Biomarker Approaches to Individualizing Systemic Therapy for High Risk Prostate Cancer

项目摘要 尽管前列腺癌（PCa）男性疾病管理的风险分层工具取得了进展， 仍然缺乏旨在识别非洲裔美国人（AAM）风险增加的预后工具。 在放射治疗（RT）和雄激素剥夺激素治疗（ADT）的情况下的致死性前列腺癌。 预后生物标志物面板，如Decipher，已在手术队列中开发和验证， 尚未系统验证RT + ADT后的预后性能。此外，使用的队列 推导和验证这些预测工具，总的来说，是由欧洲后裔组成的， 患者这限制了非洲裔患者的预后能力，这些患者已被证明具有 基于临床病理因素（包括前列腺特异性抗原）的前列腺癌特异性结局更差 (PSA)Gleason评分和肿瘤分期。没有从种族平等透镜的角度开发预测工具， 种族和血统的作用在治疗建议指南中只是一个事后的想法， 源自欧洲中心的临床研究。到目前为止，种族问题一直处于边缘地位， 以临床上有意义的方式对识别、预后、治疗建议和成本做出贡献- 对非洲裔男子的有效性分析。这限制了我们识别非白人男性的能力， 致命PCa的风险增加，使治疗强化不那么精确，限制了更多治疗的有效性。 密集的治疗干预，并导致现有差距扩大。为了解决缺乏 常规使用分子生物标志物在接受以下治疗的高危PCa男性中进行治疗决策 最终RT，父母补助金建议"开发和验证临床有用和具有成本效益的预后 和预测性生物标志物。"这一补充旨在扩大 父母补助金，通过利用健康公平原则，将调查结果的范围扩大到传统的 以欧洲为中心的人群，这样做提高了R01结果的普遍性，以包括AAM。这将 （1）比较最佳预后标志的临床表现和随后的预后标志的临床表现。 最好的预后工具，来自基因组和临床病理数据的整合，来自父母的资助目的 1，AAM和接受RT治疗的患有PCa的白色男性（WM）之间，以及（2）确定是否基于生物标志物 分配到短期ADT（施塔特）与长期ADT（LTADT）与LTADT+强化，具有成本效益 AAM与WM与高风险PCa相比，来自父母资助目标3。成功完成此补充 将扩大父R01赠款的调查结果，以专门关注AAM。扩大调查结果的范围 超越了传统的欧洲中心人口。

PROJECT SUMMARY Despite the advancement of risk stratification tools on disease management for men with prostate cancer (PCa), there is still a paucity of prognostic tools aimed at identifying African American men (AAM) at increased risk for lethal prostate cancer in the setting of radiation therapy (RT) and androgen deprivation hormone therapy (ADT). Prognostic biomarker panels, such as Decipher, which have been developed and validated in surgical cohorts, have not been systematically validated for prognostic performance after RT+ADT. Furthermore, the cohorts used to derive and validate these prognostic tools have been, on the whole, made up of European-descendent patients. This has limited the prognostic ability in patients of African-descent, who have been shown to have worse prostate cancer-specific outcomes based on clinicopathologic factors including prostate-specific antigen (PSA), Gleason score, and tumor stage. Prognostic tools have not been developed with a racial equity lens, and the role of race and ancestry have only been an afterthought in the treatment recommendation guidelines resulting from Eurocentrically derived clinical studies. As of yet, race has remained on the sidelines without contributing in a clinically meaningful way to the identification, prognosis, treatment recommendations, and cost- effectiveness analysis for men of African-descent. This has limited our ability to identify non-white men at increased risk for lethal PCa, making treatment intensification less precise, limiting the effectiveness of more intense treatment interventions, and contributing to the widening of existing disparities. To address the lack of routine use of molecular biomarkers for therapeutic decision making in men with high-risk PCa, treated with definitive RT, the parent grant proposes to “develop and validate clinically useful and cost-effective prognostic and predictive biomarkers for high-risk PCa patients treated with RT.” This supplement seeks to expand the parent grant, by utilizing principles of health equity, to extend the reach of the findings beyond the traditional Eurocentric population, and in doing so improve the generalizability of the R01 findings to include AAM. This will be accomplished by: (1) comparing the clinical performance of the best prognostic signature and subsequent best prognostic tool, derived from integration of the genomic and clinicopathologic data, from parent grant Aim 1, between AAM and White men (WM) with PCa treated with RT, and (2) determine whether biomarker-based assignment to short-term ADT (STADT) vs. long-term ADT (LTADT) vs. LTADT+intensification, is cost-effective in AAM compared to WM with high-risk PCa, from parent grant Aim 3. Successful completion of this supplement will expand the findings of the parent R01 grant to focus specifically at AAM. Extending the reach of the findings beyond the traditional Eurocentric population.