Implementation of Germline Testing for Prostate Cancer: Philadelphia Prostate Cancer Consensus Conference 2019
Authors: Giri Veda N. , Knudsen Karen E. , Kelly William K. , Cheng Heather H. , Cooney Kathleen A. , Cookson Michael S. , Dahut William , Weissman Scott , Soule Howard R. , Petrylak Daniel P. , Dicker Adam P. , AlDubayan Saud H. , Toland Amanda E. , Pritchard Colin C. , Pettaway Curtis A. , Daly Mary B. , Mohler James L. , Parsons J. Kellogg , Carroll Peter R. , Pilarski Robert , Blanco Amie , Woodson Ashley , Rahm Alanna , Taplin Mary-Ellen , Polascik Thomas J. , Helfand Brian T. , Hyatt Colette , Morgans Alicia K. , Feng Felix , Mullane Michael , Powers Jacqueline , Concepcion Raoul , Lin Daniel W. , Wender Richard , Mark James Ryan , Costello Anthony , Burnett Arthur L. , Sartor Oliver , Isaacs William B. , Xu Jianfeng , Weitzel Jeffrey , Andriole Gerald L. , Beltran Himisha , Briganti Alberto , Byrne Lindsey , Calvaresi Anne , Chandrasekar Thenappan , Chen David Y. T. , Den Robert B. , Dobi Albert , Crawford E. David , Eastham James , Eggener Scott , Freedman Matthew L. , Garnick Marc , Gomella Patrick T. , Handley Nathan , Hurwitz Mark D. , Izes Joseph , Karnes R. Jeffrey , Lallas Costas , Languino Lucia , Loeb Stacy , Lopez Ana Maria , Loughlin Kevin R. , Lu-Yao Grace , Malkowicz S. Bruce , Mann Mark , Mille Patrick , Miner Martin M. , Morgan Todd , Moreno Jose , Mucci Lorelei , Myers Ronald E. , Nielsen Sarah M. , O’Neil Brock , Pinover Wayne , Pinto Peter , Poage Wendy , Raj Ganesh V. , Rebbeck Timothy R. , Ryan Charles , Sandler Howard , Schiewer Matthew , Scott E. Michael D. , Szymaniak Brittany , Tester William , Trabulsi Edouard J. , Vapiwala Neha , Yu Evan Y. , Zeigler-Johnson Charnita , Gomella Leonard G. 
Published: June 2020

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.