Design: multisite external validation with direct within-cohort comparison against multiparametric magnetic resonance imaging
Population: 330 men with grade group 1 prostate cancer scheduled for active surveillance biopsy across 11 practices
Primary outcome: detection of upgrading to grade group 3 or higher and grade group 2 or higher
Effect: area under the curve 0.82 versus 0.73 for grade group 3 or higher; urine testing avoided 64% of biopsies missing 3.2% of upgrades, against PI-RADS 3 or higher missing 18%

Three hundred and thirty men with grade group 1 prostate cancer scheduled for an active surveillance biopsy were tested with a urinary biomarker panel, MyProstateScore 2.0-Active Surveillance, derived and then externally validated across 11 practices. All had at least 12-core systematic biopsy plus targeted biopsy of any PI-RADS 3 or higher lesion, and 280 (85%) had prebiopsy multiparametric magnetic resonance imaging — giving a direct comparison rather than a historical one. The test requires no digital rectal examination.

On biopsy, 31 (9.4%) upgraded to grade group 3 or higher and 123 (37%) to grade group 2 or higher. The urine test discriminated better than magnetic resonance imaging on both: area under the curve 0.82 against 0.73 for grade group 3 or higher, and 0.74 against 0.64 for grade group 2 or higher. Translated into consequences, using the urine test to decide on biopsy would have avoided 64% of unnecessary biopsies while missing 3.2% of grade group 3 or higher upgrades and 4.9% of grade group 2 or higher upgrades. Using PI-RADS 3 or higher as the trigger would have missed 18% of grade group 3 and 35% of grade group 2 upgrades while avoiding fewer biopsies (50%). Performance held across confirmatory and surveillance biopsies and in Black and non-Black patients.

That is a substantial result. The standard of care on active surveillance — serial magnetic resonance imaging plus scheduled biopsy — is expensive, unpleasant and, on these figures, less accurate than a urine sample. Missing 18% of significant upgrades is what current practice does when imaging is used as the gate.

The constraints are real. This is one validation of one commercial assay, the test is not available in India, and no trial has yet shown that a surveillance programme run on urine testing produces the same long-term outcomes. But the comparison is honest and direct, and it should change what is regarded as the benchmark for any biopsy-avoidance strategy.

Stop treating PI-RADS 1 to 2 as sufficient reassurance to skip a surveillance biopsy; it missed 18% of grade group 3 upgrades here
Where the assay is available, use it to select for biopsy rather than as an add-on to imaging
Keep systematic plus targeted biopsy as the reference when a biopsy is done
Ask for the numbers that matter when a biopsy-avoidance test is offered: biopsies avoided, and significant upgrades missed
Do not extrapolate to initial diagnosis; this was validated in men already on surveillance with grade group 1 disease

Don't overread it

One validation of one commercial assay, with no outcome data showing that a surveillance programme run this way is as safe over years.

The statistics, in plain English

Areas under the curve of 0.82 against 0.73 represent a meaningful gain in discrimination, but the numbers that should drive practice are the consequence figures: 64% of biopsies avoided at the cost of 3.2% of grade group 3 upgrades missed. Those depend entirely on where the threshold is set, and a threshold chosen in the same data will look better than it will in the next cohort. The 31 grade group 3 upgrades are a small number on which to build the headline comparison. The most robust part is the magnetic resonance imaging arm, because PI-RADS 3 or higher is a fixed, externally defined threshold and it performed poorly.