Study backs broader use of genetic testing in prostate cancer
Approximately half of prostate cancer patients with clinically actionable gene variants do not meet the NCCN guideline criteria for genetic testing, according to findings from the PROCLAIM trial published in European Urology Oncology.1,2
"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, MD.
The PROCLAIM study population included 958 patients with prostate cancer, of whom about half met the NCCN Prostate Cancer (version 2.2019) criteria for germline genetic testing (GGT) and the other half did not. These subgroups were categorized as the in criteria (IC) and out of criteria (OOC) groups, respectively.
All patients received clinical-grade GGT with a panel of 84 DNA damage repair (DDR) and other cancer-predisposition genes. Patients are at an increased risk of having early-onset and more aggressive prostate cancer if their panel results show pathogenic/likely pathogenic germline variants (PGVs) in DDR genes.
Among the 958 patient, GGT identified a total of 77 PGVs in 17 genes across 74 patients (7.7%). There was not a significant difference in the prevalence of PGVs between the IC and OOG groups at 8.8% vs 6.6%, respectively (odds ratio, 1.38; 95% CI, 0.85-2.23). Accordingly, the researchers determined that the NCCN criteria would have missed 41.9% (31/74) of patients with PGVs.
Overall, 81% (60/74) of the PGVs were potentially clinically actionable and thus some patients would be missing out on eligibility for FDA-approved targeted agents. For example, patients with certain PGVs would be eligible to receive PARP inhibitors, such as rucaparib (Rubra) or olaparib (Lynparza).
Also of note, the researchers reported that the NCCN criteria were less effective at predicting PGVs in non-white (predominantly Black) men.
"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," Neal Shore, MD, FACS, from the Carolina Urologic Research Center in Myrtle Beach, South Carolina, and the principal investigator of the study, stated in a press release.1
"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,” added Shore.1
Overall, the study enrolled 1008 patients with newly or previously diagnosed prostate cancer and no previous GGT across 14 US community urology clinics and 1 academic center between October 29, 2019, and August 23, 2021.The patient population was unselected for family history of cancer, age at diagnosis, or stage of disease.
Of these patients, 958 had all of the required information needed to determine their NCCN status. About half of these patients (51%; 486/958) met the NCCN criteria for GGT (IC group) and the other half (49%; 470/958) did not meet the criteria (OOC group).
Patient characteristics were similar between the OOC and IC groups. In the final study cohort of 958 patients, the median age at diagnosis was 65 and three-fourths (76%) of the patients were non-Hispanic White. The majority of patients had localized (83%) and/or low- or intermediate-risk disease (65%).
"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," W. Michael Korn, MD, chief medical officer for oncology at Invitae, stated in a press release.1 “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."
References
1. Clinical Trial Results Support Genetic Testing of All Patients with Prostate Cancer. Published online and accessed August 15, 2023. https://www.prnewswire.com/news-releases/clinical-trial-results-support-genetic-testing-of-all-patients-with-prostate-cancer-301900284.html
2. Shore N, Gazi M, Pieczonka C, Heron S, et al. Efficacy of National Comprehensive Cancer Network Guidelines in Identifying Pathogenic Germline Variants Among Unselected Patients with Prostate Cancer: The PROCLAIM Trial [published online ahead of print August 12, 2023]. Eur Urol Oncol. doi: 10.1016/j.euo.2023.07.008
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