Metastatic castration-resistant prostate cancer is a heterogeneous disease that is often associated with a poor outcome. Loss of function mutations in genes involved in homologous recombination repair or DNA damage checkpoints, including BRCA1, BRCA2 and ATM, are identified in ~16% of patients. Prostate and other cancers with a mutation in one of these genes have been shown to be sensitive to treatment with poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors.
Sequencing panel testing is offered to patients in BC with metastatic castration-resistant prostate cancer to identify mutations in ATM, BRCA1, and BRCA2. Patients with a pathogenic or likely pathogenic mutation identified in one of these genes may be eligible to receive PARP inhibitor therapy.
The genes in these sequencing panels are strongly associated with inherited cancer predisposition syndromes and so patients with a mutation in their genomic DNA have an increased risk to develop other cancers. These patients would benefit from genetic counselling and a referral to the Hereditary Cancer Program at BC Cancer is recommended.
The results of this testing are not a substitute for germline screening. If a patient has clinical features or a personal or family history suggestive of an inherited syndrome then a Hereditary Cancer referral should be made, regardless of the results of this testing.
Testing in the context of metastatic prostate cancer is available using either our Oncopanel multigene NGS panel or our Prostate ctDNA panel.
- The Oncopanel assay is performed on FFPE tumour tissue. This test can detect mutations in ATM, BRCA1, and BRCA2, as well as a variety of predictive and prognostic genes including and genes associated with inherited cancer predisposition.
- The Prostate ctDNA panel is performed on ccfDNA isolated from peripheral blood plasma. This test can detect mutations in ATM, BRCA1 and BRCA2.
The optimal testing strategy begins with Oncopanel analysis of FFPE tumour tissue specimens. Please select and send two FFPE specimen blocks due to the higher failure rate of this tumour type. Please note that since most bone biopsies have been decalcified they are not suitable for molecular testing.
If FFPE tissue is unavailable, or if FFPE analysis fails to produce an interpretable result, Prostate ctDNA testing can be ordered on peripheral blood specimens collected in Streck tubes.
Hereditary testing is available for patients with metastatic prostate cancer (see our Hereditary Cancer page for details).