatory effects, the specific mechanisms contributing to the observed survival benefits in this study are not yet understood and require further exploration. These findings highlight the importance of additional studies to confirm these associations and investigate the potential therapeutic role of PDE5 inhibitors in oncology.