PURPOSE: We developed and externally-validated a non-DRE urine test to inform whether biopsy is necessary in patients undergoing active surveillance (AS). Performance and clinical consequences of testing were directly compared to multiparametric magnetic resonance imaging (mpMRI). MATERIALS AND METHODS: Biomarker models (MyProstateScore 2.0 - Active Surveillance MPS2-AS) were derived to predict upgrading to Grade Group (GG)≥3 and GG≥2 and externally validated across 11 practices. Urine was prospectively collected, and patients underwent ≥12-core systematic biopsy (SBx) plus targeted biopsy (TBx) of PI-RADS≥3 lesions. Diagnostic performance and clinical consequences of urinary testing to determine the need for biopsy were compared to mpMRI. RESULTS: The validation cohort included 330 patients with GG1 cancer scheduled for AS biopsy. Overall, 280 (85%) patients had pre-biopsy mpMRI, of which 130 (46%) were PI-RADS 1-2, 42 (15%) were PI-RADS 3, and 108 (39%) were PI-RADS 4-5. On biopsy, 31 (9.4%) patients upgraded to GG≥3 and 123 (37%) to GG≥2. MPS2-AS provided higher AUC than mpMRI for upgrading to both GG≥3 (0.82 vs. 0.73) and GG≥2 (0.74 vs. 0.64). Clinically, pre-biopsy MPS2-AS would have avoided 64% of unnecessary biopsies while failing to detect only 3.2% of GG≥3 upgrades. By contrast, use of PI-RADS≥3 would have failed to detect 18% of GG≥3 upgrades and avoided fewer unnecessary biopsies (50%). Performance of MPS2-AS was consistent across clinically-pertinent subgroups (confirmatory and surveillance biopsy, Black and non-Black patients). CONCLUSIONS: In a multisite AS population, urinary MPS2-AS provided highly accurate and actionable testing for GG≥3 and GG≥2 upgrading, meaningfully outperforming mpMRI on direct comparison. These findings suggest that non-invasive monitoring with MPS2-AS could reduce the need for scheduled biopsies and serial mpMRI.
Tosoian et al. (Tue,) studied this question.