Optimizing Prostate Cancer Diagnostics: Can Biomarkers Decrease the Burden of Over-Investigation?

The foundation of current prostate cancer diagnostics still remains the interpretation of total PSA (tPSA) results, but it is an imperfect test due to its low specificity and diagnostic ambiguities in patients within the "gray zone," meaning patients with a result of (2.0/4.0–10.0 ng/mL). This fact leads to many cases of "overdiagnosis" and an excess of unnecessarily performed biopsies. This article summarizes the diagnostic value of blood-based biomarkers and tests (PHI, 4Kscore, Stockholm3) as well as urine-based ones (SelectMDx and ExoDx). These tests achieve high AUC values (0.76–0.88) and a high negative predictive value (up to 98%) in detecting clinically significant prostate cancer (csPCa, GG ≥ 2), underscoring their advantage over traditional methods. Combining them with multiparametric MRI allows for a 30–65% reduction in unnecessary biopsies while maintaining high oncological safety for the patient. Despite promising results, the high costs of individual tests, lack of reimbursement, and absence of full standardization in international urological guidelines remain a continuous challenge and a hurdle to their introduction into daily practice.