Recurrent Prostate cancer remains a major problem, where staging, grading and prostate-specific antigen (PSA) level at the time of surgery are helpful, but still imperfect predictors for recurrence. For this reason, there is an imperative need of additional biomarkers that add to the prediction of the currently used prognostic factors.

We evaluated the extent of promoter methylation of genes previously reported as aberrantly methylated in prostate cancer (PCa) (AIM1, APC, CCND2, GPX3, GSTP1, MCAM, RARβ2, SSBP2 and TIMP3), by quantitative fluorogenic methylation-specific PCR (QMSP) using cancer tissue from a nested case-control study of 452 patients surgically treated for prostate cancer. Recurrence cases and controls were compared and the association between extent of methylation and risk of recurrence was estimated using logistic regression adjusting for prostatectomy age, year, stage, grade, surgical margins, and pre-prostatectomy PSA concentration. All statistical tests were two-sided, and p<0.05 was considered to be statistically significant.

GSTP1 methylation extent was higher in recurrence cases than in controls (p = 0.01), especially in patients with early disease (i.e., organ-confined or limited extra-prostatic extension) (p = 0.001). After multivariable adjustment, having at or above the median extent of GSTP1 promoter methylation was associated with an increased risk of recurrence, including in men with early disease (both p = 0.05).

Greater GSTP1 promoter methylation in cancer tissue was independently associated with risk of recurrence in patient with early prostate cancer, suggesting its testing as a potential tissue-based recurrence marker.