Henry Ford Health, Detroit, Michigan.
University of Michigan, Ann Arbor, Michigan.
JAMA Netw Open. 2023 Sep 5;6(9):e2334208. doi: 10.1001/jamanetworkopen.2023.34208.
Black men have higher incidence and mortality from prostate cancer. Whether precision oncology disparities affect Black men with metastatic castration-resistant prostate cancer (mCRPC) is unknown.
To compare precision medicine data and outcomes between Black and White men with mCRPC.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used data collected by the Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort (PROMISE) consortium, a multi-institutional registry with linked clinicogenomic data, from April 2020 to December 2021. Participants included Black and White patients with mCRPC with molecular data. Data were analyzed from December 2021 to May 2023.
Database-reported race and ethnicity.
The primary outcome was the frequency of actionable molecular data, defined as the presence of mismatch repair deficiency (MMRD) or high microsatellite instability (MSI-H), homologous recombination repair deficiency, or tumor mutational burden of 10 mutations per megabase or greater. Secondary outcomes included the frequency of other alterations, the type and timing of genomic testing performed, and use of targeted therapy. Efficacy outcomes were prostate-specific antigen response rate, site-reported radiographic response, and overall survival.
A total of 962 eligible patients with mCRPC were identified, including 204 Black patients (21.2%; median [IQR] age at diagnosis, 61 [55-67] years; 131 patients [64.2%] with Gleason scores 8-10; 92 patients [45.1%] with de novo metastatic disease) and 758 White patients (78.8%; median [IQR] age, 63 [57-69] years; 445 patients [58.7%] with Gleason scores 8-10; 310 patients [40.9%] with de novo metastatic disease). Median (IQR) follow-up from mCRPC was 26.6 (14.2-44.7) months. Blood-based molecular testing was more common in Black men (111 men [48.7%]) than White men (317 men [36.4%]; P < .001). Rates of actionable alterations were similar between groups (65 Black men [32.8%]; 215 White men [29.1%]; P = .35), but MMRD or MSI-H was more common in Black men (18 men [9.1]) than White men (36 men [4.9%]; P = .04). PTEN alterations were less frequent in Black men than White men (31 men [15.7%] vs 194 men [26.3%]; P = .003), as were TMPRSS alterations (14 men [7.1%] vs 155 men [21.0%]; P < .001). No other differences were seen in the 15 most frequently altered genes, including TP53, AR, CDK12, RB1, and PIK3CA. Matched targeted therapy was given less frequently in Black men than White men (22 men [33.5%] vs 115 men [53.5%]; P = .008). There were no differences in response to targeted therapy or survival between the two cohorts.
This cohort study of men with mCRPC found higher frequency of MMRD or MSI-H and lower frequency of PTEN and TMPRSS alterations in Black men compared with White men. Although Black men received targeted therapy less frequently than White men, no differences were observed in clinical outcomes.
黑人男性患有前列腺癌的发病率和死亡率更高。精准肿瘤学的差异是否会影响转移性去势抵抗性前列腺癌（mCRPC）的黑人男性尚不清楚。
比较黑人男性和白人男性 mCRPC 患者的精准医学数据和结果。
设计、地点和参与者：这项回顾性队列研究使用了前列腺癌精准医学多机构合作努力（PROMISE）联盟收集的数据，该联盟是一个具有连锁临床基因组数据的多机构注册处，从 2020 年 4 月至 2021 年 12 月。参与者包括患有 mCRPC 且具有分子数据的黑人男性和白人男性。数据分析于 2023 年 12 月至 5 月进行。
数据库报告的种族和民族。
主要结果是可操作的分子数据的频率，定义为错配修复缺陷（MMRD）或高微卫星不稳定性（MSI-H）、同源重组修复缺陷或肿瘤突变负担为每兆碱基 10 个突变或更高的存在。次要结果包括其他改变的频率、进行的基因组检测的类型和时间，以及靶向治疗的使用。疗效结果是前列腺特异性抗原反应率、部位报告的放射学反应率和总生存率。
共确定了 962 名符合条件的 mCRPC 患者，包括 204 名黑人患者（21.2%；诊断时的中位[IQR]年龄为 61[55-67]岁；131 名患者[64.2%]的 Gleason 评分为 8-10；92 名患者[45.1%]为初发性转移性疾病）和 758 名白人患者（78.8%；中位[IQR]年龄为 63[57-69]岁；445 名患者[58.7%]的 Gleason 评分为 8-10；310 名患者[40.9%]为初发性转移性疾病）。从 mCRPC 开始的中位（IQR）随访时间为 26.6（14.2-44.7）个月。黑人男性的血液分子检测更为常见（111 名男性[48.7%]），而白人男性（317 名男性[36.4%]；P<.001）则较少。两组的可操作改变率相似（65 名黑人男性[32.8%]；215 名白人男性[29.1%]；P=0.35），但黑人男性 MMRD 或 MSI-H 更为常见（18 名男性[9.1%]），而白人男性则较少（36 名男性[4.9%]；P=0.04）。PTEN 改变在黑人男性中比在白人男性中更少见（31 名男性[15.7%]与 194 名男性[26.3%]；P=0.003），TMPRSS 改变也是如此（14 名男性[7.1%]与 155 名男性[21.0%]；P<.001）。在最常改变的 15 个基因中，包括 TP53、AR、CDK12、RB1 和 PIK3CA，没有发现其他差异。与白人男性相比，黑人男性给予的匹配靶向治疗较少（22 名男性[33.5%]与 115 名男性[53.5%]；P=0.008）。两组患者在靶向治疗反应或生存方面没有差异。
这项对 mCRPC 男性的队列研究发现，与白人男性相比，黑人男性的 MMRD 或 MSI-H 频率更高，PTEN 和 TMPRSS 改变频率更低。尽管黑人男性接受靶向治疗的频率低于白人男性，但在临床结果方面没有观察到差异。
