Purpose There has been growing interest in the potential anticancer activity of statins based on preclinical evidence of their antiproliferative, proapoptotic, and radiosensitizing properties. The primary objective of this study was to determine whether statin use is associated with improved clinical outcomes in patients treated with radiotherapy (RT) for prostate cancer. Patients and Methods In total, 691 men with prostate adenocarcinoma treated with curative-intent RT between 1988 and 2006 were retrospectively analyzed. Of those, 189 patients (27%) were using statins, either during initial consultation or during follow-up. Lipid panels were collected (n = 298) a median of 5 months before RT start. Median follow-up was 50 months after RT. Results Statin use was associated with improved freedom from biochemical failure (FFBF; P < .001), freedom from salvage androgen deprivation therapy (FFADT; P = .0011), and relapse-free survival (RFS; P < .001). Improved FFBF for statin users was seen in low-, intermediate-, and high-risk groups (P = .0401, P = .0331, and P = .0034, respectively). The improvement in FFBF with statin use was independent of ADT use or radiation dose. On multivariable analysis, statin use was associated with improved FFBF (P < .001) along with pretreatment prostate-specific antigen ≤ 8.4 (P < .001), stage less than T2b (P = .0111), and Gleason score < 7 (P = .0098). On univariate analysis, pretreatment total cholesterol < 187 (89% v 80%; P = .0494) and low-density lipoprotein (LDL) < 110 (96% v 85%; P = .0462) were associated with improved 4-year FFBF. Conclusion Statin use was associated with a significant improvement in FFBF, FFADT, and RFS in this cohort of men treated with RT for prostate cancer. The favorable effect of statins may be mediated by direct effect or via the LDL-lowering effect of these medications.

Purpose: Experimental evidence suggests that anticoagulants (ACs) may inhibit cancer growth and metastasis, but clinical data have been limited. We investigated whether use of ACs was associated with the risk of death from prostate cancer. Patients and Methods: This study comprised 5,955 men in the Cancer of the Prostate Strategic Urologic Research Endeavor database with localized adenocarcinoma of the prostate treated with radical prostatectomy (RP) or radiotherapy (RT). Of them, 2,175 (37%) were receiving ACs (warfarin, clopidogrel, enoxaparin, and/or aspirin). The risk of prostate cancer–specific mortality (PCSM) was compared between the AC and non-AC groups. Results: After a median follow-up of 70 months, risk of PCSM was significantly lower in the AC group compared with the non-AC group (3% v 8% at 10 years; P < .01). The risks of disease recurrence and bone metastasis were also significantly lower. In a subgroup analysis by clinical risk category, the reduction in PCSM was most prominent in patients with high-risk disease (4% v 19% at 10 years; P < .01). The benefit from AC was present across treatment modalities (RT or RP). Analysis by type of AC medication suggested that the PCSM reduction was primarily associated with aspirin. Multivariable analysis indicated that aspirin use was independently associated with a lower risk of PCSM (adjusted hazard ratio, 0.43; 95% CI, 0.21 to 0.87; P = .02). Conclusion: AC therapy, particularly aspirin, was associated with a reduced risk of PCSM in men treated with RT or RP for prostate cancer. The association was most prominent in patients with high-risk disease.

BACKGROUND: Substantial experimental evidence suggests that anticoagulants (ACs) may inhibit cancer growth and metastasis, although the limited data from clinical trials have been inconsistent. The potential antineoplastic effect of ACs was investigated in patients who received radiotherapy for localized prostate cancer.METHODS: The study cohort consisted of 662 patients with adenocarcinoma of the prostate who received radiotherapy (RT) with curative intent. Among those 622 men, 243 (37%) were receiving ACs (warfarin, clopidogrel, and/or aspirin). All patients received external‐beam RT, permanent seed implantation, or a combination of both. Prostate‐specific antigen (PSA) values were monitored for biochemical control of disease.RESULTS: At a median follow‐up of 49 months, the biochemical control rate at 4‐years was significantly better in patients who received ACs at 91% compared with 78% in patients who did not receive ACs (P = .0002). The distant metastasis rate at 4 years also was reduced in the AC group compared with the non‐AC group (1% vs 5%; P = .0248). In subgroup analysis, the improvement in biochemical control was significant only for patients with high‐risk disease. Along with Gleason score, T classification, and initial PSA, the use of AC therapy was associated independently with improved biochemical control in multivariate analysis.CONCLUSIONS: AC therapy was associated with an improvement in biochemical control in patients with prostate cancer who received RT with curative intent. The effect was most prominent in patients who had high‐risk disease. Cancer 2010. © 2010 American Cancer Society.

PURPOSE: We sought to investigate whether enzalutamide (ENZA), without concurrent androgen deprivation therapy, increases freedom from prostate-specific antigen (PSA) progression (FFPP) when combined with salvage radiation therapy (SRT) in men with recurrent prostate cancer after radical prostatectomy (RP). PATIENTS AND METHODS: Men with biochemically recurrent prostate cancer after RP were enrolled into a randomized, double‐blind, phase II, placebo-controlled, multicenter study of SRT plus ENZA or placebo (ClinicalTrials.gov identifier: NCT02203695 ). Random assignment (1:1) was stratified by center, surgical margin status (R0 v R1), PSA before salvage treatment (PSA ≥ 0.5 v < 0.5 ng/mL), and pathologic Gleason sum (7 v 8‐10). Patients were assigned to receive either ENZA 160 mg once daily or matching placebo for 6 months. After 2 months of study drug therapy, external-beam radiation (66.6‐70.2 Gy) was administered to the prostate bed (no pelvic nodes). The primary end point was FFPP in the intention-to-treat population. Secondary end points were time to local recurrence within the radiation field, metastasis‐free survival, and safety as determined by frequency and severity of adverse events. RESULTS: Eighty-six (86) patients were randomly assigned, with a median follow-up of 34 (range, 0-52) months. Trial arms were well balanced. The median pre-SRT PSA was 0.3 (range, 0.06-4.6) ng/mL, 56 of 86 patients (65%) had extraprostatic disease (pT3), 39 of 86 (45%) had a Gleason sum of 8-10, and 43 of 86 (50%) had positive surgical margins (R1). FFPP was significantly improved with ENZA versus placebo (hazard ratio [HR], 0.42; 95% CI, 0.19 to 0.92; P = .031), and 2-year FFPP was 84% versus 66%, respectively. Subgroup analyses demonstrated differential benefit of ENZA in men with pT3 (HR, 0.22; 95% CI, 0.07 to 0.69) versus pT2 disease (HR, 1.54; 95% CI, 0.43 to 5.47; P_interaction = .019) and R1 (HR, 0.14; 95% CI, 0.03 to 0.64) versus R0 disease (HR, 1.00; 95% CI, 0.36 to 2.76; P_interaction = .023). There were insufficient secondary end point events for analysis. The most common adverse events were grade 1-2 fatigue (65% ENZA v 53% placebo) and urinary frequency (40% ENZA v 49% placebo). CONCLUSION: SRT plus ENZA monotherapy for 6 months in men with PSA-recurrent high-risk prostate cancer after RP is safe and delays PSA progression relative to SRT alone. The impact of ENZA on distant metastasis or survival is unknown at this time.