Evaluating the clinical, environmental, genetic, and genomic profile of men with early-onset aggressive prostate cancer (PCa).

Abstract

Listen

Translate article

TPS333 Background: Although PCa incidence has stabilized or decreased in most age groups, the incidence of metastatic disease has increased among men 50-69 years old. The incidence of fatal PCa has decreased for most age groups, it has remained unchanged in men under 55 years old. These observations are supported by data from 3 randomized trials. In S9346 in newly diagnosed M1, 18% of men (all-comers N = 3040) were ≤ 60 years. A significant percentage of younger men enrolled in CHAARTED had de-novo metastases at diagnosis; among 575 patients without prior local therapy, the median age was 62 years, and among men < 60 years old (n = 274), 80.3% (n = 220) had de novo metastatic disease. Lastly, in S9921 (N = 983) 15% of men ≤ 60 years had pN1 disease at enrollment. A significant proportion of men with metastatic disease progress to castration -resistance within a short interval of initiating androgen-deprivation therapy (ADT) ± docetaxel or abiraterone for metastatic hormone sensitive PCa. Pivotal studies have described genetic abnormalities in aggressive localized or end stage prostate cancers, but early-onset cases and those with early progression on systemic therapy are not included or are under-represented in these studies. Methods: The primary objective of this multi-institutional trial is to characterize the clinical, environmental, genetic and genomic features of high-risk advanced PCa: Cohort 1: men ≤ 60 years old with N1 or M1 at diagnosis or who develop metastases shortly after local therapy; Cohort 2: men with early progression to castration-resistant PCa in ≤ 1 year on ADT ± docetaxel or ADT ± abiraterone. Clinical and environmental history, peripheral blood for cell free DNA and germline analysis will be collected. Primary/metastatic tumor tissue will be tested via the Tempus platform, which includes DNA sequencing, whole transcriptome expression profiling, copy number analysis, comprehensive fusion gene analysis and calculation of tumor mutational burden. We will also prospectively correlate clinical and molecular characteristics with outcomes. To date, 5 patients have been registered.