MPS2-AS outperforms mpMRI for prostate cancer upgrading during active surveillance

A noninvasive urine-based assay, MyProstateScore 2.0–Active Surveillance (MPS2-AS), demonstrated improved diagnostic performance compared with multiparametric MRI (mpMRI) for detecting disease upgrading in men with Grade Group (GG) 1 prostate cancer undergoing active surveillance, according to a multisite external validation study published in The Journal of Urology.¹

The validated performance of MPS2-AS introduces a potential noninvasive adjunct that could improve risk stratification and reduce unnecessary biopsies in this population.

“With aims of reducing the burden of testing for patients on active surveillance, MRI has become widely used for monitoring, despite evidence in this setting that it lacks the accuracy needed to rule out higher-grade cancers,” commented lead author Jeffrey Tosoian, MD, MPH, of Vanderbilt University Medical Center, in correspondence with Urology Times^®. “Our findings again showed that active surveillance based on MRI would have missed far too many high-grade cancers—around 20% of extreme upgrades (to GG3 [or higher] cancer) and 40% of upgrades to GG2 [or higher] cancer. Meanwhile, MPS2-AS detected 97% of GG3 [or higher] upgrades and 95% of GG2 [or higher] upgrades, while allowing patients to avoid one-third to two-thirds of unnecessary biopsies (those that would not have detected upgrading).”

Trial overview

The externally validated study evaluated the performance of MPS2-AS in 330 men with GG1 prostate cancer scheduled for active surveillance biopsy across 11 clinical sites. Urine samples were prospectively collected without digital rectal examination (DRE), and all patients underwent at least 12 core systematic biopsies with targeted biopsy of suspicious lesions (PI-RADS ≥3) identified on mpMRI.

The primary end points included detection of upgrading to GG3 or higher and GG2 or higher disease. Among the 280 patients (85%) who underwent pre-biopsy mpMRI, 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% of total cohort) patients were upgraded to GG3 or higher, and 123 (37% of total cohort) were upgraded to GG2 or higher.

MPS2-AS demonstrated superior discrimination compared with mpMRI, with an area under the curve of 0.82 vs 0.73 for GG3 or higher upgrading and 0.74 vs 0.64 for GG2 or higher upgrading.

Clinically, use of the assay could have avoided up to 64% of unnecessary biopsies, while missing 3.2% of GG3 or higher upgrades. By comparison, reliance on mpMRI (PI-RADS ≥3 threshold) would have missed 18% of GG3 or higher upgrades and avoided fewer unnecessary biopsies (50%). Sensitivity for detecting GG3 or higher upgrading was 97% with a negative predictive value (NPV) of 99%, while sensitivity for GG2 or higher disease was 95% with an NPV of 92%.

MPS2-AS performed consistently across clinically relevant subgroups, including confirmatory vs surveillance biopsy and Black vs non-Black patients.

Tosoian added, “These findings suggest that we may be able to shift to a non-invasive, urine-based approach to active surveillance without compromising the accuracy provided by frequent repeat biopsies.”

Diagnostic background behind MyProstateScore 2.0

MPS2-AS builds on the previously developed MyProstateScore 2.0 platform, a urine-based assay designed to inform initial biopsy decisions in men with suspected prostate cancer. The test evaluates 18 unique gene transcripts associated with prostate cancer biology to generate a personalized risk score for clinically significant disease.²

Related: Cameron Britton, MD, discusses clinical outcomes with the MyProstateScore 2.0 assay

Unlike earlier urine assays, MPS2-AS is specifically designed for patients already diagnosed with GG1 disease and undergoing surveillance. The assay does not require DRE prior to urine collection and is intended for flexible use in either at-home or office-based settings, potentially improving accessibility and adherence.

According to the company Lynx Dx, it plans to make MPS2-AS available with Medicare coverage.

"Active surveillance works best when clinicians can reliably identify the patients who need a biopsy while sparing those who do not," said Spencer Heaton, MD, MBA, CMO at Lynx Dx, in a news release on the findings.³ "MPS2-AS is a promising non-invasive tool that helps reduce the burden of repeat biopsies, personalize monitoring, and support more confident decision-making for men living with low-risk prostate cancer."

REFERENCES

1. Tosoian JJ, Meyers JI, Moore B, et al. Non-invasive urine test predicts grade group upgrading in patients on active surveillance for prostate cancer: multisite validation and comparison with MRI. J Urol. Published online April 28, 2026. doi:10.1097/JU.0000000000005095

2. Tosoian JJ, Zhang Y, Meyers JI, et al. Clinical validation of MyProstateScore 2.0 testing using first-catch, non–digital rectal examination urine. J Urol. 2025;213(5):581-589. doi:10.1097/JU.0000000000004421

3. New Lynx Dx urine test outperforms MRI in identifying prostate cancer upgrading during active surveillance. News release. Lynx Dx. May 5, 2026. Accessed May 6, 2026. https://www.prnewswire.com/news-releases/new-lynx-dx-urine-test-outperforms-mri-in-identifying-prostate-cancer-upgrading-during-active-surveillance-302762747.html