From: Genetics of Prostate Cancer (PDQ®)
PDQ Cancer Information Summaries [Internet].
Bethesda (MD): National Cancer Institute (US); 2002-.
NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.
Table 2. Indications for Prostate Cancer Genetic Testing
| Philadelphia Prostate Cancer Consensus Conference (Giri et al. 2020)a [6] | Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic (Version 2.2024)b [3] | NCCN Prostate Cancer (Version 4.2023)c [4] | European Advanced Prostate Cancer Consensus Conference (Gillessen et al. 2017 [2] and Gillessen 2020 [8])d | |
|---|---|---|---|---|
| Family History Criteria | All men with prostate cancer from families meeting established testing or syndromic criteria for HBOC, hereditary prostate cancer, or Lynch syndrome | Men affected with prostate cancer who have a family history of the following: ≥1 FDR, SDR, or TDR (on the same side of the family) with breast cancer at age ≤50 y or with any of the following: triple-negative breast cancer, ovarian cancer, pancreatic cancer, high- or very-high-risk prostate cancer, male breast cancer, or metastatic prostate cancer at any age | Men affected with prostate cancer who have the following: ≥1 FDR, SDR, or TDR (on the same side of the family) with breast cancer at age ≤50 y, colorectal or endometrial cancer at age ≤50 y, male breast cancer at any age, ovarian cancer at any age, exocrine pancreatic cancer at any age, or metastatic, regional, very-high-risk, high-risk prostate cancer at any age | Men with a positive family history of prostate cancer [2] |
| Men affected with prostate cancer who have >2 close biological relatives with a cancer associated with HBOC, hereditary prostate cancer, or Lynch syndrome | Men affected with prostate cancer who have ≥3 FDRs, SDRs, or TDRs (on the same side of the family) with breast cancer or prostate cancer (any grade) at any age | Men affected with prostate cancer who have ≥1 FDR with prostate cancer at age ≤60 y (exclude relatives with clinically localized Grade Group 1 disease) | Men with a positive family history of other cancer syndromes (HBOC and/or pancreatic cancer and/or Lynch syndrome) [2] | |
| Men with an FDR who was diagnosed with prostate cancer at <60 y | Men with or without prostate cancer with an FDR who meets any of the criteria listed above (except when a man without prostate cancer has relatives who meet the above criteria solely for systemic therapy decision-making; these criteria may also be extended to an affected TDR if he/she is related to the patient through two male relatives) | Men affected with prostate cancer who have ≥2 FDRs, SDRs, or TDRs (on the same side of the family) with breast cancer or prostate cancer at any age (exclude relatives with clinically localized Grade Group 1 disease) | ||
| Men with relatives who died of prostate cancer | Men affected with prostate cancer who have ≥3 FDRs or SDRs (on the same side of the family) with the following Lynch syndrome-related cancers, especially if diagnosed at age <50 y: colorectal, endometrial, gastric, ovarian, exocrine pancreas, upper tract urothelial, glioblastoma, biliary tract, and small intestine | |||
| Men with a metastatic prostate cancer in an FDR | ||||
| Consider genetic testing in men with prostate cancer and Ashkenazi Jewish ancestry | Men with prostate cancer and Ashkenazi Jewish ancestry | Men with prostate cancer and Ashkenazi Jewish ancestry | ||
| Men with prostate cancer and a known family history of a pathogenic or likely pathogenic variant in one of the following genes: BRCA1, BRCA2, ATM, PALB2, CHEK2, MLH1, MSH2, MSH6, PMS2, or EPCAM | ||||
| Clinical/Pathological Features | Men with metastatic prostate cancer | Men with metastatic prostate cancer | Men with metastatic prostate cancer | Men with newly diagnosed metastatic prostate cancer (62% of panel voted in favor of genetic counseling/testing in a minority of selected patients) [8] |
| Men with stage T3a or higher prostate cancer | Men with high- or very-high-risk prostate cancer | Men with high-risk prostate cancer, very-high-risk prostate cancer, high-risk localized prostate cancer, or regional (node-positive) prostate cancer | ||
| Men with prostate cancer that has intraductal/ductal histology | Testing may be considered in men who have intermediate-risk prostate cancer with intraductal/cribriform histology at any age | Germline testing may be considered in men who have intermediate-risk prostate cancer with intraductal/cribriform histology at any age | ||
| Germline testing may be considered in men with prostate cancer AND a prior personal history of any of the following cancers: exocrine pancreatic, colorectal, gastric, melanoma, upper tract urothelial, glioblastoma, biliary tract, and small intestinal | Men with prostate cancer diagnosed at age <60 y [2] | |||
| Tumor Sequencing Characteristics | Men with prostate cancer whose somatic testing reveals the possibility of a germline variant in a cancer risk gene, especially BRCA2, BRCA1, ATM, and DNA MMR genes | Men with a pathogenic variant found on tumor genomic testing that may have clinical implications if it is also identified in the germline | Recommend tumor testing for pathogenic variants in homologous recombination genes in men with metastatic disease; consider tumor testing in men with regional prostate cancer | |
| Recommend MSI-high or dMMR tumor testing in men with metastatic castration-resistant prostate cancer; consider testing in men with regional or castration-sensitive metastatic prostate cancer |
dMMR = mismatch repair deficient; FDR = first-degree relative; HBOC = hereditary breast and ovarian cancer; MMR = mismatch repair; MSI = microsatellite instability; NCCN = National Comprehensive Cancer Network; SDR= second-degree relative; TDR= third-degree relative.
aGiri et al.: Specific genes to test include BRCA1/BRCA2, DNA MMR genes, ATM, and HOXB13 depending on various testing indications.
bNCCN Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic guidelines state that prostate cancer risk management is indicated for BRCA1 and BRCA2 carriers, but evidence for risk management is insufficient for other genes.
cNCCN Prostate Cancer guidelines specify that germline multigene testing includes at least the following genes: BRCA1, BRCA2, ATM, PALB2, CHEK2, MLH1, MSH2, MSH6, and PMS2. Including additional genes may be appropriate based on clinical context.
dGillessen et al. endorsed the use of large panel testing including homologous recombination and DNA MMR genes.