INFLUENCE OF ADDING ZINC ARGINYLE-GLYCINATE TO IMPROVE EFFICACY OF BIOREGULATORY PEPTIDES OF THE PROSTATE GLAND IN TREATMENT OF PATIENTS WITH IMPAIRED SPERM PARAMETERS.

The drug Prostatilen® AC, rectal suppositories were developed on the basis of the previously registered medicine containing bioregulatory peptides of the prostate gland - Prostatilen® rectal suppositories, 3 mg, from whom it differs by the addition of аctive pharmaceutical ingredient zinc arginyle-glycinate dihydrochloride (ZAG). The aim of this study was to analyze the positive effect of adding ZAG to the drug in patients with impaired spermatogenesis. A total of 98 men aged 25-45 years (an average of 35.2±4.3 years) with a verified diagnosis of chronic abacterial prostatitis and related reproductive dysfunctions in the phase III, randomized, multicenter, open-label clinical trial was examined. The duration of participation of patients in the study was 14-16 days, the screening period was 2-3 days, the duration of therapy was 10 days, and the final examination was 2-3 days. A study group (n=49) received therapy with Prostatilen AC once daily, a control group (n=49) had Prostatilen once daily. All patients underwent conventional semen analysis before and after treatment. The obtained parameters were compared. During the analysis of the average statistical data in the comparison groups, it was found that treatment with Prostatilen AC leads to an increase in the total population of motile spermatozoa (cells A + B + C) by 14.3%, and the reference drug Prostatilen contributes to an increase in this indicant by 4.1% compared with the results of a screening examination with significantly higher efficiency in increasing the relative count of spermatozoa with a fast progressive motility (After therapy Prostatilen/Prostatilen AC p=0.0004). Prostatilen AC showed significantly higher efficiency in terms of increasing the count of normal forms of spermatozoa in the ejaculate than the reference drug Prostatilen (After therapy Prostatilen/Prostatilen AC p=0.0118). In patients who received the drug Prostatilen AC the number of abnormal forms of spermatozoa decreased by 12.4% (After therapy - 55.57%), and in the comparison group (drug Prostatilen) by 6.5% (After therapy - 58.90%) with significant decrease in forms of abnormal spermatozoa with head, acrosome, or neck pathology for Prostatilen AC compared to control. Prostatilen AC compared to Prostatilen had a statistically significant and clinically significantly superior efficacy in relation to initially impaired sperm parameters (improve of sperm motility, restoration of morphologically normal sperm, decrease in forms of abnormal spermatozoa with head, acrosome or neck pathology). This drug could be recommended to use in the treatment of patients in whom chronic prostatitis occurs with concomitant disorders of sexual and reproductive functions.

[ROLE OF KINETIC PERFORMANCE OF PSA IN SELECTION OF THE PATIENTS FOR CONDUCTION OF 11C-CHOLINE PET/CT AIMED TO REVEAL LOCAL RECURRENCES OF PROSTATE CANCER].

Given study was aimed to research a role of kinetic performance of PSA in selection of the patients for conduction 11C-choline PET/CT in order to reveal local recurrences in patient with prostate cancer after radiation therapy (RT) and radical prostatectomy (RP). The study included 185 patients with histologically distinctive prostate cancer and biochemical signs of tumor recurrence after RP (61 patients) or RT (124 patients). All the patients were examined using 11C-choline PET/CT in order to detect local relapses. Calculation of growth rate of the PSA level and PSA doubling time were made. According to results of 11C-choline PET/CT, recurrences of prostate cancer were detected in 124 out of 185 (65%). There were 22 patients out of 61 (36%) after RP and there were 102 patients out of 124 (82%) after RT. It was stated a correlation between PSA rates, growth rate of PSA level and presence or absence of relapse according to PET/CT results. PSA level and growth rate of PSA were indicated as the most significant predictive signs, which could influence on the selection of the patients for conduction of 11C-choline PET/CT in relation to detection of local recurrence after RT and RP.

Correlation of [11C]choline PET-CT with time to treatment and disease-specific survival in men with recurrent prostate cancer after radical prostatectomy.

