Genomic Prostate Score Identifies Biologically Low-Risk Disease

A retrospectively evaluated 17-gene Genomic Prostate Score (GPS mdx) test identified a highly prevalent subgroup of patients with clinically higher-risk prostate cancer but biologically indolent disease who achieved favorable 6-year oncological outcomes across active surveillance, radical prostatectomy (RP), and radiotherapy, supporting the feasibility of future trials evaluating genomics-guided management de-escalation, according to findings from the Oxford GPS-ProMPT trial published in European Urology Oncology.¹

The Oxford GPS-ProMPT study, led by investigators at the Nuffield Department of Surgical Sciences at the University of Oxford, assessed GPS in 409 patients with biopsy-proven prostate cancer managed with active surveillance (n = 103), RP (n = 155), or radiotherapy with androgen deprivation therapy (ADT; n = 99 localized; n = 52 locally advanced), with a median follow-up of at least 6 years across all sub-cohorts. Pathology teams were blinded to clinical outcomes during GPS assessment, and all clinical, specimen, and genomic data were quality-controlled and locked before statistical analysis.

GPS successfully stratified patients by risk of adverse oncological outcomes in all cohorts. A GPS of 25 or greater significantly increased the risk of active surveillance failure (HR, 4.9; 95% CI, 1.3-18.8; P = .03), while a GPS of 40 or greater predicted all metastatic and high-risk biochemical recurrence events per European Association of Urology criteria in the RP (P <.001) and the radiotherapy with ADT (P = .02) cohorts. In the exploratory locally advanced disease cohort, a GPS of 55 or greater correlated with significantly higher risk of treatment failure (HR, 7.1; 95% CI, 1.8–28.4; P = .03).

Investigators identified a prevalent "discordant low-risk" phenotype in patients with adverse clinical features per NCCN risk categories but favorable GPS results. Among patients with low GPS scores, which comprised 58% of the total study population, those with discordant low-risk status—representing an NCCN score of at least 2 but low GPS—made up 46% of patients undergoing active surveillance with an NCCN score of at least 2, 57% of those undergoing RP with an NCCN score of at least 3, 36% of those with an NCCN score of at least 4 undergoing radiotherapy, and 48% of patients with locally advanced disease and an NCCN score of 5.

Six-year event-free survival (EFS) rates in these patients were 88% with active surveillance, 100% with both RP and radiotherapy, and 95% in the locally advanced cohort—comparable with the 100% 6-year EFS rate observed in all concordant low-risk patients, defined as those with both low GPS and lower NCCN risk category.

"The ProMPT findings demonstrate that patients with favorable GPS mdx scores achieved excellent long-term outcomes—including 92% freedom-from-failure at 6 years in active surveillance and up to 100% in surgery and radiotherapy cohorts—even among those with adverse clinical risk factors,” lead study investigator Nikita Sushentsev, PhD, Academic Clinical Fellow in Radiology at Cambridge University Hospitals NHS Foundation of Trust, stated in a news release from the developer, Mdxhealth.¹ “This suggests GPS mdx can identify favorable tumor biology that traditional risk stratification alone would miss, with meaningful implications for how we counsel patients facing treatment decisions."

The study investigators noted that while these retrospective data with a limited number of events do not support immediate changes to clinical practice, the high prevalence and favorable safety profile of the discordant low-risk phenotype provide preliminary evidence that support future trials of genomics-guided management de-escalation. These findings also establish the scientific foundation for the GPS-ProtecT study, a planned randomized controlled trial that will validate GPS prospectively in the landmark UK ProtecT trial (NCT02044172), the world's largest randomized trial of treatment effectiveness in localized prostate cancer.³

References

1. Sushentsev N, Colling R, Teague R, et al. Genomic Prostate Score for identifying biologically low-risk disease in patients with prostate cancer undergoing active surveillance, surgery, or radiotherapy. Eur Urol Oncol. Published June 25, 2026. doi:10.1016/j.euo.2026.06.008
2. Mdxhealth announces peer-reviewed publication of Oxford GPS-ProMPT study in European Urology Oncology, establishing scientific foundation for the landmark GPS-ProtecT randomized controlled trial. News release. Mdxhealth. June 29, 2026. Accessed June 29, 2026. https://tinyurl.com/sn8dp3t4
3. Prostate testing for cancer and treatment (ProtecT). ClinicalTrials.gov. Updated November 14, 2022. Accessed June 29, 2026. https://tinyurl.com/44225bm7