Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
VA Health Services Research & Development, Center for Clinical Management and Research, VA Ann Arbor Healthcare System, Ann Arbor, Michigan, USA.
Cancer Med. 2024 Jun;13(12):e7334. doi: 10.1002/cam4.7334.
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.
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.
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).
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.
转移性去势抵抗性前列腺癌（mCRPC）是一种异质性疾病，从去势抵抗诊断时的数月到数年不等。对于预后不同的患者，最佳的一线治疗方法尚不清楚。
我们对 2010 年至 2017 年间在国家医疗保健系统中接受一线 mCRPC 治疗（阿比特龙、恩杂鲁胺、多西他赛或酮康唑）的男性进行了回顾性队列研究，并随访至 2019 年。根据开始 mCRPC 治疗时常用的预后实验室检查（血红蛋白、白蛋白和碱性磷酸酶），我们将男性分为预后良好、中等或较差的组，具体取决于他们是否有任何一种、一种或两种或三种实验室值低于指定的实验室截止值。我们使用 Kaplan-Meier 方法根据预后组和一线治疗观察前列腺特异性抗原（PSA）无进展生存期（PFS）和总生存期（OS），并使用多变量 Cox 回归确定与生存结果相关的变量。
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），中位 OS 为 18.8 个月（95%CI18.0-19.6），从预后较差组的 5.7 个月（95%CI4.8-7.0）到预后良好组的 31.3 个月（95%CI29.7-32.9）不等。对于预后良好和中等组的患者，无论接受何种初始治疗，OS 均相似，但对于预后较差组接受酮康唑治疗的患者（调整后的危险比 2.07，95%CI1.2-3.6），OS 更差。与阿比特龙相比，在所有预后组中，接受酮康唑治疗的患者 PSA PFS 更差（预后良好 HR 1.76，95%CI1.34-2.31；中等 HR 1.78，95%CI1.41-2.25；差 HR 8.01，95%CI2.93-21.9）。
mCRPC 治疗开始时常用的实验室检查结果可能有助于预测生存和对治疗的反应，这可能有助于与护理团队进行讨论。一线治疗选择会影响所有 mCRPC 患者的疾病进展，而无论预后组如何，但仅影响治疗开始时预后较差的患者的 OS。