AIM: Radiotherapy following radical prostatectomy should be considered in men with high risk features who have a life expectancy of more than 10 years. So far no effect on prostate cancer specific survival has been proven by 3 randomized controlled trials (RCTs) on adjuvant radiotherapy. At present the optimal timing of radiotherapy is not defined. Identifying the site of recurrence is difficult at low PSA levels. [11C]choline PET-CT studies in biochemical recurrent prostate cancer after prostatectomy show a higher frequency of (false) negative cases compared to restaging after EBRT. It is uncertain if this reflects low volume of disease and/or low grade as biopsies fail to prove recurrent cancer in 50% of cases. We followed the clinical course of men with recurrent prostate cancer after radical prostatectomy and investigated treatment and survival. PET-CT data were correlated with clinical data, PSA kinetics and disease specific and overall survival. We also studied relative survival comparing an age matched group from the Central Dutch Statistical Office (CBS). METHODS: Sixty-four patients underwent [11C]choline PET-CT on PSA relapse. All patients were initially treated with radical prostatectomy and reached PSA nadir of <0.1 ng/mL. Recurrent disease was defined as PSA increase <0.2 ng/mL after nadir. Patients were either treated with watchful waiting, salvage radiotherapy and/or androgen deprivation therapy based on individual assessments by the treating urologists. Statistic: χ2, log-rank and Mann-Whitney-U tests were used to compare the [11C] choline PET/CT groups. RESULTS: The 64 patients had median PSA of 1.4 ng/mL. Median follow-up period of patients was 50 (6-124) months. Ten patients died during the course of follow-up of which 5 due to metastasized disease. No significant differences were seen in age, time to recurrence, total PSA at recurrence and PET-CT results. Patients with abnormal PET had higher PSAVel (median 3.09 ng/mL/yr versus 10.17, P=0.002) and shorter PSADT (med 4.83 months vs. 0.53, P=0.016). Median time to treatment was significantly lower in the PET-CT negative group. Age of patients at death from the whole group did not differ from the age of death in an age matched group. Disease specific survival was significantly higher in the PET-CT negative group (P=0.05). CONCLUSION: [11C]choline PET-CT showed that a negative PET/CT correlated with a higher disease specific survival and a lower treatment rate in men with a biochemical recurrence after radical prostatectomy. Overall survival of the total group was equal to the age matched cohort emphasizing the limited effect of a biochemical recurrent prostate cancer on overall survival. The optimum timing (adjuvant or early salvage) must be answered in running trials before adjuvant RT is used as standard of care.

[11C]choline PET for the intraprostatic tumor characterization and localization in recurrent prostate cancer after EBRT.

AIM: This study focuses on the potential role of [11C]choline positron emission tomography (PET) for the intraprostatic tumor characterization and localization in recurrent prostate cancer after EBRT. METHODS: This retrospective study was conducted in patients who were being followed up after EBRT for histological proven prostate cancer. We selected the patients with a local recurrence by [11C]choline PET/CT fusion. The results of PET were compared with the results of histology and with clinical follow-up. RESULTS: Forty-two patients with a local recurrence suggested by PET were included in this study. According to PET results: of the 42 patients, 15 (36%) had a focal recurrence, 27 (64%) showed a diffuse recurrence. The overall concordance of PET with histology concerning detection of recurrence was 76% (32 patients had positive PET results and positive biopsies). We confirmed the local recurrence as visualized by PET in 37/42 (88%) patients using a composite reference with histology and clinical follow up after local salvage treatment. The concordance of the intraprostatic distribution of the tumor with PET with histology from transrectal prostate biopsies (median biopsies 7, range 4-12) was 47% (7/15) in unilateral cases and 41% (11/27) in bilateral cases. No significant differences were seen between the 2 groups in serum PSA at time of PET (P=0.509) and SUV (P=0.739) using Student's t-test. CONCLUSION: Intraprostatic characterization of recurrent prostate cancer after EBRT with 11C-choline PET is feasible at present but shows a moderate concordance with routine transrectal prostate biopsies. The accuracy is too low for the routine use of this modality in the present scenario.