This publication is the third and final analysis from the PROCLAIM Trial, and lends additional evidence for a universal germline testing approach for patients with PCa. Previous work demonstrated that the prevalence of pathogenic germline variants between patients who met testing criteria and those who did not meet criteria was not statistically different (8.8% vs. 6.6%, respectively), and nearly 50% of patients with these variants would have been missed by guideline-restricted testing. More than 80% of the identified variants were potentially clinically actionable. Strikingly, pathogenic variants were significantly more frequent in White compared to non-White patients (9.0% vs. 2.0%, respectively), but among non-White patients, variant prevalence was actually higher in patients who did not meet criteria (4.0%) compared to those who did meet criteria (1.8%). This suggests that guidelines may be unintentionally creating barriers to genetics-informed care in underrepresented and underserved populations.1
We further demonstrated the clinical utility of germline testing in the second analysis of the PROCLAIM Trial, which examined clinician-reported recommendations. This study showed that germline test results influenced care for patients with PCa, including those who did not meet testing criteria and those with low-risk localized disease. However, this study did uncover higher than anticipated rates of clinical management changes in patients with uncertain (variant of uncertain significance, VUS) test results, highlighting the need for increased genetics education of treating clinicians.2
The current study emphasizes the utility of testing, particularly for those with positive results; over 90% of these patients reported they completed or planned to complete at least one clinical recommendation made by their physician. This included treatment modifications and cascade testing for family members, interventions that can significantly impact outcomes. Furthermore, across all patients, over 90% reported no increase in concern for themselves or their family members post-testing, and many experienced reduced anxiety following testing.
However, the findings also revealed some notable gaps. Only 63% of patients with positive results accurately recalled and understood their testing findings, with an even lower percentage in those with VUS-only results (23%). This disconnect poses a risk to informed decision-making and highlights the need for clearer communication strategies. Additionally, despite being non-actionable, 28% of patients with VUS-only results received follow-up recommendations, and 60% of patients with these results pursued management changes not made by their clinicians.3 These findings suggest that both clinicians and patients may be over-interpreting VUS findings, potentially leading to unnecessary interventions or anxiety. Given that most VUS will eventually be reclassified as benign,4,5 it is imperative that urologists understand the limitations of these results and communicate them appropriately. Collaboration with genetic counselors or the use of standardized educational tools may help mitigate this issue.
As germline testing becomes standard practice, urologists should be equipped to interpret results and guide patients accordingly. Continuing medical education, decision-support tools, and streamlined referral pathways to genetic specialists will be essential. Overall, the PROCLAIM Trial is both a validation and a call to action. Universal germline testing for patients with PCa is feasible, safe, and clinically impactful - but its success depends on how well we communicate results, interpret findings, and support patients in navigating their options. As frontline providers in PCa care, urologists should lead the charge in translating genetic insights into personalized, evidence-based management.
Written by: Neal Shore, MD1 & Sarah M. Nielsen, MS, CGC2 on behalf of PROCLAIM co-investigators
- Carolina Urologic Research Institute, Myrtle Beach, SC
- Labcorp (formerly Invitae Corp.), San Francisco, CA
- Shore, N. et al. Efficacy of National Comprehensive Cancer Network Guidelines in Identifying Pathogenic Germline Variants Among Unselected Patients with Prostate Cancer: The PROCLAIM Trial. European Urology Oncology 6, 477–483 (2023).
- Shore, N. et al. Clinician-reported management recommendations in response to universal germline genetic testing in patients with prostate cancer. J. Urol. 101097JU0000000000004190 (2024).
- Shore, N. D. et al. Using patient-reported outcomes from the PROCLAIM trial to assess the impact of universal germline genetic testing for prostate cancer patients. Prostate Cancer Prostatic Dis. 1–7 (2025).
- Nicolosi, P., Heald, B. & Esplin, E. D. What is a variant of uncertain significance in genetic testing? European Urology Focus 8, 654–656 (2022).
- Chen, E. et al. Rates and Classification of Variants of Uncertain Significance in Hereditary Disease Genetic Testing. JAMA Netw Open 6, e2339571 (2023).