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A Pilot Study of Clinical Targeted Next Generation Sequencing for Prostate Cancer: Consequences for Treatment and
Heather H Cheng1,2, Nola Klemfuss3, Bruce Montgomery1,2
1Division of Oncology, Department of Medicine, University of Washington, Seattle, Washington.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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 76:1303-1311, 2016. © 2016 Wiley Periodicals, Inc.
Insights
Targeted next generation sequencing (tNGS) in prostate cancer management identified actionable mutations and potential germline cancer predisposition genes in 81% of patients. This approach may guide immediate and future treatment decisions.
Area of Science:
- Oncology
- Genetics
- Genomic Medicine
Background:
- Prostate cancer management is increasingly incorporating targeted next-generation sequencing (tNGS).
- Clinical utility of tNGS for prostate cancer is not yet widespread.
- This study aimed to assess the current clinical utility of tNGS in prostate cancer management.
Purpose of the Study:
- To determine the clinical utility of targeted next-generation sequencing (tNGS) for prostate cancer management.
- To evaluate the impact of tNGS on therapeutic decision-making in prostate cancer patients.
- To identify actionable mutations and germline predisposition genes in prostate cancer.
Main Methods:
- Recruitment of prostate cancer patients with unusual features by genitourinary medical oncologists.
- Performance of UW-OncoPlex tNGS on formalin-fixed, paraffin-embedded (FFPE) tumor samples.
- Discussion of tNGS results at a multidisciplinary precision tumor board for treatment planning.
Main Results:
- 42 patients had reportable tNGS results, revealing mutations in known prostate cancer genes and others with available targeted treatments.
- 10% of cases (4/42) led to direct treatment changes; 81% (34/42) showed some level of treatment actionability.
- 24% of patients (10/42) had suspected germline mutations in moderate or high-penetrance cancer risk genes (e.g., BRCA2, TP53).
Conclusions:
- Targeted NGS tumor sequencing can guide current and future treatment options for prostate cancer.
- A significant subset of patients harbored germline mutations in cancer predisposition genes, impacting clinical management for patients and their families.
- tNGS demonstrates potential for improving therapeutic strategies and identifying hereditary cancer risks in prostate cancer patients.
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