Prospective validation of a urine-based proteomics test for predicting clinically significant prostate cancer in biopsy-naïve patients

Prostate cancer is a major health burden, while existing diagnostic approaches are limited by overdiagnosis that leads to unnecessary biopsies, and by underdetection of clinically significant prostate cancer (csPCa). A multicenter study in Spain and Austria was carried out to prospectively validate a urine-based 19-biomarker model (19-BM) using capillary electrophoresis-mass spectrometry (CE-MS) for predicting csPCa in patients at risk. One hundred sixty-one biopsy-naïve patients at risk for csPCa underwent pre-biopsy CE-MS analysis in urine, multiparametric magnetic resonance imaging (mpMRI), and biopsy. The 19-BM performance was assessed in comparison with PSA, the European Randomized Study of Screening for Prostate Cancer (ERSPC), and mpMRI. One hundred patients receiving radical prostatectomy were evaluated to investigate the correlation of the 19-BM scores with prostatectomy pathology. The 19-BM scores achieve an AUC of 0.79, outperforming PSA (AUC 0.54; p<0.0001), ERSPC (AUC 0.63; p=0.0108), PSAD (AUC 0.61; p=0.0021), and mpMRI (AUC 0.65l; p=0.0069). In patients with low PI-RADS scores, 19-BM showed a sensitivity of 75% and specificity of 90%. Prospective validation of a previous nomogram combining 19-BM with mpMRI yielded an AUC 0f 0.82, with specificity of 90% and sensitivity of 64%. The authors conclude that the 19-BM demonstrated robust performance in predicting csPCa, as a valuable complement to current diagnostic methods. potentially reducing the need for invasive procedures.