Noninvasive Urine Test Predicts Grade Group Upgrading in Patients on Active Surveillance for Prostate Cancer:...

We developed and externally validated a nondigital rectal examination urine test to inform whether biopsy is necessary in patients undergoing active surveillance (AS). Performance and clinical consequences of testing were directly compared with multiparametric MRI (mpMRI).

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 plus targeted biopsy of Prostate Imaging Reporting and Data System (PI-RADS) ≥ 3 lesions. Diagnostic performance and clinical consequences of urinary testing to determine the need for biopsy were compared with mpMRI.

The validation cohort included 330 patients with GG1 cancer scheduled for AS biopsy. Overall, 280 (85%) patients had prebiopsy mpMRI, of which 130 (46%) were PI-RADS 1 to 2, 42 (15%) were PI-RADS 3, and 108 (39%) were PI-RADS 4 to 5. On biopsy, 31 (9.4%) patients upgraded to GG ≥ 3 and 123 (37%) to GG ≥ 2. MPS2-AS provided higher area under the receiver operating characteristic curve than mpMRI for upgrading to both GG ≥ 3 (0.82 vs 0.73) and GG ≥ 2 (0.74 vs 0.64). Clinically, prebiopsy MPS2-AS would have avoided 64% of unnecessary biopsies while failing to detect only 3.2% of GG ≥ 3 upgrades and 4.9% of GG ≥ 2 upgrades. By contrast, the use of PI-RADS ≥ 3 would have failed to detect 18% of GG ≥ 3 upgrades, 35% of GG ≥ 2 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).

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 noninvasive monitoring with MPS2-AS could reduce the need for scheduled biopsies and serial mpMRI.