Defining the Biological Arc of Grade Group 1 Prostate Cancer

该项目的长期目标是进一步减少与监测有关的生物不确定性， 前列腺癌的风险很大虽然大多数患有可诊断疾病的男性都是监测的候选人， 它的使用情况差别很大，在各个提供者之间从20%到90%不等。执行的主要障碍 由供应商，并接受患者，涉及到周围的生物学的不确定性1级组（GG 1; 格里森前列腺癌。尚未解决的关键问题包括：GG 1前列腺癌是否会随着时间的推移而进展？ GG 1癌是否与高级别疾病和淋巴结转移共享分子起源？有 GG 1肿瘤的分子特征，预测存在同步的，但未检测到的，更高级别的 前列腺其他部位的疾病GG 1癌症在非洲裔美国人中更具侵袭性吗？当然， GG 1前列腺癌的生物学轨迹代表了一个关键的知识缺口。我们假设GG 1 前列腺癌很少经历克隆级进展，并且GG 1癌症中的分子变化不 预测同步高级别疾病的存在。为了验证这些假设，我们提出以下建议： 目的：1）确定男性中的高级别前列腺癌是否由GG 1前列腺癌克隆性产生 随着时间的推移进行监测，2）在分子水平上解剖GG 1前列腺癌， 同步分级不一致的多灶性，和3）询问原发性多灶性前列腺癌的共享 GG 1与较高级别疾病/淋巴结或远处转移之间的克隆性。成功 该项目目标的完成将改变GG 1前列腺癌患者的临床管理方式 通过进一步减少关于可诊断风险疾病的临床和分子弧的不确定性。实际上，这些 这些发现有可能在选择GG 1监测时为提供者和患者提供信心 通过减少对克隆性疾病进展的担忧， 共存的高风险癌症，尚未被发现的因素，发挥关键作用的选择和 有效实施监督。我们的研究团队由前列腺癌专家组成 管理，分子分析和生物信息学，再加上我们独特的和广泛的访问， 相关的组织资源，是唯一准备完成我们的研究计划。 PHS 398/2590（Rev.6/09）

The long-term goal of this project is to further reduce the biological uncertainty associated with surveillance for favorable-risk prostate cancer. Although most men with favorable-risk disease are candidates for surveillance, its use varies widely and ranges from 20 to 90% across individual providers. A major barrier to implementation by providers, and acceptance by patients, relates to uncertainty around the biology of Grade Group 1 (GG1; Gleason 6) prostate cancer. Key unresolved questions include: Does GG1 prostate cancer progress over time? Does GG1 cancer share molecular origins with higher-grade disease and lymph node metastases? Are there molecular features of GG1 tumors that predict the presence of synchronous, but undetected, higher-grade disease elsewhere in the prostate? Is GG1 cancer more aggressive in African Americans? To be sure, the biological trajectory of GG1 prostate cancer represents a critical knowledge gap. We hypothesize that GG1 prostate cancer rarely undergoes clonal grade progression, and that molecular changes in GG1 cancer do not predict the presence of synchronous higher-grade disease. To test these hypotheses, we propose the following aims: 1) to determine if high-grade prostate cancer arises clonally from GG1 prostate cancer in men on surveillance over time, 2) to molecularly dissect GG1 prostate cancer both within and without the context of synchronous grade discordant multifocality, and 3) to interrogate primary multifocal prostate cancer for shared clonality between GG1 and higher-grade disease/lymph node or distant metastases. The successful completion of the aims of this project will alter the way men with GG1 prostate cancer are clinically managed by further reducing uncertainty about the clinical and molecular arc of favorable-risk disease. Practically, these findings have the potential to provide confidence to providers and patients when selecting surveillance for GG1 prostate cancer by reducing concerns over clonal disease progression and by shedding light on the likelihood of co-existing higher-risk cancer that has yet to be detected—factors that play key roles in the selection and effective implementation of surveillance. Our research team composed of experts in prostate cancer management, molecular profiling, and bioinformatics, coupled with our distinctive and extensive access to relevant tissue resources, is uniquely poised to complete our research plan. PHS 398/2590 (Rev. 6/09) Page Continuation Format Page