IsoPSA in prostate cancer: A systematic review of diagnostic, prognostic and economic implications.

Abstract

e17166 Background: Prostate cancer (PCa) is the most commonly diagnosed cancer in men and 2nd leading cause of cancer-related deaths. Traditional Prostate-specific antigen (PSA)-based markers are tissue but not cancer specific. While they are widely used, they lack specificity in distinguishing clinically significant PCa (csPCa) from more indolent forms, leading to overdiagnosis and overtreatment. Isoform-based-PSA (IsoPSA) assay can improve diagnostic accuracy by detecting cancer-specific structural PSA isoforms, tentatively interrogating the entire spectrum of structural changes in PSA. This review aims to consolidate existing evidence on IsoPSA’s diagnostic, prognostic, and economic impact to clarify its role as a novel biomarker in advancing precision PCa management. Methods: PubMed and Google Scholar databases were searched for studies between 2025 and 2015. A total of 7 studies with 3,125 participants were included in the analysis. The studies comprised a mix of retrospective and prospective cohorts, cost analyses, and secondary analyses. Analysis was focused on assessing and synthesizing metrics relating to diagnostic accuracy, overall performance(AUC), sensitivity, specificity, negative predictive value, positive predictive value, prognostic implications, particularly the future risk of csPCa and the economic impact in terms of cost saving and unnecessary biopsy reduction. Results: IsoPSA outperformed traditional and free PSA in detecting clinically significant PCa and reducing unnecessary biopsies. AUC values ranged from 0.77 to 0.81 across studies for detecting high-grade PCa, showing robust diagnostic accuracy. It reduced unnecessary biopsies by 42–48%, with MRI-guided biopsy further improving AUC to 0.83. Cost analyses indicated significant savings, reducing biopsy frequency by up to 34% in certain groups and saving up to $53,300 per 100 men. IsoPSA reliably detected clinically significant prostate cancer (csPCA), with a low csPCa diagnosis rate (4.3%) among patients with indices ≤6, with higher indices strongly associated with increased csPCa risk. Performance was unaffected by 5-ARIs or α-blockers, supporting utility across diverse patient groups. Conclusions: IsoPSA, a cancer specific structure-based biomarker, which reflects cancer biology outperforms traditional PSA tests in detecting csPCA and reducing unnecessary biopsies, by using a structure-based rather than concentration based approach. It is unaffected by medications like 5-ARIs and α-blockers. Integration of IsoPSA with imaging guided biopsy techniques can refine diagnostic paradigms, highlighting its potential in enhancing precision PCa management and optimizing patient outcomes. Further large scale prospective studies are imperative to assess refinement in clinical utility by reducing overdiagnosis and overtreatment of non lethal forms of PCa.