Impact of Phosphodiesterase-5 Inhibitor Use On Overall Survival in Sinonasal Malignancies: A Real-World Database Analysis

Background: Phosphodiesterase-5 (PDE5) inhibitors, commonly prescribed for conditions such as erectile dysfunction, exhibit established immunomodulatory effects in the tumor microenvironment. These effects include enhancing T-cell responses and suppressing the activity of myeloid-derived suppressor cells (MDSCs). Building upon this mechanistic rationale, we evaluated the association between PDE5 inhibitor use and survival outcomes in patients with sinonasal and nasopharyngeal cancers. Methods: This retrospective cohort study utilized the global federated TriNetX Research Network to compare overall survival in adult patients diagnosed with malignant neoplasm of the nasal cavity, accessory sinus, or nasopharynx. Two cohorts were defined: One cohort consisted of patients exposed to a PDE5 inhibitor after diagnosis. The second cohort consisted of non-exposed patients. Propensity score matching was performed to balance demographic (including gender) and clinical characteristics across cohorts. Kaplan-Meier survival analyses were conducted to determine 1-year, 3-year, and 5-year overall survival. Results: In Nasal Cavity (N=264 pairs), Accessory Sinus (N=363 pairs), and Nasopharynx (N=1,066) PDE5 inhibitor exposure was associated with significantly improved OS compared to controls across all three cancer types at all time points examined ( Table 1 ). The most notable survival benefit was observed in the nasopharynx cohort, which demonstrated the lowest Hazard Ratio (HR 0.433). Conclusion: PDE5 inhibitor use is consistently associated with statistically significant improvements in 1-year, 3-year, and 5-year overall survival in patients with accessory sinus, nasal cavity, and nasopharyngeal malignancies. These real-world, population-level data suggest that PDE5 inhibitors may offer an oncologic benefit in the treatment of sinonasal and nasopharyngeal cancers, supporting the rationale for future prospective studies investigating their role in oncologic therapy. Publication History Article published online: 27 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany