Implementation of Germline Testing for Prostate Cancer: Philadelphia Prostate Cancer Consensus Conference 2019

Veda N Giri 1 2 3, Karen E Knudsen 3, William K Kelly 1, Heather H Cheng 4, Kathleen A Cooney 5, Michael S Cookson 6, William Dahut 7, Scott Weissman 8, Howard R Soule 9, Daniel P Petrylak 10, Adam P Dicker 11, Saud H AlDubayan 12, Amanda E Toland 13, Colin C Pritchard 14, Curtis A Pettaway 15, Mary B Daly 16, James L Mohler 17, J Kellogg Parsons 18, Peter R Carroll 19, Robert Pilarski 20, Amie Blanco 21, Ashley Woodson 15, Alanna Rahm 22, Mary-Ellen Taplin 12, Thomas J Polascik 23, Brian T Helfand 24, Colette Hyatt 25, Alicia K Morgans 26, Felix Feng 27, Michael Mullane 28, Jacqueline Powers 29, Raoul Concepcion 30, Daniel W Lin 31, Richard Wender 32, James Ryan Mark 2, Anthony Costello 33, Arthur L Burnett 34, Oliver Sartor 35, William B Isaacs 36, Jianfeng Xu 24, Jeffrey Weitzel 37, Gerald L Andriole 38, Himisha Beltran 39, Alberto Briganti 40, Lindsey Byrne 41, Anne Calvaresi 2, Thenappan Chandrasekar 2, David Y T Chen 16, Robert B Den 11, Albert Dobi 42, E David Crawford 43, James Eastham 44, Scott Eggener 45, Matthew L Freedman 39, Marc Garnick 46, Patrick T Gomella 47, Nathan Handley 1, Mark D Hurwitz 11, Joseph Izes 2, R Jeffrey Karnes 48, Costas Lallas 2, Lucia Languino 3, Stacy Loeb 49, Ana Maria Lopez 1, Kevin R Loughlin 50, Grace Lu-Yao 1, S Bruce Malkowicz 51, Mark Mann 2, Patrick Mille 1, Martin M Miner 52, Todd Morgan 53, Jose Moreno 54, Lorelei Mucci 55, Ronald E Myers 1, Sarah M Nielsen 45, Brock O'Neil 56, Wayne Pinover 57, Peter Pinto 47, Wendy Poage 58, Ganesh V Raj 59, Timothy R Rebbeck 55, Charles Ryan 60, Howard Sandler 61, Matthew Schiewer 3, E Michael D Scott 62, Brittany Szymaniak 63, William Tester 1, Edouard J Trabulsi 2, Neha Vapiwala 51, Evan Y Yu 64, Charnita Zeigler-Johnson 1, Leonard G Gomella 2

Affiliations

PMID: 32516092
DOI: 10.1200/JCO.20.00046

Abstract

Purpose: Germline testing (GT) is a central feature of prostate cancer (PCA) treatment, management, and hereditary cancer assessment. Critical needs include optimized multigene testing strategies that incorporate evolving genetic data, consistency in GT indications and management, and alternate genetic evaluation models that address the rising demand for genetic services.

Methods: A multidisciplinary consensus conference that included experts, stakeholders, and national organization leaders was convened in response to current practice challenges and to develop a genetic implementation framework. Evidence review informed questions using the modified Delphi model. The final framework included criteria with strong (> 75%) agreement (Recommend) or moderate (50% to 74%) agreement (Consider).

Results: Large germline panels and somatic testing were recommended for metastatic PCA. Reflex testing-initial testing of priority genes followed by expanded testing-was suggested for multiple scenarios. Metastatic disease or family history suggestive of hereditary PCA was recommended for GT. Additional family history and pathologic criteria garnered moderate consensus. Priority genes to test for metastatic disease treatment included BRCA2, BRCA1, and mismatch repair genes, with broader testing, such as ATM, for clinical trial eligibility. BRCA2 was recommended for active surveillance discussions. Screening starting at age 40 years or 10 years before the youngest PCA diagnosis in a family was recommended for BRCA2 carriers, with consideration in HOXB13, BRCA1, ATM, and mismatch repair carriers. Collaborative (point-of-care) evaluation models between health care and genetic providers was endorsed to address the genetic counseling shortage. The genetic evaluation framework included optimal pretest informed consent, post-test discussion, cascade testing, and technology-based approaches.

Conclusion: This multidisciplinary, consensus-driven PCA genetic implementation framework provides novel guidance to clinicians and patients tailored to the precision era. Multiple research, education, and policy needs remain of importance.