Prognostic factors for clinical outcomes in patients with metastatic castration resistant prostate cancer treated with sequential novel androgen receptor-directed therapies
Prognostic factors for clinical outcomes in patients with metastatic castration resistant prostate cancer treated with sequential novel androgen receptor-directed therapies
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DOI：
10.1002/pros.23141
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发表时间：
2016-04-01
期刊：
影响因子：
2.8
通讯作者：
Eisenberger, Mario A.
中科院分区：
文献类型：
--
作者：
Nadal, Rosa;Tsai, Hua-Ling;Eisenberger, Mario A.
与转移性去势抵抗性前列腺癌（mCRPC）患者的临床结局相关的预后因素与一种新的雄激素受体导向疗法（ARDT）在二线setting.Patients和METHODS尚未正式评估我们回顾性审查和分析的所有mCRPC患者的病历接受序贯治疗与ARDT。我们分析了与治疗后终点相关的潜在临床因素，包括前列腺特异性抗原（PSA）下降50%、PSA无进展生存期（PFS）、临床或放射学PFS和总生存期（OS）。预后单变量和多变量考克斯比例风险模型被开发和评估。纳入126例接受二线新型ARDT治疗的mCRPC患者。总体而言，在22%的患者中观察到PSA下降50%，中位PSA-PFS为2.9个月，PFS为3.6个月。调整潜在混杂因素（包括既往多西他赛暴露和既往抗雄激素药物数量）后，至发生CRPC的时间是与PSA-PFS（风险比[HR]：0. 99; 95%置信区间[CI]：0. 99 -1; P= 0. 02）和PFS（HR：0. 99; CI：0. 98 -1; P= 0. 01）相关的独立因素。一线新型ARDT的PSA缓解（下降50%）与二线新型ARDT的PSA-PFS呈负相关（HR：1.7; 95% CI：1.14-2.53; P=0.009），治疗前白蛋白水平较低与PFS较短相关（HR：0.56; 95% CI：0.32-0.97; P=0.03）。体力状态，治疗前白蛋白水平，疾病程度和时间发展CRPC与OS.CONCLUSIONSSecond-line ARDT与中度结局mCRPC患者。至发生CRPC的时间是PSA缓解、PSA-PFS和OS的最强预测因子，这表明对AR定向治疗的内在耐药性是这些患者的主要治疗结局因素。未来在接受长期ARTD治疗的患者中进行的研究应包括识别预测性生物标志物，以促进治疗选择。前列腺76：512-520，2016年。(c)2015 Wiley Periodicals，Inc.
BACKGROUNDPrognostic factors associated with clinical outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with a novel androgen receptor-directed therapies (ARDT) in the second line setting has not been formally evaluated.PATIENTS AND METHODSWe retrospectively reviewed and analyzed medical records of all patients with mCRPC who received sequential treatment with ARDT. We analyzed potential clinical factors associated with post treatment endpoints including 50% decline in prostatic-specific antigen (PSA), PSA-progression-free survival (PFS), clinical or radiographic PFS and overall survival (OS). Prognostic univariate and multivariate Cox proportional hazard models were developed and assessed.RESULTSOne hundred twenty-six patients with mCRPC treated with a second-line novel ARDT were included. Overall, 50% decline in PSA was observed in 22% of patients and a median PSA-PFS of 2.9 months and a PFS of 3.6 months. After adjusting for potential confounders including prior exposure to docetaxel and number of prior antiandrogen agents, time to development of CRPC was an independent factor associated with PSA-PFS (hazard ratio [HR]: 0.99; 95% confidence interval [CI]: 0.99-1; P=0.02) and PFS (HR: 0.99; CI: 0.98-1; P=0.01). PSA response (50% decline) to first-line novel ARDT correlated negatively with PSA-PFS with second-line novel ARDT (HR: 1.7; 95% CI: 1.14-2.53; P=0.009) and lower pre-treatment levels of albumin were associated with shorter PFS (HR: 0.56; 95% CI: 0.32-0.97; P=0.03). Performance status, pre-treatment levels of albumin, extent of disease and time to development CRPC were associated with OS.CONCLUSIONSSecond-line ARDT is associated with modest outcomes in patients with mCRPC. Time to development of CRPC is the strongest predictor of PSA response, PSA-PFS and OS which suggest that intrinsic resistance to AR directed treatment is the major treatment outcome factor in these patients. Future studies in patients receiving long term ARTD should include the identification of predictive biomarkers to facilitate treatment selection. Prostate 76:512-520, 2016. (c) 2015 Wiley Periodicals, Inc.