Miyazawa Yoshiyuki, Sekine Yoshitaka, Shimizu Nobuaki, Takezawa Yutaka, Nakamura Toshiyuki, Miyao Takeshi, Nakayama Hiroshi, Kurihara Sota, Syuto Takahiro, Nomura Masashi, Koike Hidekazu, Matsui Hiroshi, Shibata Yasuhiro, Suzuki Kazuhiro
Department of Urology, Gunma University Hospital, Japan.
Department of Urology, Gunma Prefectural Cancer Center, Japan.
Prostate. 2019 Sep;79(12):1462-1470. doi: 10.1002/pros.23865. Epub 2019 Jul 23.
Recent studies have shown that an early prostate-specific antigen (PSA) response to androgen receptor-targeting agents in metastatic castration-resistant prostate cancer (mCRPC) is associated with a better prognosis. We analyzed the early PSA response to enzalutamide (ENZ) by measuring the PSA doubling time (PSADT) and PSA velocity (PSAV) while monitoring oncologic outcomes and survival in Japanese patients.
We analyzed a total of 241 patients with mCRPC who were treated with ENZ. The patients' median age was 75 ± 7.9 years (range, 53-93 years). There were 171 (71%) predocetaxel cases, and 70 (29%) post docetaxel cases. PSA-progression-free survival (PFS) and overall survival (OS) were assessed according to Prostate Cancer Working Group 2 criteria. This study was approved by the Institutional Review Board of Gunma University Hospital (No. 1595).
We observed 77 good response (GR; case in which PSA remained low after treatment) cases (31.9%), 125 acquired resistance (AR; decline in PSA after treatment followed by progression) cases (51.9%), and 39 primary resistance (PR; lack of decline in PSA) cases (16.2%). Predocetaxel, PSA-PFS, and OS were significantly higher compared with post docetaxel (PSA-PFS: 47.0 vs 13.4 weeks, P < .001; OS: not yet reached vs 80.7 weeks, P < .001). Multivariate analysis of prognostic factors, including PSA response at 4 weeks, was performed using Cox regression analysis. ECOG PS (0 vs 1-2), hemoglobin (Hb; ≥ 12.2 vs < 12.2 g/dL), time to CRPC ( ≥ 12 vs < 12 m), docetaxel treatment history (no vs yes), and a PSA reduction of 50% at 4 weeks were significant predictors of OS (all, P < .05). In cases of AR (n = 125), multivariate analysis showed that PSA kinetic factors, such as PSADT and PSAV (ng/mL/m), Hb, time to CRPC, PSADT ( ≥ 2 vs < 2 m), and PSAV ( < 20 vs ≥ 20 ng/mL/m), were all predictive of OS following PSA-progression (P < .05).
Our study has demonstrated that PSA dynamics after ENZ administration may be a useful prognostic factor for mCRPC patients.
近期研究表明，转移性去势抵抗性前列腺癌（mCRPC）患者对雄激素受体靶向药物的早期前列腺特异性抗原（PSA）反应与较好的预后相关。我们通过测量PSA倍增时间（PSADT）和PSA速度（PSAV），同时监测日本患者的肿瘤学结局和生存率，分析了恩杂鲁胺（ENZ）的早期PSA反应。
我们分析了总共241例接受ENZ治疗的mCRPC患者。患者的中位年龄为75±7.9岁（范围53 - 93岁）。其中171例（71%）为多西他赛治疗前病例，70例（29%）为多西他赛治疗后病例。根据前列腺癌工作组2标准评估PSA无进展生存期（PFS）和总生存期（OS）。本研究获得群马大学医院机构审查委员会批准（编号1595）。
我们观察到77例良好反应（GR；治疗后PSA持续较低的病例）（31.9%），125例获得性耐药（AR；治疗后PSA下降随后进展）病例（51.9%），以及39例原发性耐药（PR；PSA未下降）病例（16.2%）。多西他赛治疗前的PSA - PFS和OS显著高于多西他赛治疗后（PSA - PFS：47.0对13.4周，P <.001；OS：未达到对80.7周，P <.001）。使用Cox回归分析对包括4周时PSA反应在内的预后因素进行多变量分析。东部肿瘤协作组体能状态（ECOG PS）（0对1 - 2）、血红蛋白（Hb；≥12.2对<12.2 g/dL）、至CRPC的时间（≥12对<12个月）、多西他赛治疗史（无对有）以及4周时PSA降低50%是OS的显著预测因素（均P <.05）。在AR病例（n = 125）中，多变量分析显示，PSADT和PSAV（ng/mL/月）等PSA动力学因素、Hb、至CRPC的时间、PSADT（≥2对<2个月）以及PSAV（<20对≥20 ng/mL/月）均为PSA进展后OS的预测因素（P <.05）。
我们的研究表明，ENZ给药后的PSA动态变化可能是mCRPC患者有用的预后因素。
