Role of Genetic Testing for Inherited Prostate Cancer Risk: Philadelphia Prostate Cancer Consensus Conference 2017.

Giri VN1, Knudsen KE1, Kelly WK1, Abida W1, Andriole GL1, Bangma CH1, Bekelman JE1, Benson MC1, Blanco A1, Burnett A1, Catalona WJ1, Cooney KA1, Cooperberg M1, Crawford DE1, Den RB1, Dicker AP1, Eggener S1, Fleshner N1, Freedman ML1, Hamdy FC1, Hoffman-Censits J1, Hurwitz MD1, Hyatt C1, Isaacs WB1, Kane CJ1, Kantoff P1, Karnes RJ1, Karsh LI1, Klein EA1, Lin DW1, Loughlin KR1, Lu-Yao G1, Malkowicz SB1, Mann MJ1, Mark JR1, McCue PA1, Miner MM1, Morgan T1, Moul JW1, Myers RE1, Nielsen SM1, Obeid E1, Pavlovich CP1, Peiper SC1, Penson DF1, Petrylak D1, Pettaway CA1, Pilarski R1, Pinto PA1, Poage W1, Raj GV1, Rebbeck TR1, Robson ME1, Rosenberg MT1, Sandler H1, Sartor O1, Schaeffer E1, Schwartz GF1, Shahin MS1, Shore ND1, Shuch B1, Soule HR1, Tomlins SA1, Trabulsi EJ1, Uzzo R1, Vander Griend DJ1, Walsh PC1, Weil CJ1, Wender R1, Gomella LG1.

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Abstract

Purpose Guidelines are limited for genetic testing for prostate cancer (PCA). The goal of this conference was to develop an expert consensus-driven working framework for comprehensive genetic evaluation of inherited PCA in the multigene testing era addressing genetic counseling, testing, and genetically informed management. Methods An expert consensus conference was convened including key stakeholders to address genetic counseling and testing, PCA screening, and management informed by evidence review. Results Consensus was strong that patients should engage in shared decision making for genetic testing. There was strong consensus to test HOXB13 for suspected hereditary PCA, BRCA1/2 for suspected hereditary breast and ovarian cancer, and DNA mismatch repair genes for suspected Lynch syndrome. There was strong consensus to factor BRCA2 mutations into PCA screening discussions. BRCA2 achieved moderate consensus for factoring into early-stage management discussion, with stronger consensus in high-risk/advanced and metastatic setting. Agreement was moderate to test all men with metastatic castration-resistant PCA, regardless of family history, with stronger agreement to test BRCA1/2 and moderate agreement to test ATM to inform prognosis and targeted therapy. Conclusion To our knowledge, this is the first comprehensive, multidisciplinary consensus statement to address a genetic evaluation framework for inherited PCA in the multigene testing era. Future research should focus on developing a working definition of familial PCA for clinical genetic testing, expanding understanding of genetic contribution to aggressive PCA, exploring clinical use of genetic testing for PCA management, genetic testing of African American males, and addressing the value framework of genetic evaluation and testing men at risk for PCA-a clinically heterogeneous disease.