Background.Renal cancer is one of the most immunosensitive oncologic diseases. A prominent breakthrough in this field was gained with the development of medications directed to the suppression of PD-1/PD-L immune check-point signaling pathway that in normal physiologic conditions controls autoimmune reactions. Tumor PD-1 and/or PD-L1 expression is investigated both as a predictor of corresponding immunotherapy efficiency, and as molecular markers of overall prognosis and patients’ survival. This goal could be also attained by the measure­ment of soluble forms of these proteins (sPD-1 иsPD-L1) in blood serum.

Objective of the study— comparative evaluation ofsPD-1 and sPD-L1 content in blood serum of practically healthy persons and patients with renal cancer and benign kidney tumors; analysis of the associations between these markers and clinical and pathologic characteristics of renal cancer.

Materials and methods. 106 renal cancer (64 male and 42 female; age 33—81 years) and 11 patients with benign kidney tumors (3 male and 8 female; age 29—84 years) were included in the study. Control group comprised 19 men and 18 women of matching age. 57patients had stage I, 12 — II, 15 — III and 22 — stage IVrenal cancer. Serum sPD-L1 and sPD-1 concentrations were measured using standard enzyme immunoassay kits (Affimetrix, eBioscience, USA).

Results. sPD-L1 levels in blood serum of patients with primary renal cancer and benign tumors were significantly higher than in control (p <0.0001 and p <0.05 respectively). sPD-L1 level significantly increased with disease stage (p <0.001), with T index increase from 1 to 3 declining at T4, was significantly higher in patients with lymph node metastases (both N1, and N2) than in those without such lesions (N0); it was also increased in М+ patients, and in patients with grade III—IVin comparison to grade I—II tumors. sPD-1 levels did not differ sig­nificantly between study groups, did not depend on disease stage, presence of lymph node or distant metastases, but were decreased in patients with Т4 as compared to those with less advanced primary tumor, and were significantly lower in patients with clear-cell than in those with chromophobic or papillary histologic variants.

Conclusion. Serum sPD-L1 in renal cancer patients correlates with disease progression and tumor grade, and can be regarded as promising marker for monitoring of anti-PD1/PD-L1 treatment efficiency. Potential clinical implications of sPD-1 require further investigations and analysis.

Background. Clear-cell renal-cell carcinoma (CCRCC) is the most common histological type of cancer of this localization. Changes in 16 genes were identified as significant in carcinogenesis of CCRCC. After VHL suppressor gene, PBRM1 gene is the second by frequency of genetic abnormalities in CCRCC and it is mutated in 40—50 % cases of CCRCC.

The study objectiveis to analyze the effect of abnormalities in PBRM1 protein expression on survival of patients with CCRCC.

Materials and methods. The study included 137patients with newly diagnosed and histologically confirmed CCRCC. For all study participant, detailed medical history and questionnaire data were acquired. Prior to treatment, blood samples and tumor tissue removed during surgery were obtainedfrom all patients. All patients are annually followed up for current information on their life status, disease dynamics, treatment. Minimalfollow-up time is 22 months, maximal is 128 months, mean is 61.8 months, median is 48 months. Immunohistochemical (IHC) testing of PBRM1 expression was performed using standard technique with polyclonal rabbit antibodies PB1[N1N2] N-term (GeneTex 100781) with 1:50 dilution, DAB staining. Normally, protein product of the wild type PBRM1 gene is functioning and can be detected in the nucleus. Absence of nuclear expression of PBRM1 points to genetic or epigenetic abnormalities.

Results.Renal cancer-specific survival is significantly lower in patients without expression of the PRBM1 protein in tumor cells. The longest 5- (84 %) and 10-year (84 %) survival was observed in patients with diffuse nuclear expression of the PBRM1 protein. Difference in survival of these patients compared to patients without PRBM1 protein expression is statistically significant (p = 0.004). We have performed an analysis of the association between survival of patients with CCRCC andfocal nuclear PBRM1 expression. In these patients, survival is lower than in patients with diffuse expression but higher than in patients without nuclear expression of PBRM1 (p = 0.02). Cytoplasmic expression of PBRM1 doesn’t affect survival.

Conclusion.The obtained results point to prognostic value of PBRM1 gene activity which is abnormal in almost half of all CCRCC cases. IHC testing is an appropriate, reliable and affordable method for determination of PBRM1 protein expression and therefore can be used in practice. Favorable course and prognosis in patients with stage I—II CCRCC and preserved nuclear expression of the PBRM1 protein should be noted: 5-year survival for these patients is 100 %. This observation is crucial for making decisions on treatment of these patients.

