Table 2. NCCN version 2; 2020 recommendations for genetic testing and treatment strategies [9].

Germline testing	Somatic testing
Recommended	Recommended	Considered
• Strong positive family history • High-risk or very high-risk localized PCa or metastatic PCa regardless of family history • Intraductal histology • Ashkenazi Jewish ancestry	• Patients with localized or metastatic PCa • Patients with low and favorable intermediate risk PCa and life expectancy ≥10 years	NA
• Regional (Any T, N1, M0)	NA	• Regional (Any T, N1, M0) • Tumor test for HRR, MSI, and dMMR
• Metastatic (Any T, any N, M1)	• Metastatic (Any T, any N, M1) • Tumor test for HRRm	• Metastatic (Any T, any N, M1) • Tumor test for MSI or dMMR
Recommendations for specific HRR gene testing
• Testing should include BRCA1/2, ATM, PALB2, and CHEK2 HRR genes	• Testing should include BRCA1/2, ATM, PALB2, CHEK2, FANCA, RAD51D, and CDK12 HRR genes • If somatic HRR mutations are identified, patients should be referred for genetic counseling
Treatment strategy
• Olaparib is a treatment option (category 1 recommendation) for patients with mCRPC and a pathogenic mutation (germline and/somatic) in a HRR gene (BRCA1/2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D, or RAD54L), who have been treated with androgen-receptor directed therapy. Patients with PPP2R2A mutations in the PROFOUND trial experienced an unacceptable risk-benefit profile. Therefore, olaparib is not recommended in patients with PPP2R2A mutations. • Rucaparib is a treatment option (category 2A recommendation) for mCRPC and a pathogenic BRCA1/2 mutation (germline and/or somatic) who have been treated with androgen receptor-directed therapy and a taxane based chemotherapy. If the patient is not fit for chemotherapy, rucaparib can be considered even if taxanebased therapy has not been given.

Abbreviations: ATM: ataxia-telangiectasia mutated; BRCA: breast cancer gene; CHEK2: checkpoint kinase 2; dMMR: mismatch repair; DNA: deoxyribonucleic acid; FANCA: Fanconi anemia complementation group A; MSI: microsatellite instability; NCCN: National Comprehensive Cancer Network; PALB2: partner and localizer of BRCA2; PCa: prostate cancer; PPP2R2A: Protein Phosphatase 2 Regulatory Subunit Balpha.