Abstract
BackgroundSignificant numbers of prostate cancer (PCa) patients experience tumour upstaging and upgrading in surgical specimens that cause serious problems in timely and proper selection of the treatment strategy. This study was aimed at the evaluation of a set of established epigenetic biomarkers as a noninvasive tool for more accurate PCa categorization before radical prostatectomy (RP).MethodsQuantitative methylation-specific PCR was applied for the methylation analysis of RARB, RASSF1, and GSTP1 in 514 preoperatively collected voided or catheterized urine samples from the single-centre cohort of 1056 treatment-naïve PCa patients who underwent RP. The rates of biopsy upgrading and upstaging were analysed in the whole cohort.ResultsPathological examination of RP specimens revealed Gleason score upgrading in 27.2% and upstaging in 20.3% of the patients with a total misclassification rate of 39.0%. DNA methylation changes in at least one gene were detected in more than 80% of urine samples. Combination of the PSA test with the three-gene methylation analysis in urine was a significant predictor of pathological upstaging and upgrading (P < 0.050), however, with limited increase in overall accuracy. The PSA test or each gene alone was not informative enough.ConclusionsThe urinary DNA methylation assay in combination with serum PSA may predict tumour stage or grade migration post-RP aiding in improved individual risk assessment and appropriate treatment selection. Clinical utility of these biomarkers should be proven in larger multi-centre studies.
Highlights
Significant numbers of prostate cancer (PCa) patients experience tumour upstaging and upgrading in surgical specimens that cause serious problems in timely and proper selection of the treatment strategy
86.4% (241/ 279) of the patients were initially diagnosed with Clinical International Society of Urological Pathology (ISUP) grade group (cGG) 1 disease, the majority of whom (86.3%, 208/241) were upgraded to Pathological ISUP grade group (pGG) 2 disease (Fig. 1a)
Histopathological examination of the whole prostate gland after radical prostatectomy (RP) revealed that 23.9% (245/1025) of the patients were assigned to a higher postoperative PCa risk group than clinically suspected, of whom 69.8% (N = 171) had been preoperatively diagnosed with low-risk PCa
Summary
Significant numbers of prostate cancer (PCa) patients experience tumour upstaging and upgrading in surgical specimens that cause serious problems in timely and proper selection of the treatment strategy. Prostate cancer (PCa) treatment selection mostly depends on tumour biopsy-based Gleason score (GS) and clinical tumour stage (cT). The proper treatment of the patients, whose cancer is later upgraded and/or upstaged, might be delayed resulting in irreversible consequences, while overtreatment is a serious concern for men whose biopsies are downgraded. Identification of cancer-associated genetic and epigenetic alterations in body fluids, containing molecular information from all tumour foci and reflecting PCa heterogeneity, may provide valuable supplementary data. PCa-specific methylated DNA is detectable in liquid biopsy samples, such as urine or blood, and can provide additional information beyond the limitations of standard prostate biopsy [10]
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