A pilot study of clinical targeted next generation sequencing for prostate cancer: Consequences for treatment and genetic counseling.

Targeted next generation sequencing (tNGS) is increasingly used in oncology for therapeutic decision-making, but is not yet widely used for prostate cancer. The objective of this study was to determine current clinical utility of tNGS for prostate cancer management.

Seven academic genitourinary medical oncologists recruited and consented patients with prostate cancer, largely with unusual clinical and/or pathologic features, from 2013 to 2015. UW-OncoPlex was performed on formalin-fixed, paraffin-embedded (FFPE) primary tumors and/or metastatic biopsies. Results were discussed at a multidisciplinary precision tumor board prior to communicating to patients. FFPE tumor DNA was extracted for tNGS analysis of 194 cancer-associated genes. Results, multidisciplinary discussion, and treatment changes were recorded.

Forty-five patients consented and 42 had reportable results. Findings included mutations in genes frequently observed in prostate cancer. We also found alterations in genes where targeted treatments were available and/or in clinical trials. 4/42 (10%) cases, change in treatment directly resulted from tNGS and multidisciplinary discussion. In 30/42 (71%) cases additional options were available but not pursued and/or were pending. Notably, 10/42 (24%) of patients harbored suspected germline mutations in moderate or high-penetrance cancer risk genes, including BRCA2, TP53, ATM, and CHEK2. One patient's tumor had bi-allelic MSH6 mutation and microsatellite instability. In total, 34/42 (81%) cases resulted in some measure of treatment actionability. Limitations include small size and limited clinical outcomes.

Targeted NGS tumor sequencing may help guide immediate and future treatment options for men with prostate cancer. A substantial subset had germline mutations in cancer predisposition genes with potential clinical management implications for men and their relatives. Prostate. 9999:1-9, 2016. © 2016 Wiley Periodicals, Inc.

The Prostate. 2016 Jun 21 [Epub ahead of print]

Heather H Cheng, Nola Klemfuss, Bruce Montgomery, Celestia S Higano, Michael T Schweizer, Elahe A Mostaghel, Lisa G McFerrin, Evan Y Yu, Peter S Nelson, Colin C Pritchard

Division of Oncology, Department of Medicine, University of Washington, Seattle, Washington., Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, Washington., Division of Oncology, Department of Medicine, University of Washington, Seattle, Washington., Division of Oncology, Department of Medicine, University of Washington, Seattle, Washington., Division of Oncology, Department of Medicine, University of Washington, Seattle, Washington., Division of Oncology, Department of Medicine, University of Washington, Seattle, Washington., Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, Washington., Division of Oncology, Department of Medicine, University of Washington, Seattle, Washington., Division of Oncology, Department of Medicine, University of Washington, Seattle, Washington., Department of Laboratory Medicine, University of Washington, Seattle, Washington.