Hi, I’m Professor Phil Cornford of Liverpool University Hospitals in the UK and Vice Chair of the EAU Prostate Cancer Guidelines Panel. This series of videos has been co-created in association with ecancer. 

Around 20-25% of patients with advanced prostate cancer will harbour a HRR gene mutation and be eligible for the use of PARP inhibitors, but they need to be identified first. The AUA, ESMO, the NCCN, and the EAU guidelines recommend genetic testing (somatic and/or germline) for patients with metastatic disease, men with high risk disease and a family member diagnosed under the age of 60, or with a significant family history of prostate cancer. Men with a strong family history of breast, ovarian or prostate cancer who have a family member with a BRCA mutation, can be referred for genetic testing on the NHS in the UK but services vary worldwide.

Any commercially available analytically and clinically validated assay evaluating tumour, circulating tumour DNA or a germline assay may be used to identify patients for treatment with PARP inhibitors. Once identified, NCCN guidelines recommend olaparib as an option for patients with metastatic castration-resistant prostate cancer. Previous androgen receptor-directed therapy and an HRR mutation regardless of prior docetaxel therapy.

The HRR genes to be considered for use of olaparib are BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D and RAD54L. 

ESMO and EAU guidelines recommend olaparib to be considered after new hormonal agents for patients with metastatic castration-resistant prostate cancer with alterations in BRCA1 or BRCA2, in line with the EMA licence.

Careful monitoring of complete blood counts, and renal function is required. Potential transfusion support and/or dose reduction as needed for severe anaemia or intolerance are recommended by the NCCN during olaparib therapy. 

The NCCN guidelines also recommend rucaparib as an option for patients with metastatic castration-resistant prostate cancer prior to treatment with a novel hormone therapy and a BRCA1 or BRCA2 mutation. If the patient is not fit for chemotherapy, rucaparib can be considered even if taxane-based therapy has not been given. The preferred method of selecting patients for rucaparib treatment is a somatic analysis of BRCA1 and BRCA2 using a circulating tumour DNA sample. 

Careful monitoring of complete blood count, hepatic and renal function, along with potential transfusion support and/or dose reduction as needed for severe anaemia or intolerance is recommended.