Anticoagulant Use is Associated with Improved Biochemical Control of High-Risk Prostate Cancer Patients Treated with Radiation Therapy

INTRODUCTION: The coagulation system modulates multiple cancer pathways, including tumor proliferation, angiogenesis, host immunologic defense, and metastasis. Prior studies have reported improved survival and freedom from biochemical failure (FFBF) in prostate cancer (PCa) patients taking aspirin and other anticoagulants (ACs). We reviewed the outcomes of patients with high-risk PCa who received ACs and definitive radiation therapy (RT). METHODS: Patients with nonmetastatic high-risk adenocarinoma of the prostate (stage ≥ T3a, or Gleason score (GS) ≥ 8, or prostate-specific antigen (PSA) ≥ 20) treated with definitive RT between 2005-2008 at UTSW were identified. The AC group consisted of patients who had warfarin, clopidogrel, or aspirin recorded on the medication list at any clinical visit. FFBF of patients was determined using the Phoenix definition. Log-rank test was used to correlate FFBF with the ACs. Univariate and multivariate analysis (MVA) of FFBF to pretreatment PSA, GS, stage, hormone use, total RT dose, and ACs was performed. RESULTS: Among the 76 patients identified, 45 (59.2%) comprised the AC group. Within the AC group, 43 were taking aspirin, 8 were taking warfarin, 8 were taking clopidogrel, and 13 were taking multiple ACs. Median follow up was 61.2 months (range 3.1-89.4) for the AC group and 55.1 months (range 6.5-88.9) for the non-AC group. Patients receiving ACs exhibited significantly improved FFBF compared to the control group (p=0.0018; log-rank test). The estimated 4-year FFBF was 83.7% and 63.2% for the AC and non-AC groups, respectively. Among the patients taking a single AC, only aspirin showed significantly improved FFBF (p=0.0037). The hazard ratio for T-stage was 1.18 (95% CI 0.75, 1.85; p=0.4672) in the AC group and 1.67 (95% CI 1.09, 2.58; p=0.0196) in the non-AC group, implying a benefit from taking the AC. Aspirin use, T-stage, and N-stage remained significantly correlated to FFBF (p=0.0002, p=0.0056, and p=0.0040, respectively). The early and late grade 2 toxicity rates for rectal bleeding were 7.7% in patients on multiple ACs and 0% for patients on a single AC or no AC. No patients experienced grade 3 rectal toxicity. CONCLUSION: Use of ACs in high-risk PCa patients improved the FFBF after definitive RT without increasing rates of rectal bleeding. This suggests that daily use of a single anticoagulant, especially aspirin, in high-risk PCa patients treated with definitive RT decreases biochemical failure and may improve outcome. Large prospective data are needed to validate the findings of this study.