Results from a recent cross-sectional study suggest that National Comprehensive Cancer Network (NCCN) guidelines and Gleason scores are not reliable for stratifying patients with prostate cancer by whether they do or do not have pathogenic germline variants, prompting researchers to suggest that expanding and simplifying testing guidelines will improve medical management of these patients (JAMA Oncol. 2019 Feb 7. Epub ahead of print).

“Inherited risk for prostate cancer is associated with aggressive disease and poorer outcomes, indicating a critical need for increased genetic screening to identify disease-causing variants that can pinpoint individuals at increased risk for metastatic castration-resistant prostate cancer,” explained lead investigator Piper Nicolosi, PhD, Invitae Corporation, San Francisco, California, and colleagues.

Thus, using data from 3607 men with a history of prostate cancer who underwent germline genetic testing between 2013 and 2018, Dr Nicolosi and colleagues conducted a study to identify positive germline variants and assess the efficacy of current practice guidelines in identifying individuals at increased risk for prostate cancer. Men included in the study had a mean age at testing and at diagnosis of 67 years and 60 years, respectively.

Data were analyzed between February 2017 and August 2018, and referral-based testing was performed at a diagnostic laboratory certified by the Clinical Laboratory Improvement Amendments and College of American Pathologists.

Of the 3607 men included in the study who had a diagnosis of prostate cancer and were referred for genetic testing, 620 (17.2%) had positive germline variants, of which only 30.7% were variants in BRCA1/2.

In 30 (4.5%) patients, Dr Nicolosi and colleagues observed positive variants in HOXB13, a gene associated only with prostate cancer risk. Among the total population, they identified DNA mismatch repair variants with substantial known therapeutic implications in 1.74% of variants.

Of note, 229 (37%) men with positive variants would not have been approved for genetic testing had they been selected in accordance with the NCCN genetic/familial breast and ovarian guidelines for patients with prostate cancer.

“Current NCCN guidelines and Gleason scores cannot reliably stratify patients with prostate cancer for the presence or absence of pathogenic germline variants,” Dr Nicolosi and colleagues concluded.

“Most positive genetic test results identified in this study have important management implications for patients and their families, which underscores the need to revisit current guidelines,” they said.—Hina Khaliq