GPS-ProMPT: Molecular Profiling Identifies Overtreated Prostate Cancer Subgroup

A retrospective analysis from the Oxford GPS-ProMPT study provides further evidence that genomic profiling can reveal which prostate cancers are truly aggressive and which are not, even when clinical features suggest otherwise. The study evaluated the 17-gene Genomic Prostate Score (GPS mdx) in 409 patients managed with active surveillance, radical prostatectomy, or radiotherapy with androgen deprivation therapy, with a median follow-up of at least six years.

GPS consistently predicted oncological outcomes across all treatment groups.A score of 25 or higher was associated with a significantly increased risk of failure during active surveillance, while scores of 40 or higher identified all metastatic and high-risk biochemical recurrence events in both surgical and radiotherapy cohorts. In locally advanced disease, scores above 55 were linked to a markedly higher risk of treatment failure.

The most relevant finding was the identification of a large subgroup of patients with discordant risk: clinically higher-risk disease but low GPS. This group represented nearly half of patients within higher NCCN categories. Despite unfavorable clinical features, outcomes were excellent. Six-year event-free survival reached 88% with active surveillance and 100% with both surgery and radiotherapy, closely matching outcomes seen in conventionally low-risk patients.

These results suggest that tumor biology, as captured by genomic testing, may be more informative than clinical risk alone. A significant proportion of patients currently classified as intermediate or high risk could potentially be managed with less aggressive approaches.

However, the data are retrospective and based on a limited number of events, so they do not support immediate changes to clinical practice. Ongoing prospective validation, including the planned GPS-ProtecT trial, will be necessary to determine whether genomics-guided treatment de-escalation can be safely implemented.

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