Summary There is substantial heterogeneity among primary prostate cancers, evident in the spectrum of molecular abnormalities and its variable clinical course. As part of The Cancer Genome Atlas (TCGA), we present a comprehensive molecular analysis of 333 primary prostate carcinomas. Our results revealed a molecular taxonomy in which 74% of these tumors fell into one of seven subtypes defined by specific gene fusions (ERG, ETV1/4, FLI1) or mutations (SPOP, FOXA1, IDH1). Epigenetic profiles showed substantial heterogeneity, including an IDH1-mutant subset with a methylator phenotype. Androgen receptor (AR) activity varied widely and in a subtype-specific manner with SPOP and FOXA1 mutant tumors having the highest levels of AR-induced transcripts. 25% of the prostate cancers had a presumed actionable lesion in the PI3K or MAPK signaling pathways, and DNA repair genes were inactivated in 19%. Our analysis reveals molecular heterogeneity among primary prostate cancers, as well as potentially actionable molecular defects.

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A growing literature supports the safety and efficacy of active surveillance for patients with low-risk prostate cancer. However, the experience behind this literature is based almost entirely in academic centers, and prior reports have consistently found surveillance generally underused in most other settings. 1,2 Conversely, high-risk tumors have been undertreated with androgen deprivation treatment alone. 2,3 Recent trends in community-based practice patterns have not been well documented.Methods | Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) is a national registry accruing men with prostate cancer diagnosed at 45 urology practices across the United States since 1995. A mix of large and small practices are included. All but 3 are community-based practices and 28 states across all regions are represented. Both prospective enrollment of newly diagnosed men and retrospective enrollment of previously diagnosed men were permitted before 1998; however, since 1998 all enrollment has been prospective.