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Abstract：
BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease with prognoses varying from months to years at time of castration-resistant diagnosis. Optimal first-line therapy for those with different prognoses is unknown.
METHODS: We conducted a retrospective cohort study of men in a national healthcare delivery system receiving first-line therapy for mCRPC (abiraterone, enzalutamide, docetaxel, or ketoconazole) from 2010 to 2017, with follow-up through 2019. Using commonly drawn prognostic labs at start of mCRPC therapy (hemoglobin, albumin, and alkaline phosphatase), we categorized men into favorable, intermediate, or poor prognostic groups depending on whether they had none, one to two, or all three laboratory values worse than designated laboratory cutoffs. We used Kaplan-Meier methods to examine prostate specific antigen (PSA) progression-free and overall survival (OS) according to prognostic group and first-line therapy, and multivariable cox regression to determine variables associated with survival outcomes.
RESULTS: Among 4135 patients, median PSA progression-free survival (PFS) was 6.9 months (95% confidence interval [CI] 6.6-7.3), and median OS 18.8 months (95% CI 18.0-19.6), ranging from 5.7 months (95% CI 4.8-7.0) in the poor prognosis group to 31.3 months (95% CI 29.7-32.9) in the favorable group. OS was similar regardless of initial treatment received for favorable and intermediate groups, but worse for those in the poor prognostic group who received ketoconazole (adjusted hazard ratio 2.07, 95% CI 1.2-3.6). PSA PFS was worse for those who received ketoconazole compared to abiraterone across all prognostic groups (favorable HR 1.76, 95% CI 1.34-2.31; intermediate HR 1.78, 95% CI 1.41-2.25; poor HR 8.01, 95% CI 2.93-21.9).
CONCLUSIONS: Commonly drawn labs at mCRPC treatment start may aid in predicting survival and response to therapies, potentially informing discussions with care teams. First-line treatment selection impacts disease progression for all men with mCRPC regardless of prognostic group, but impacted OS only for men with poor prognosis at treatment start.
METHODS: We conducted a retrospective cohort study of men in a national healthcare delivery system receiving first-line therapy for mCRPC (abiraterone, enzalutamide, docetaxel, or ketoconazole) from 2010 to 2017, with follow-up through 2019. Using commonly drawn prognostic labs at start of mCRPC therapy (hemoglobin, albumin, and alkaline phosphatase), we categorized men into favorable, intermediate, or poor prognostic groups depending on whether they had none, one to two, or all three laboratory values worse than designated laboratory cutoffs. We used Kaplan-Meier methods to examine prostate specific antigen (PSA) progression-free and overall survival (OS) according to prognostic group and first-line therapy, and multivariable cox regression to determine variables associated with survival outcomes.
RESULTS: Among 4135 patients, median PSA progression-free survival (PFS) was 6.9 months (95% confidence interval [CI] 6.6-7.3), and median OS 18.8 months (95% CI 18.0-19.6), ranging from 5.7 months (95% CI 4.8-7.0) in the poor prognosis group to 31.3 months (95% CI 29.7-32.9) in the favorable group. OS was similar regardless of initial treatment received for favorable and intermediate groups, but worse for those in the poor prognostic group who received ketoconazole (adjusted hazard ratio 2.07, 95% CI 1.2-3.6). PSA PFS was worse for those who received ketoconazole compared to abiraterone across all prognostic groups (favorable HR 1.76, 95% CI 1.34-2.31; intermediate HR 1.78, 95% CI 1.41-2.25; poor HR 8.01, 95% CI 2.93-21.9).
CONCLUSIONS: Commonly drawn labs at mCRPC treatment start may aid in predicting survival and response to therapies, potentially informing discussions with care teams. First-line treatment selection impacts disease progression for all men with mCRPC regardless of prognostic group, but impacted OS only for men with poor prognosis at treatment start.
摘要：
背景：转移性去势抵抗性前列腺癌（mCRPC）是一种异质性疾病，在去势抵抗性诊断时，预后从数月到数年不等。对于预后不同的患者，最佳的一线治疗是未知的。
方法：我们对接受mCRPC一线治疗的国家医疗保健提供系统中的男性进行了回顾性队列研究（阿比特龙，恩扎鲁他胺,多西他赛,或酮康唑）从2010年到2017年，随访到2019年。在mCRPC治疗开始时使用通常绘制的预后实验室(血红蛋白，白蛋白,和碱性磷酸酶)，我们把男人分为有利的，中间,或者预后不良的组，取决于他们是否没有，一到二，或所有三个实验室值均比指定的实验室截止值差。我们使用Kaplan-Meier方法根据预后组和一线治疗方法检查前列腺特异性抗原（PSA）无进展和总生存期（OS）。和多变量cox回归来确定与生存结果相关的变量。
结果：在4135名患者中，中位PSA无进展生存期（PFS）为6.9个月（95%置信区间[CI]6.6-7.3），和中位OS18.8个月（95%CI18.0-19.6），预后不良组的5.7个月（95％CI4.8-7.0）至预后良好组的31.3个月（95％CI29.7-32.9）。OS是相似的，无论接受的初始治疗有利和中间组，但预后不良组接受酮康唑治疗的患者情况更糟(校正后风险比2.07,95%CI1.2-3.6).在所有预后组中，与阿比特龙相比，接受酮康唑治疗的患者的PSAPFS较差（良好的HR1.76，95％CI1.34-2.31；中等HR1.78，95％CI1.41-2.25；较差的HR8.01，95％CI2.93-21.9）。
结论：在mCRPC治疗开始时常用的实验室可能有助于预测生存率和对治疗的反应，可能会告知与护理团队的讨论。一线治疗选择会影响所有mCRPC患者的疾病进展，而与预后组无关。但影响OS仅在治疗开始时预后不良的男性。
方法：我们对接受mCRPC一线治疗的国家医疗保健提供系统中的男性进行了回顾性队列研究（阿比特龙，恩扎鲁他胺,多西他赛,或酮康唑）从2010年到2017年，随访到2019年。在mCRPC治疗开始时使用通常绘制的预后实验室(血红蛋白，白蛋白,和碱性磷酸酶)，我们把男人分为有利的，中间,或者预后不良的组，取决于他们是否没有，一到二，或所有三个实验室值均比指定的实验室截止值差。我们使用Kaplan-Meier方法根据预后组和一线治疗方法检查前列腺特异性抗原（PSA）无进展和总生存期（OS）。和多变量cox回归来确定与生存结果相关的变量。
结果：在4135名患者中，中位PSA无进展生存期（PFS）为6.9个月（95%置信区间[CI]6.6-7.3），和中位OS18.8个月（95%CI18.0-19.6），预后不良组的5.7个月（95％CI4.8-7.0）至预后良好组的31.3个月（95％CI29.7-32.9）。OS是相似的，无论接受的初始治疗有利和中间组，但预后不良组接受酮康唑治疗的患者情况更糟(校正后风险比2.07,95%CI1.2-3.6).在所有预后组中，与阿比特龙相比，接受酮康唑治疗的患者的PSAPFS较差（良好的HR1.76，95％CI1.34-2.31；中等HR1.78，95％CI1.41-2.25；较差的HR8.01，95％CI2.93-21.9）。
结论：在mCRPC治疗开始时常用的实验室可能有助于预测生存率和对治疗的反应，可能会告知与护理团队的讨论。一线治疗选择会影响所有mCRPC患者的疾病进展，而与预后组无关。但影响OS仅在治疗开始时预后不良的男性。
