The Prognostic Value of Proclarix in Prostate Cancer Patients Under Active Surveillance: Predicting Transition to Active Treatment and Disease Progression in a Danish Cohort

Background and Objective: Active surveillance (AS) describes the active monitoring of men with low- to intermediate-risk prostate cancer (PCa), before active management (AM) is needed due to disease progression. A substantial proportion of patients require a transition to AM within a few years of diagnosis. Proclarix is a blood-based diagnostic test that predicts clinically significant PCa (csPCa) and the Proclarix risk score has been shown to correlate with tumor aggressiveness. This study aimed to assess whether Proclarix can predict the likelihood of transition from AS to AM and to compare it to PSA density (PSAD). Methods: We retrospectively evaluated the Proclarix risk scores in serum samples from a Danish cohort of 132 men recruited from the PerPros prostate biobank. Most participants had low- to intermediate-risk PCa and were considered eligible for AS at diagnosis. Blood samples were collected before the initial biopsies, and clinical follow-up data were available for every patient for a minimum of 3 and up to 9.5 years. The primary endpoint was the ability of the Proclarix risk score to predict the transition from AS to AM. The secondary endpoint was to assess whether Proclarix could identify patients at risk of progression to csPCa. For both endpoints, PSA density was also included in the analysis for comparison. Results: Overall, 48 of 132 men (36%) transitioned from AS to AM during follow-up. A baseline Proclarix risk score of ≥50% was associated with a 79% estimated cumulative probability of switching to AM (HR = 4.4, 95% CI: 2.3–8.3, p < 0.001), compared to the 58% (HR = 3.1, 95% CI: 1.7–5.7, p < 0.001) for PSAD At the 5-year follow-up, 82% of men with a Proclarix score ≥ 50% and 57% with PSAD ≥ 0.15 ng/mL/cm3 had progressed to AM. Additionally, 67% and 54% of men showed progression to csPCa with, respectively, Proclarix and PSAD at the confirmatory biopsy. In contrast, among men with a Proclarix score < 50%, only 28% progressed to AM and 32% to csPCa, whereas for PSAD < 0.15 ng/mL/cm3, 17% transitioned to AM and 23% progressed to csPCa. Conclusions: The Proclarix risk score may support clinical decision-making in AS by identifying patients at higher risk of progression and informing follow-up intensity. However, the results should be confirmed in a larger prospective study.