Abstract 4468: Role of statins and PSA nadir after androgen-deprivation therapy in overall survival of patients with metastatic prostate cancer
Authors: Siddiqui Salma , Durbin-Johnson Blythe P. , Yap Stanley A. , White Ralph W. deVere , Ghosh Paramita M. 
Published: August 2019

Abstract
Statins are known to reduce prostate cancer (CaP) aggressiveness in both localized and metastatic disease. Studies have indicated that the use of statin drugs to lower cholesterol levels was associated with decreased risk of localized CaP, less frequent high grade CaP and lower CaP volume, suggesting that statin use has a protective effect against localized CaP. However, less is known about a role for statins in metastatic CaP (mCaP). While it is known that hypercholesterolemia is associated with the development of castration resistant prostate cancer (CRPC) after androgen deprivation therapy (ADT) in patients with bone metastasis, it is not known whether the sequence of statin and ADT affects outcome. Charts of 162 patients with mCaP treated at the VA Northern California Health Care System (VANCHCS) with ADT and statins between 1992 and 2016 were analyzed. Overall survival (OS) was followed until 12/2016. Dates were noted from the medical records entered into the Computerized Patient Record System (CPRS). Time to event outcomes (with the exception of time to Nadir PSA, which was not censored) were analyzed using Cox proportional hazard models. PSA Nadir and time to PSA Nadir were analyzed using linear models, with outcomes log transformed. All models include age at PSA diagnosis and year of metastatic diagnosis as covariates. Of the 162 total patients, 110 were on ADT following biochemical recurrence (BCR) at the time of diagnosis with distant metastasis (ADT before mets, ABM) while 50 were diagnosed with a distant metastatic lesion at the time of ADT administration (mets before ADT, MBA). 46.3% of the patients did not receive statin treatment whereas 41.4% received statins prior to diagnosis with distant metastasis, and 12.3% started statins after metastasis diagnosis (29% prior to ADT treatment and 24.7% after starting on ADT). There was no effect of statins on OS among those who had a diagnosis of metastasis prior to initial ADT (MBA group). On the other hand, among those who developed metastases while on ADT (ABM group), statin use significantly increased OS (based on the time of metastasis diagnosis). However, within this group, the largest benefit was in the patients that received statins after starting ADT (HR = 0.51, p=0.022). The same group (subgroup within the ABM group who initiated statins after ADT) also took longer to reach PSA nadir following ADT compared to those who never received statins (R=1.79, p=0.031) and also took longer to be diagnosed with mCaP following ADT compared to those who had never been (HR=0.45, p=0.003). These advantages were not seen in patients in the ABM group who were already on statins at the time of ADT initiation, and no advantages of statins were seen in the MBA group. Our data indicate that treatment with statins initiated after the patient has undergone ADT is beneficial to patients who develop distant metastases while on ADT treatment.
Citation Format: Salma Siddiqui, Blythe P. Durbin-Johnson, Stanley A. Yap, Ralph W. deVere White, Paramita M. Ghosh. Role of statins and PSA nadir after androgen-deprivation therapy in overall survival of patients with metastatic prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4468.