Department of Radiation Oncology; Harold C. Simmons Comprehensive Cancer Center; University of Texas at Southwestern Medical Center; Dallas, TX USA.
Department of Clinical Sciences; Harold C. Simmons Comprehensive Cancer Center; University of Texas at Southwestern Medical Center; Dallas, TX USA.
Cancer Biol Ther. 2014 Jun 1;15(6):699-706. doi: 10.4161/cbt.28554. Epub 2014 Mar 21.
High-risk prostate cancer (PC) has poor outcomes due to therapeutic resistance to conventional treatments, which include prostatectomy, radiation, and hormone therapy. Previous studies suggest that anticoagulant (AC) use may improve treatment outcomes in PC patients. We hypothesized that AC therapy confers a freedom from biochemical failure (FFBF) and overall survival (OS) benefit when administered with radiotherapy in patients with high-risk PC.
Analysis was performed on 74 high-risk PC patients who were treated with radiotherapy from 2005 to 2008 at UT Southwestern. Of these patients, 43 were on AC including aspirin (95.6%), clopidogrel (17.8%), warfarin (20%), and multiple ACs (31.1%). Associations between AC use and FFBF, OS, distant metastasis, and toxicity were analyzed.
Median follow-up was 56.6 mo for all patients. For patients taking any AC compared with no AC, there was improved FFBF at 5 years of 80% vs. 62% (P = 0.003), and for aspirin the FFBF was 84% vs. 65% (P = 0.008). Aspirin use was also associated with reduced rates of distant metastases at 5 years (12.2% vs. 26.7%, P = 0.039). On subset analysis of patients with Gleason score (GS) 9-10 histology, aspirin resulted in improved 5-year OS (88% vs. 37%, P = 0.032), which remained significant on multivariable analysis (P<0.05).
AC use was associated with a FFBF benefit in high-risk PC which translated into an OS benefit in the highest risk PC patients with GS 9-10, who are most likely to experience mortality from PC. This hypothesis-generating result suggests AC use may represent an opportunity to augment current therapy.
由于对传统治疗方法（包括前列腺切除术、放疗和激素治疗）存在治疗抵抗，高危前列腺癌（PC）患者的预后较差。先前的研究表明，抗凝（AC）治疗可能会改善 PC 患者的治疗结果。我们假设，在高危 PC 患者中，AC 治疗与放疗联合应用可带来生化无失败（FFBF）和总生存（OS）获益。
对 2005 年至 2008 年在 UT 西南接受放疗的 74 例高危 PC 患者进行了分析。这些患者中，43 例正在接受 AC 治疗，包括阿司匹林（95.6%）、氯吡格雷（17.8%）、华法林（20%）和多种 AC 联合治疗（31.1%）。分析了 AC 使用与 FFBF、OS、远处转移和毒性之间的相关性。
所有患者的中位随访时间为 56.6 个月。与未使用 AC 的患者相比，使用任何 AC 的患者在 5 年时的 FFBF 更高，分别为 80%和 62%（P = 0.003），而阿司匹林的 FFBF 为 84%和 65%（P = 0.008）。阿司匹林的使用也与 5 年内远处转移发生率降低相关（12.2%和 26.7%，P = 0.039）。在 GS 9-10 组织学的患者亚组分析中，阿司匹林可改善 5 年 OS（88%和 37%，P = 0.032），在多变量分析中仍然具有统计学意义（P<0.05）。
AC 治疗与高危 PC 的 FFBF 获益相关，这在 GS 9-10 最高危 PC 患者中转化为 OS 获益，这些患者最有可能因 PC 而死亡。这一产生假说的结果表明，AC 治疗可能代表了增强当前治疗的机会。
