GSTP1 promoter hypermethylation in prostate cancer detection: current evidence, clinical positioning, and translational gaps

GSTP1 promoter hypermethylation is one of the most consistently documented molecular alterations in prostate cancer, with high prevalence in malignant tissue and a well-established relationship with transcriptional silencing. However, despite more than two decades of biological and diagnostic investigation, GSTP1-based testing has not acquired a clearly defined stand-alone role in contemporary prostate cancer detection. This narrative review examines why extensive biological evidence has not translated into routine clinical use and where, if anywhere, GSTP1 testing might provide meaningful value within current diagnostic pathways. Evidence from prostate tissue, urine and circulating cell-free DNA is considered alongside the effects of biospecimen selection, preanalytical handling, CpG target selection, assay design and interpretation thresholds. Tissue demonstrates the most reproducible signal and has achieved partial clinical translation through multiplex testing such as ConfirmMDx, whereas urinary and blood-based approaches remain investigational. Recent urinary findings, including in men with moderately elevated PSA, are promising but remain preliminary and have not established incremental value beyond contemporary risk assessment, biomarkers and multiparametric MRI. The translational priority is therefore not to demonstrate again that GSTP1 detects prostate cancer, but to determine whether a standardised assay provides reproducible, nonredundant and clinically actionable information at a defined decision point. Future development should prioritise clearly specified target populations, analytically validated assay configurations, clinically significant prostate cancer as the relevant endpoint, and prospective evaluation against contemporary diagnostic pathways.