| Abstract [eng] |
Significant numbers of prostate cancer (PCa) patients experience tumour upgrading and upstaging in surgical specimens that cause serious problems in timely and proper selection of the treatment strategy. The dissertation aims at evaluating suitability of clinico-pathological characteristics presently used in everyday clinical practice for PCa diagnostics, exploring PCa epigenetic profile and evaluating potential molecular markers (RARβ, RASSF1 and GSTP1) for timely prediction of accurate PCa diagnosis. Upgrading was observed in 27% and upstaging in 20% of PCa patients. Patients undergoing upgrading or upstaging were 1.5 times more likely to have a PSM on radical prostatectomy pathology. Both upgrading and upstaging were associated with increased risk for BCR: 1.8 and 2.1 times, respectively. Mean time to BCR after radical prostatectomy was 2.1 years in upgraded cases and 2.7 years in patients with no upgrading, while mean time to BCR was 1.9 years in upstaged and 2.8 years in non-upstaged cases. Grade and stage increase after RP were associated with inferior MFS rates and ten-year CSS: 89% vs. 98% for upgrading and 87% vs. 98% for upstaging. DNA methylation changes in at least one gene were detected in more than 80% of urine samples. Combination of PSA test with the 3-gene (RARβ, RASSF1 and GSTP1) methylation analysis was a significant predictor of pathological upgrading and upstaging in voided and catheterized urine. |
