Integrative molecular profiling challenges robustness of prognostic signature scores in multifocal prostate cancer.

96Background: Tissue based biomarkers are increasingly utilized in men diagnosed with low grade prostate cancer (PCa) to guide definitive management vs. active surveillance. PCa is uniquely multifocal, suggesting ideal prognostic biomarkers should be robust to both undersampling of a high grade component of a mixed-grade tumor focus, as well as unsampled multifocal high grade tumor foci. Methods: To assess the robustness of prognostic biomarkers to multifocality, we designed a comprehensive multiplexed targeted RNA sequencing assay (mxRNAseq) capable of assessing multiple classes of transcriptional alterations and deriving available prognostic signature scores (e.g. Prolaris CCP and OncotypeDX GPS). We applied this assay to a retrospective cohort of 176 FFPE tissue samples representing the range of PCa progression. Single candidate biomarkers and derived prognostic signatures were analyzed in multifocal cases with only low-grade disease as well as those with extreme grade differences across tumor foci. Re...