On August 15, 2023 Invitae (NYSE: NVTA), a leading medical genetics company, reported findings from its PROCLAIM trial, published in European Urology Oncology, showing that almost half of prostate cancer patients with clinically actionable pathogenic/likely pathogenic germline variants (PGVs) could be missing out on genetics-informed care due to restrictive criteria for genetic testing (Press release, Invitae, AUG 15, 2023, View Source [SID1234634425]).

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In this prospective, observational study, nearly 1,000 men with prostate cancer unselected for family history of cancer, age at diagnosis or stage of disease, underwent germline genetic testing of 84 cancer predisposition genes under the care of urologists across the U.S., primarily in community clinics. In this study, 51% of patients with prostate cancer met National Comprehensive Cancer Network (NCCN) guidelines and 49% did not. The diagnostic yield of germline genetic testing between these two patient groups was compared.

"Real world evidence suggests that less than 15% of prostate cancer patients who could benefit from genetics-informed care undergo genetic testing, in part due to complicated and prohibitive testing guidelines," said Neal Shore, M.D., F.A.C.S., from the Carolina Urologic Research Center in Myrtle Beach, South Carolina, and the principal investigator of the study. "We found no statistically significant difference in the diagnostic yield of PGVs between those who met NCCN guidelines and those who did not, suggesting there are a significant number of patients with PGVs, many of which are targets for precision therapies, who are being missed when adhering to current NCCN guidelines for genetic testing."

Among nearly 1,000 patients (median age at diagnosis was 65 years), 65% had low-or intermediate-risk disease. A total of 77 PGVs in 17 genes were identified in 7.7% of the cohort. No significant difference was found in the prevalence of PGVs (8.8%) among the 51% of patients who met 2019 NCCN prostate criteria versus the remaining 49% who did not (6.6%), indicating that these criteria would miss 41.9% of patients with PGVs.

The data show nearly 80% of men with PGVs had potentially clinically actionable variants, including those in genes with eligibility for approved precision therapies or clinical treatment trials. When stratified by self-reported ethnicity, non-white (predominantly Black) men who were out-of-criteria had a higher number of PGVs than those who were in-criteria, suggesting current criteria disproportionately disadvantage historically underrepresented populations from obtaining critical genetic information. This disparity is particularly disturbing given Black men with prostate cancer are known to present with more aggressive disease.

"According to the American Cancer Society, prostate cancer is the second most common cancer in American men. Considering how common this diagnosis is, it’s critical that individuals are offered the proper screenings and access to necessary preventive measures to assess their risk and detect cancer as early as possible," said W. Michael Korn, M.D., chief medical officer for oncology at Invitae. "Through this study, we are seeing how genetic testing can play a vital role in understanding a prostate cancer diagnosis, as it can inform different types of treatment that might work best for a patient’s individual needs."

The findings support broadening the current guidelines and offering germline genetic testing to all patients with prostate cancer. This could change the standard of medical care for these patients, expanding access to precision therapies, clinical trial treatments and enhanced screening.