New Criteria for Inherited Prostate Cancer Genetic Testing

TON - March 2018, Vol 11, No 1 - Genetic Counseling, NCCN
Cristi Radford, MS, CGC

 

New Criteria for Inherited Prostate Cancer Genetic Testing

Similar to other disease sites, prostate cancer has seen a surge in genetic testing options. At least 3 clinical laboratories offer targeted panels for inherited prostate cancer. In addition, other laboratories analyze genes associated with prostate cancer risk, although they are not part of a targeted, inherited prostate cancer panel. Because these panels are relatively new, guidelines about who should be tested for inherited prostate cancer have been limited.

The current National Comprehensive Cancer Network (NCCN) guidelines for Genetic/Familial High-Risk Assessment: Breast and Ovarian (version 1.2018) include prostate cancer, prostate cancer with a Gleason score ≥7, and metastatic prostate cancer in its BRCA1/2 testing algorithm.1 In addition, the NCCN Prostate Cancer Early Detection (version 2.2017) guidelines mention asking patients about the presence of a BRCA1/2 mutation.2 However, neither of these guidelines specifically mentions testing for other genes associated with prostate cancer risk.

In addition to being important for prostate cancer risk stratification and surveillance, and for risk reduction management plans for associated cancers, inherited prostate cancer testing also has a role in disease management. It is estimated at least 1 in 9 men with metastatic prostate cancer carry a germline mutation.3 Studies have shown that men who carry a DNA-repair mutation may benefit from the use of poly(ADP-ribose) polymerase inhibitors,4,5 and that men with mutations in genes associated with Lynch syndrome could potentially benefit from the use of immune checkpoint inhibitors for microsatellite instability.6 Therefore, similar to other disease sites, genetic testing for prostate cancer has both risk reduction and disease management implications.

To help address the role of genetic testing in prostate cancer disease management, the NCCN Clinical Practice Guidelines in Oncology were updated in February 2018 to include germline recommendations.7 At the time of initial prostate cancer diagnosis, it is recommended that risk stratification be performed based on staging information and family history. Germline testing is recommended for men falling into high, very high, regional, or metastatic risk groups and suggested to be considered in men falling into low or intermediate risk categories with a family history consisting of a brother, father, or multiple family members diagnosed with prostate cancer 1 <60 years of age; familial DNA repair gene abnormality; and/or > relative with breast, ovarian, pancreatic, colorectal, endometrial, gastric, ovarian, pancreatic, small bowel, urothelial, kidney, or bile duct cancer. Additionally, tumor testing for microsatellite instability or immunohistochemistry for the mismatch repair genes and germline/somatic testing of BRCA1/2, ATM, PALB2, and FANCA should be considered in certain castration-resistant situations and positive results should be referred for genetic counseling.

Before the recent NCCN updates addressing the role of genetic testing in disease management, the Philadelphia Prostate Cancer Consensus Conference 2017 was held to provide guidance on which patients should be tested for inherited prostate cancer risk.8 Participants included those involved in early detection, treatment, research, patient advocacy, and genetic counseling for prostate cancer. A statement was considered to have strong consensus if ≥75% of participants agreed, moderate consensus if 50% to 74% agreed, and lack of consensus if <50% agreed. The genes in current panels that most often demonstrated a strong consensus for testing were HOXB13, BRCA1/2, and those associated with Lynch syndrome (ie, MLH1, MSH2, MSH6, PMS2, EPCAM).

There was strong consensus that any man with prostate cancer who meets established testing or syndromic criteria for HOXB13, BRCA1/2, or Lynch syndrome, or who has ≥2 relatives on the same side of the family with a cancer in the associated syndromes should undergo genetic counseling and genetic testing.8 Strong consensus was also present for men with prostate cancer whose tumor sequencing results had mutations in cancer risk genes to undergo germline testing.

There was moderate consensus that all men with metastatic prostate cancer should undergo genetic testing.8 However, for this same patient population, there was strong consensus that testing should include BRCA1/2, and moderate consensus that it should include ATM.

These consensus criteria, along with the recent NCCN Clinical Practice Guidelines updates, demonstrate that experts feel genetic testing is warranted in patients for several genes associated with prostate cancer risk—and not solely BRCA1/2. As with all criteria, as more is learned about the genes associated with prostate cancer risk and management options, they will likely expand and evolve.

References

  1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Genetic/ Familial High-Risk Assessment: Breast and Ovarian. Version 1.2018. October 3, 2017. www.nccn.org/professionals/physician_gls/pdf/genetics_screening.pdf. Accessed February 5, 2018.
  2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer Early Detection. Version 2.2017. September 15, 2017. www.nccn.org/professionals/physician_gls/pdf/prostate_detection.pdf. Accessed February 5, 2018.
  3. Pritchard CC, Mateo J, Walsh MF, et al. Inherited DNA-repair gene mutations in men with metastatic prostate cancer. N Engl J Med. 2016;375:443-453.
  4. Mateo J, Carreira S, Sandhu S, et al. DNA-repair defects and olaparib in metastatic prostate cancer. N Engl J Med. 2015;373:1697-1708.
  5. Sandhu SK, Omlin A, Hylands L, et al. Poly (ADP-ribose) polymerase (PARP) inhibitors for the treatment of advanced germline BRCA2 mutant prostate cancer. Ann Oncol. 2013;24:1416-1418.
  6. Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357:409-413.
  7. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer. Version 1.2018. February 14, 2018. www.nccn.org/professionals/physician_gls/pdf/genetics_screening.pdf. Accessed February 26, 2018.
  8. Giri VN, Knudsen KE, Kelly WK, et al. Role of genetic testing for inherited prostate cancer risk: Philadelphia prostate cancer consensus conference 2017. J Clin Oncol. 2018;36:414-424.
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Last modified: April 25, 2018