Background.Treatment of level II-III inferior vena cava (IVC) tumor thrombus for left renal cell carcinoma is among the most challenging open urologic oncologic surgeries with 38 % complications and 4—10 % mortality rate. There are increasing numbers of centers using a right side laparoscopic radical nephrectomy with thrombectomy at last years but only few reports about laparoscopic management of IVC thrombus from left kidney.

The study objectiveis to demonstrate reproducibility and relative safety of laparoscopic radical nephrectomy with thrombectomy of IVC tumor thrombus originating from the left kidney.

Materials and methods. We describe the method and present the initial series of full laparoscopic level II-III IVC thrombectomy in three patients with tumor in left kidney. One patient had been diagnosed distant metastases before operation, the another — pancreas involvement in the tumor process. The follow up time consist 4—26 months after surgery.

Results. All procedures completed without conversion to open surgery. Tumor sizes were 5—16 cm, length of thrombus in IVC — 2.4—7.0 cm. Volume of blood loss ranged from 300 to 2500 ml. One patient received blood transfusion after surgery. One patient have died because of distant metastases 5 months after surgery. Two others were alive at 4 and 26 months follow-up without signs of progression.

Conclusion.Laparoscopic IVC tumor thrombectomy for level II-III thrombi in cases of left kidney cancer is feasible, safe. This kind of pro­cedure doesn’t lead to serious perioperative complications and can gain a quicker recovery after surgery. It needs more operations and longer follow-up for evaluation oncological efficiency.

The study objectiveis to perform comparative analysis of short-term results of retroperitoneoscopic and laparoscopic radical nephrectomy for large kidney tumors.

Materials and methods. The study is based on the results of examination and treatment of 108 patients with stage Т1—3аrenal cell carcinoma.

Results. For retroperitoneoscopic radical nephrectomy, significant decrease in operative time, ligation and transection of the renal hilum, lower carbon dioxide expenditure, less intense pain sensations on day 1 after the surgery, lower analgesics expenditure, and hospitalization time.

Conclusion. The results show the advantages of retroperitoneoscopic radical nephrectomy compared to laparoscopic nephrectomy.

Background.There is a global increase in incidence and mortality from kidney cancer. Kidney cancer is one of the most common oncological urology pathologies.

Objective:to analyze the mortality data from kidney cancer in the Primorsky Krai population.

Materials and methods. To study the epidemiology of kidney cancer, we used the database of incidence and mortality from kidney cancer of the Primorsky Krai population, formed in the laboratory of epidemiology of the Cancer Research Institute, Tomsk National Research Medical Center, based on data from the cancer register of Primorsky Regional Clinical Oncologic Dispensary and data of the Federal state statistics service. Calculations and analysis of indicators were carried out according to standard methods used in oncoepidemiological studies.

Results.The kidney cancer mortality in males andfemales residing in Primorsky Krai was analyzed for the period 2001 to 2015. The highest kidney cancer mortality rate was observed in patients aged 70—74 years. The average age of patients died from kidney cancer was the sixth decade of their life. The life expectancy for men was shorter by 4.8 years than that for women (p <0.05). The kidney cancer mortality is expected to increase by 7.5 % in men and decrease by 6.8 % in women in 2020, being 7.2 ± 0.7 °/₀₀₀₀ (r² = 0.4) and 2.7 ± 1.4 °/₀₀₀₀ (r² = 0.02), respectively. No statistically significant differences in the rise of kidney cancer mortality rates compared to the rise in the kidney cancer incidence rates were found (p >0.05), therefore, kidney cancer mortality stabilization was observed.

Conclusion.Against the background rising the incidence, the mortality of patients with kidney cancer in population of the Primorsky Krai tends to decline.

Background.New potential biomarker for patients with metastatic hormone-naive prostate cancer (PCa) might be detection of programmed death ligand 1 (PD-L1) expression in tumor which is associated with worsened results of treatment and decreased survival in patients with pancreatic cancer, lung cancer and other malignant tumors.

Objective: to evaluate the prognostic value of positive tumor PD-L1 status on time to castration resistance (CRPCa) in patients with meta­static PCa receiving hormonal androgen deprivation therapy in first-line systemic treatment.

