Association of Statins with Biochemical Failure after Radiotherapy for Prostate Cancer

Abstract

There has been growing interest in the potential anticancer activity of statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) based on preclinical evidence of their antiproliferative, proapoptotic, and radiosensitizing properties. This study was undertaken to determine whether statins enhance the efficacy of Radiation Therapy (RT) in prostate cancer patients. Between 1988 and 2006, 719 men (median age 69) with prostate adenocarcinoma were treated at the University of Chicago with curative-intent radiotherapy. All patients had intact prostates, no distant metastases, and minimum follow-up of 2 years. The majority (80%) had <T2b disease with a median Gleason Score of 6 and a median PSA of 8.4 ng/mL (range, 0.2 to 242). The median radiation dose was 72 Gy delivered using external beam RT (84%), brachytherapy (9%), or a combination of both (7%). A total of 59% received Androgen Deprivation Therapy (ADT) for a median of 4 months. One hundred nine patients (15%) were on statins at initial consult, and 35 (5%) were started on statins after completing radiotherapy. Lipid panels were available in 85 of the patients taking statins with median lipid panel date 3 months prior to radiation start. Type of statin and statin doses were recorded, and doses were normalized to simvastatin equivalents for dose response analysis. Median follow-up was 50 months after RT. A PSA relapse was defined according to the Phoenix (nadir + 2) definition. On univariate analysis, statin use was associated with favorable biochemical outcomes using both Phoenix and ASTRO definitions (p < 0.0001 and p = 0.0167, respectively). This effect was seen in D'Amico low and high-risk groups (p = 0.0314 and p = 0.0070, respectively) with a trend in intermediate-risk patients (p = 0.0750). Across risk categories, statin use was associated with biochemical outcome to a greater degree than ADT (low-risk, p = 0.3482; intermediate risk, p = 0.3183; high-risk, p = 0.0544). On multivariate analysis, statin use (p < 0.0002), pretreatment PSA ≤8.4 (p = 0.0016), Stage <T2b (p = 0.0171), Gleason score <7 (p = 0.0261), and dose ≥7,400 cGy (p = 0.0474) were associated with biochemical outcome whereas ADT (p = 0.6026) was not. There was no significant relationship between LDL (p = 0.1382), HDL (p = 0.4576), or triglyceride level (p = 0.4767) and biochemical failure. There was, however, a trend for improved biochemical control with lower total cholesterol levels (p = 0.0531). There was no relationship demonstrated between statin type (p = 0.3553), statin dose (low or high, p = 0.1942), or timing of RT (at consult or during follow-up, p = 0.1654) and biochemical outcome. Statin use was associated with a significantly decreased risk of biochemical failure. Randomized clinical trials are warranted to further investigate this effect.