The Urine Test That Might Finally Spare Men the Surveillance Biopsy

A multisite validation study published in The Journal of Urology shows that MPS2-AS - a urine-based test - outperformed mpMRI for detecting grade group upgrading in men on active surveillance for low-risk prostate cancer. The headline number: a 99% negative predictive value for high-grade disease, and the potential to avoid 64% of unnecessary biopsies without missing the men who need treatment.

That 99% NPV is doing a lot of work. If a test is negative, there is only a 1% chance of high-grade cancer on biopsy. For most patients, that is a defensible threshold for forgoing the procedure.

What Active Surveillance Actually Requires

The premise of active surveillance is sound: most Grade Group 1 prostate cancers will never cause harm, and treating them all exposes men to incontinence, erectile dysfunction, and radiation side effects for no benefit. So we watch instead. The problem is that “watching” currently means a repeat biopsy every two to three years, because PSA and MRI alone aren’t reliable enough to tell you which men are silently upgrading to higher-grade disease.

Most surveillance biopsies come back showing no upgrading. The man had another procedure, another anaesthetic, another course of antibiotics, and another few weeks of worry - for the same result. The question the field has been trying to answer for years is: can we use a non-invasive test to identify the men who definitely don’t need a biopsy this cycle, and just biopsy the ones who do?

The MPS2-AS Numbers

The study included over 300 patients on active surveillance for Grade Group 1 prostate cancer. MPS2-AS was validated against mpMRI across multiple centres.

For predicting Grade Group 3 or higher upgrading:

• MPS2-AS sensitivity: 97%. PI-RADS 3 or higher: 82%. PI-RADS 4 or higher: 79%.
• MPS2-AS NPV: 99%. PI-RADS 3 or higher: 96%. PI-RADS 4 or higher: 97%.

For predicting Grade Group 2 or higher upgrading:

• MPS2-AS sensitivity: 95%. PI-RADS 3 or higher: 65%. PI-RADS 4 or higher: 55%.
• MPS2-AS NPV: 92%. PI-RADS 3 or higher: 71%. PI-RADS 4 or higher: 72%.

The sensitivity gap against MRI is the key finding. The NPV numbers are somewhat comparable at the high-grade end - but MPS2-AS is catching significantly more Grade Group 2 upgrades than MRI, which matters because GG2 is the threshold where treatment conversations start.

What We Don’t Know Yet

This is a validation study, not a randomised trial. We have diagnostic performance data, but we don’t yet know whether using MPS2-AS to guide biopsy decisions actually changes patient outcomes - specifically, whether the men who avoid biopsy on a negative test don’t later present with missed high-grade disease.

The 1% miss rate for GG3 is reassuring, but 1% across thousands of surveillance patients is still real numbers. The consent conversation for a negative-test patient who goes biopsy-free for a cycle needs to include that residual risk honestly.

We also don’t have cost-effectiveness data, and the test isn’t routinely available in UK practice yet. Implementation at scale requires reimbursement, lab infrastructure, and integration into existing surveillance pathways that are already anchored around NICE guidance and mpMRI.

Why It’s Worth Following

Active surveillance is one of the genuine success stories of modern uro-oncology - we are unambiguously overtreating less than we were. But the surveillance biopsy burden remains a real problem for patients and for capacity. A test that could personalise the biopsy interval - spare the low-risk men and flag the ones actually upgrading - would change the pathway meaningfully.

MPS2-AS has the best performance data of any non-invasive test in this space so far. The GG2+ sensitivity of 95% versus 55-65% for MRI alone is the number that distinguishes it. Whether that holds up in prospective implementation studies, and whether it can be integrated into UK surveillance protocols, is what comes next.