Does a statin a day keep prostate cancer (PC) away?: Statin use and disease progression in patients receiving androgen deprivation therapy (ADT) after radical prostatectomy (RP) in SEARCH.

Abstract

5091 Background: Prior studies suggest statin use may improve PC outcomes, including PC specific mortality (PCSM) and disease progression in patients receiving ADT. However, prior studies compared patients taking vs not taking statins at the time of ADT, ignoring that many statin non-users initiate statins later on. We evaluated the association between statin use and PC outcomes using both baseline (yes/no) and time-dependent exposure definitions in patients initiating ADT after RP. Methods: We conducted a retrospective cohort study of 9,931 patients with PC treated with RP between 1988 and 2020 at 9 VA hospitals from SEARCH Database. Patients who received ADT for biochemical recurrence after 2000 were included. Those with known metastasis prior to ADT or missing covariates of interest were excluded. Characteristics at ADT were stratified by statin use at time of ADT and compared with rank-sum for continuous variables and chi-square for categorical. Univariable and multivariable Cox models tested associations between statin use at ADT and time to metastasis, castration-resistant PC (CRPC), PCSM and all-cause mortality (ACM), adjusted for clinicopathological variables. As ~50% of non-statin users initiated statins after ADT, additional models treated statin use as time-dependent covariate. Results: Among 1,274 patients treated with ADT, 784 (62%) used statins at time of ADT. Users were older (median 67 vs 65), initiated ADT in more recent years (median 2013 vs 2010), had longer time from RP to ADT (median 39 vs 21 months), and had higher obesity rates (38% vs 25%). PC characteristics were similar between groups, except users had lower rates of positive nodes (11% vs 17%) and seminal vesicle invasion (28% vs 33%). Statin use at ADT was not significantly associated with time to metastasis, CRPC, PCSM or ACM, though HRs indicated lower risk for statin users (all HRs 0.89-0.98, all p>0.2; see table). On time-dependent multivariable analysis, statin use was significantly associated with lower risk of CRPC (p=0.019), PCSM (p=0.020) and ACM (p<0.001). Similar results were seen for metastases, though this did not reach significance (p=0.058) (see table). Conclusions: Statin use at ADT was not associated with PC outcomes after RP. However, accounting for statin initiation during ADT, statin use was associated with notably lower rates of CRPC, PCSM and ACM, with a trend towards reduced metastasis. These findings support the potential role of statins in slowing PC progression and highlight the need for prospective randomized trials of statins in patients initiating ADT. Outcome Statin at ADT, HR (95% CI) p Time-varying statin, HR (95% CI) p Metastasis 0.92 (0.71, 1.20) 0.541 0.74 (0.55, 1.01) 0.058 CRPC 0.95 (0.73, 1.24) 0.702 0.69 (0.51, 0.94) 0.019 PCSM 0.98 (0.70, 1.39) 0.920 0.62 (0.42, 0.93) 0.020 ACM 0.89 (0.73, 1.08) 0.229 0.51 (0.40, 0.64) <0.001