The dissertation is devoted to improving the quality of diagnosis and treatment of patients with prostate cancer by creating panels of biomarkers for screening-diagnosis and verification, designed for both long-term use and adapted to real conditions, based on theoretically determined critical values of tests with reasonable prognostic properties, as well as by improving endoscopic radical prostatectomy.
The work has two interrelated parts - clinical and epidemiological. It was performed at the Institute of Urology of the National Academy of Medical Sciences of Ukraine, the material bases of the Institute of Molecular Biology and Genetics of the National Academy of Sciences of Ukraine and the National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine were involved.
According to a 15-year analysis of official statistics (forms №47-healthy, 7, 35), systemic modern problematic issues of specialized care for patients with PC were identified. The unfavorable situation in Ukraine and its administrative territories was manifested by an increase in the incidence and prevalence of pathology at different rates over the years and regions, a particularity - an increase in morbidity (41.6%) and a slowdown in 2014-2018. As a result, their levels were 47.3 and 214.4 per 100 thousand people. At the same time, there was an increase (by 22.2%) in the diagnosis of the disease in its IV stage (up to 22.4%) and a decrease in I - II (by 4.3%) to 42.6%, as well as an increase in mortality from 17.7 up to 21.34 (per 100 thousand) against the background of a decrease in patients (by 16.2%) identified during professional examinations and a larger number of those who receive special treatment annually (by 22.1%), including surgery at 4.0%). The stratification of regions of Ukraine according to five gradations of the level of problems has been objectified.
The clinical component was based on 333 observations, which are divided into representative groups by number to solve problems. Biomarkers were processed according to the standard examination of 246 patients, for whom it was verified that 107 had PC, 71 had BPH, and 68 were relatively healthy. The properties of known common and limited in practice biomarkers were further investigated. The biomaterial of 33 patients with PC, BPH and 4 conditionally healthy was used to study genetic promising markers. 106 patients with PC were involved in the development of advanced technology of endoscopic radical prostate ectomy The imperfection of the existing complex of examination of patients for the purpose of differential diagnosis of PC is proved and the expediency of its expansion by forms derived from PSA (total PSA, % free PSA, [-2] about PSA, % [-2] about PSA, prostate health index) was substantiated, of which the latter stands out for its accuracy, sensitivity and specificity. A direct relationship between the value of biomarkers and their diagnostic properties and their objectification on this basis was proved. The critical values of PC biomarkers were substantiated and their diagnostic accuracy was established. It was found that the expression of the PCA3 gene in the prostatic tissue during the development of carcinogenesis is increased 100 times. There was traced a direct dependence of its level in post-massage urine on the aggressiveness of the cancer process, the number of tumors and their volume. Three perspective panels of different gene / locus composition and action vector were proposed. The logistic model of two new biomarkers (PCA3 and prostate health index) was substantiated, which significantly (by 31%) exceeded the prognostic capacity of the traditional panel (total PSA, % free PSA, PSAd). A modified method of urethrovesical anastomosis formation in endoscopic RPE under conditions of gland volume - 80 - 150 cm3 is proposed, the essence of which is to improve the procedure of diastase liquidation between the bladder neck and membranous urethra and a new approach to creating an anterior sling; its advantage is in the early recovery of the continent: on the 3rd day in 23.2% of cases against 16.0%, after 1 month - 44.1% against 36.9%, after 3 months - in 83.3% against 66.6%, after 12 months all achieved a functional effect, while the standard in 87.8% of cases, and the method does not affect the frequency of biochemical recurrence.