Materials and methods.A total of 35patients with metastatic hormone-naive PCa receiving androgen deprivation therapy with luteinizing hormone-releasing hormone analogue and follow-up at N.N. Blokhin National Medical Research Center of Oncology were recruited in our prospective study. Tumor features of all patients were evaluated for PD-L1 expression on tumor cells by immunohistochemical studies of paraffin block sections obtained under the visual control of the pathologist using a set of monoclonal anti-PD-L1 antibody (28-8) (ab 205921) and Ventana BenchMark GXSlide staining system. Tumor tissue was obtained before starting androgen deprivation therapy. The expression level of PD-L1 >1 % in tumor cells was taken for the positive tumor PD-L1(+) status.

Results. Median follow-up was 32.8 months. Positive tumor PD-L1(+) status was identified in 10 (28.6 %) cases. Median time to CRPCa was significantly lower in patients with PD-L1(+) status, than in negative PD-L1(—) status (21.44 vs. 49.12, p = 0.006 log rank test). Multi­variate Cox regression analysis confirmed independence prognostic value of PD-L1(+) associated with decreased time to CRPCa (hazard ration 5.95, 95 % confidence interval 1.97—17.99; p = 0.002), including in subgroup of patients with low-volume metastatic disease (hazard ration 7.33, 95 % confidence interval 1.81—29.60; p = 0.005).

Discussion. Interaction of PD-1 receptors and its ligands PD-L1/PD-L2 is the key mechanism causing tumor immune escape and progression of the cancer. There are discussed certain ways of inducing PD-L1 expression and its prognostic value on aggressive nonmetastatic PCa. High frequency of positive PD-L1 status was revealed in rare histological subtypes of PCa associated with unfavorable prognosis and visceral metastasis.

Conclusion.The results of our study demonstrated the positive tumor PD-L1 status as an independent unfavorable prognostic factorfor patients with metastatic hormone-naive PCa associated with decreased time to castration resistance, including in patients with low volume metastatic disease.

Background. The indicator of detected cases of prostate cancer (PCa) in 2015 was 38,812. The standardized incidence rate was 40.23per 100,000population. Increase in the incidence of PCa from 2005 to 2015 — 135.5 %. The average annual growth rate is 7.76 %. The histological verification of PCa is of great importance in the diagnosis and subsequent choice of treatment tactics. Currently, the most common method of transrectal “blind” prostate biopsy is to control the control, which does not have sufficient sensitivity and specificity for detecting PCa, and the morphological result contains limited information about the aggressiveness and stage of cancer. In connection with the development of modern methods of magnetic resonance diagnostics, such as multiparametric magnetic resonance imaging, which is currently the most sensitive and specific imaging method for the diagnosis of PCa, methods of targeted prostate biopsy are increasingly used in clinical practice. Scientific work supports the rapidly growing use of multiparametric magnetic resonance imaging (MRI) as the most sensitive and specific imaging tool for detection, lesion characterisation and staging of PCa.

Objectiveis to the safety and frequency of complications of transperineal, transrectal, MRI/TRUS (magnetic resonance imaging/transrectal ultrasound) fusion targeted-biopsy.

Materials and methods.The fusion of magnetic resonance imaging data with transrectal ultrasound enables the targeted biopsy of suspicious areas. 142 consecutively selected patients were examined, mean age of 62.0 + 6.5 years. According to aim we assigned patients to 3 groups: 1^st group (n = 49) underwent repeated transrectal biopsy of the prostate; in patients of 2^nd group (n = 39) perineal biopsy of the prostate; in 3^rd group there were patients (n = 54) a targeted fusion biopsy with magnetic resonance imaging and transrectal ultrasound-navigation. Results. PCa was diagnosed in 26.5, 46.2 and 61.1 % respectively. The most frequent complication of biopsy of the prostate gland was hematuria. This symptom was found in 33.3 % patients of the 1^st group, 42.5 % in the 2^nd group and 42.2 % in the 3^rd group. The prolongation of hospitalization due to hematuria was required by 5patients (11.9 %) from 1^st group, 8 (17.0 %) from 2^nd and 5 (7.8 %) from group 3. Hospitalization and additional treatment was required in 8 (16.3 %) patients in 1^st group and 1 (2.5 %) in 2^nd group. Infectious-inflammatory complications are often diagnosed and require additional treatment. In 1^st group patients, this type of complication was observed in 16.3 %, 2^nd and 3^rd groups 5.1 % and 1.9 %, respectively. In 4.7 % of the patients in the 1^st group, sepsis was diagnosed, complications were not recorded in patients of groups 2^nd and 3^rd of the data group. When assessing the complications, there was a slight predominance of the complication rate of the standard transrectal biopsy procedure, but this difference was statistically insignificant (p >0.05).

