Integration of genomic classification and clinical characteristics predicts survival in metastatic prostate cancer

PurposeTumor comprehensive genomic profiling (CGP) has revolutionized cancer care and identifies patients for biomarker-specific therapy. In metastatic hormone-sensitive prostate cancer (mHSPC), CGP is not currently prognostic and no DNA-based genomic classification exists that accounts for combinations of alterations. We developed a DNA-based CGP classification that is prognostic for overall survival (OS) and could inform treatment. MethodsRetrospective cross-sectional study using multivariable models to develop a clinico-genomic prognostic risk classification in U.S. Veterans diagnosed with synchronous mHSPC. Primary outcome was overall survival (OS) from time of metastatic diagnosis. Results7201 Veterans with metastatic prostate cancer who underwent CGP were identified. There were 2484 Veterans (median [IQR] age 72 [67-77] years) with synchronous mHSPC and tissue CGP, which were divided into training and testing datasets. 16 genes associated with survival were identified and favorable, intermediate, and unfavorable genomic prognostication groups were created based upon mortality risk to generate the STRATOS-P classification. In a multivariable model, classification into intermediate and unfavorable groups was associated with increased mortality relative to the favorable group (aHR 1.54 [95% CI 1.33-1.78]; aHR 2.37 [95% CI 1.97-2.485], respectively), demonstrating an average AUC of 0.83. In an external validation cohort of non-Veterans, intermediate and unfavorable classifications were associated with increased mortality (aHR 2.45 [95% CI 1.87-3.21]; aHR 4.37 [95% CI 3.06-6.22], respectively) with an AUC of 0.79. The intermediate and unfavorable genomic prognostication groups were also associated with increased mortality across multiple disease states including synchronous and metachronous diagnoses, castration-resistance, and analyte type. ConclusionsIn metastatic prostate cancer, tumor DNA genomic alterations are prognostic for OS. The STRATOS-P classification is a validated prognostic tool that has the potential to guide decision-making in mHSPC.