Alan H. Bryce, MD

Alan H. Bryce, MD, Medical Director of the Genomic Oncology Clinic at Mayo Clinic Arizona in Scottsdale, discusses genetic testing, next generation DNA sequencing, and the genetic diversity of prostate cancer (PCa) in regard to treatment. He begins by reviewing the germline BRCA mutations, stating that BRCA1 and BRCA2 mutations individually make up fewer than 1.3% of all cases of localized PCa. Dr. Bryce then discusses BRCA2 in detail, focusing on how BRCA2 carriers are considered high risk by the NCCN guidelines, which recommend PSA screening discussions to start at age 45. He evaluates traditional guidelines in the context of germline mutations, finding that genetic testing and Gleason score guidelines do not reliably identify PCa patients for the presence/absence of high-risk germline mutations. Dr. Bryce then discusses the mutational landscape by disease state, displaying how PCa evolves as it advances to become metastatic and castration resistant and supporting the idea that a genomic understanding of an individual’s disease is key to treatment. He reviews the approval of olaparib, a PARP inhibitor, and the PROfound trial. Dr. Bryce concludes that inherited prostate cancer risk syndromes are under-recognized, both in practice and in research, that PCa is genetically diverse, that the impact of treatments on tumor evolution should be evaluated, and that multiple new pathways for therapeutic targeting have been identified.