Statin exposure and clinical outcomes in metastatic prostate cancer: A propensity-matched TriNetX cohort study.

e17087 Background: Statins have pleiotropic biologic effects and have been hypothesized to favorably influence prostate cancer outcomes. However, their association with outcomes during contemporary androgen-ablative systemic therapy in metastatic disease remains uncertain. Methods: We conducted a retrospective cohort study using the TriNetX Research Network (2014–2024). Men with metastatic prostate cancer initiating androgen deprivation therapy and/or androgen receptor pathway inhibitors were classified by baseline statin exposure (active statin use within 6 months before and on the index date) versus no statin use (none from 6 months before through 6 months after index). Cohorts were propensity score–matched 1:1 for demographics, metastatic sites, comorbidities, and baseline cardiometabolic/oncologic medications. Outcomes from day 1 post-index were overall survival (OS), treatment switching (docetaxel or lutetium Lu 177 vipivotide tetraxetan), skeletal-related events (SRE), and major adverse cardiovascular events (MACE) at 1 and 5 years using Kaplan–Meier analysis with log-rank testing. HRs with 95% CIs were generated by TriNetX. Results: Before matching, 5,071 statin users and 11,143 nonusers were identified; after propensity score matching, 3,565 patients were included per cohort. At 1 year, OS was similar (90.35% vs 89.24%; HR 0.887, 95% CI 0.762–1.032; log-rank p = 0.120). MACE was higher with statins (92.33% vs 93.76% event-free; HR 1.258, 95% CI 1.049–1.510; p = 0.015). At 5 years, statin exposure was associated with modestly higher OS (66.17% vs 63.48%; HR 0.903, 95% CI 0.821–0.994; p = 0.037), while MACE remained higher (79.85% vs 81.53% event-free; HR 1.154, 95% CI 1.010–1.318; p = 0.035). Conclusions: In this propensity-matched real-world cohort of men with metastatic prostate cancer receiving contemporary androgen-ablative therapy, baseline statin exposure was associated with a small OS advantage at 5 years but not at 1 year, without differences in treatment switching or skeletal events. Higher MACE rates suggest residual confounding by cardiovascular risk and emphasize cardio-oncology optimization. Prospective studies are needed to clarify causality. Outcomes comparing statin vs. no-statin groups. Outcome (Time Horizon) Statin KM % No-Statin KM % HR (95% CI) p (log-rank) OS (1 year) 90.35 89.24 0.887 (0.762–1.032) 0.120 Treatment switch (1 year) 91.78 92.38 1.085 (0.915–1.287) 0.347 SRE (1 year) 96.13 96.38 1.081 (0.842–1.388) 0.543 MACE (1 year) 92.33 93.76 1.258 (1.049–1.510) 0.015 OS (5 years) 66.17 63.48 0.903 (0.821–0.994) 0.037 Treatment switch (5 years) 84.34 84.25 1.011 (0.880–1.162) 0.875 SRE (5 years) 91.26 90.58 0.985 (0.816–1.189) 0.878 MACE (5 years) 79.85 81.53 1.154 (1.010–1.318) 0.035