Patients with prostate cancer that harbour certain homologous recombination repair (HRR) alterations are more likely to respond to PARP inhibition. Treatment of patients with metastatic castration-resistant prostate cancer (CRPC) with the PARP inhibitors olaparib or rucaparib is contingent upon the presence of these genomic events. Diagnostic testing should be performed to identify patients with tumours harbouring aberrations in HRR—particularly BRCA1 and BRCA2 mutations, for which most evidence for efficacy is available—which may respond to these targeted treatments. Increased awareness of recommendations for testing is critical for the selection and care of these patients.[1]
An HRR alteration in a tumour can be germline or solely somatic in origin. If a mutation is germline in origin, then it can be identified in DNA isolated from whole blood, leukocytes or saliva (blood/saliva test positive). Somatic mutation status is determined by tumour or plasma (circulating cell-free tumour DNA) sequencing. While the likelihood of a mutation being germline may be ascertained from somatic testing, most somatic tests do not currently report this information. Resolution of germline status therefore often requires a second test for patients with mutations identified through tumour or plasma testing.
Find out more about genetics and genetic testing in prostate cancer
- Clinical considerations and prognostic value
- HRR pathway gene mutations
- CDK12 mutations
- MMR pathway gene mutations
- Distribution and prevalence of mutations in metastatic prostate cancer
- Genomic tests and considerations for patient selection
- Testing algorithm
- Guidelines for genetic testing
[1] Shore N, Ionescu-Ittu R, Yang L, et al. Real-world patterns of genomic testing in patients with metastatic castration-resistant prostate cancer. Ann Oncol. 2020;31(S4):S526-527.