Document Type

Article

Publication Date

1-1-2025

Comments

This article is the author's final published version in Frontiers in Oncology, Volume 15, January 2025, Article Number 1720304.

The published version is available at https://doi.org/10.3389/fonc.2025.1720304. Copyright © Uralov, Harrington, Samarah, Walia, Aweeda, Mustafa, Kumar, Briskin, Jackson, Mastrolonardo and Luginbuhl.

Abstract

INTRODUCTION: Phosphodiesterase-5 (PDE5) inhibitors, commonly prescribed for erectile dysfunction, may exhibit immunomodulatory properties by reducing myeloid-derived suppressor cell activity and enhancing T-cell responses. This study evaluated the association between PDE5 inhibitor use and overall survival (OS) in male-predominant solid organ malignancies.

METHODS: Male-predominant solid tumors were identified using male-to-female incidence ratio ≥3:1 in SEER database: prostate, bladder, colon, esophageal, hypopharyngeal, laryngeal, tonsillar, and testicular cancers. Using the TriNetX Research Network, we compared male patients prescribed PDE5 inhibitors within 6 months of cancer diagnosis to those without PDE5 exposure. Propensity score matching (PSM) was performed on demographic, clinical, and oncologic variables. OS was assessed in a combined pan-cancer cohort, stratified by overall stage, and subgroups of included cancers. Kaplan-Meier survival analyses were conducted for 1-, 3-, and 5-year OS from diagnosis.

RESULTS: After PSM, 108,630 patients were included in each arm of the pan-cancer analysis. PDE5 inhibitor exposure was associated with significantly improved OS at 1, 3, and 5 years compared with controls (5-year OS 93.8% vs 86.6%; HR, 0.42 [95% CI, 0.41-0.44]). Stratified analyses demonstrated significantly improved OS across all four stages, with hazard ratios ranging from 0.40 to 0.57. Subgroup analyses by tumor site likewise showed statistically significant improvement in OS for every included cancer type, with hazard ratios ranging from 0.35 to 0.70.

CONCLUSIONS: PDE5 inhibitor use was consistently associated with improved OS across all male-predominant cancers, including in stage-stratified analyses. These findings support further investigation into the potential role of PDE5 inhibitors in cancer outcomes.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

41450924

Language

English

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