Conclusion. We compared the security of standard biopsy and perineal biopsy to diagnose PCa against a novel approach using software to overlay the images from magnetic resonance imaging and ultrasound to guide biopsies towards the suspicious areas of the prostate. We found consistentfindings showing the superiority of this novel targeted approach, although further high-quality evidence is needed to change current practice. No significant statistical differences were found in the complications rates between.

Background.Patients suffering from prostate cancer (PCa) with a high risk of progression need the most active treatment tactics. Escalation of radiation dose, larger daily fractions radiation therapy (including high-dose-rate interstitial brachytherapy (HDR-BT)) is a promising approach to the treatment of PCa.

Objective of the study. Comparative assessment of the long-term treatment results of patients with PCa with a poor prognosis after external beam radiotherapy (EBRT) and combined radiation therapy, depending on risk factors.

Materials and methods. 207patients who received a course EBRT and HDR-BT with EBRT (combined RT) on a radical program for the first detected PCa at the N.N. Alexandrov National Cancer Center of Belarus in 2013—2015 inclusive. All patients were belonged to the group of

high and very high risk of progression according to the criteria of the NCCN (National Comprehensive Cancer Network), all were treated with neoadjuvated hormone therapy (medical or surgical castration).

The patients were stratified into two groups: HDR-BT with EBRT and EBRT. When conducting combined RT, HDR-brachytherapy was performed in single fraction with a dose of 11.5 Gy, for EBRT it was used as a conventional fractionation (single dose of 2 Gy, total — 44 Gy) and hypofractionation (single dose of 3 Gy, total — 36 Gy). Patient that were not who not included in the combined RT protocol were treated with EBRT under a radical program in a total dose of 78—80 Gy.

Results. It was established that in the group of patients after EBRT the median survival was not achieved, the 5-year adjusted survival (AS) was 85.2 + 5.6 %. In the combined RT group, the median survival was also not reached, the 5-year-old AS was 92.2 + 5.9 %. It was found that for the patients with a Gleason score of 7 or more, a significant difference in the AS index was obtained in favor of the HDR-BT with EBRT: the 5-year AS of patients of this subgroup who were exposed to combined RT was 84.6 + 9.8 %, while after EBRT, the 5-year-old AS was 71.0 + 11.2 %. In the subgroup of patients with Gleason sum 7—10, combined RT was associated with statistically significantly better long-term results in compared with EBRT.

Conclusion.The application of the method of combined RTfor patients suffering from PCa with a high risk is characterized with satisfactory long-term treatment results.

Prostate cancer (PC) is one of the most pressing problems of modern oncology due to high worldwide morbidity for this pathology. Annually, more than 1,100,000 new cases of PC are diagnosed worldwide. The main treatment method for patients with locally advanced and/or metastatic PC is hormone therapy. Androgen deprivation allows to achieve disease stabilization in more than 90 % of patients, but mean time to progression after hormone therapy in patients with metastatic PC is about 2 years. Patients with cancer progression and preserved castration level of testosterone transition to the stage of so-called castration-resistant prostate cancer (CRPC). Advanced CRPC not only has poor prognosis, it also significantly decreases quality of life of the patients. CRPC patient cohort is extremely heterogenous and included patients both with factors of favorable prognosis and fulminant course of the disease. Unfavorable prognostic factors for patients with metastatic CRCP are short response time for initial hormone therapy (<12 months), presence of pain syndrome as well as presence of visceral metastases. Taxane chemotherapy remains one of the standard treatment methods in patients with metastatic CRPC and unfavorable prognostic factors.

The article presents a review of studies dedicated to the effectiveness of various doses and regimens of 2^nd line chemotherapy using cabazi-taxel in patients with metastatic CRPC as well as analysis of clinical cases of using this drug in real-life clinical practice.

During cancer progression Notch signaling pathway and its components could demonstrate oncogenic and tumor-suppressive properties depending on tissue type and cellular microenvironment. However, until recently, very little was known about Notch role in bladder cancer (BC). According to recent studies it was revealed that loss of copy number and decreased expression of NOTCH1 is the hallmark of BC cell lines; and NOTCH1 activation in vitro reduces cell proliferation, suggesting that NOTCH1 acts as a tumor suppressor in BC. Furthermore, BC could be promoted by bladder-specific inactivation of a component of y-secretase complex, which is directly involved in Notch signaling, in vivo. By contrast, further studies have demonstrated that NOTCH2 acts as an oncogene which could promote cell proliferation and metastasis through induction of epithelial-to-mesenchymal transition and maintaining stemness. Studies indicating that NOTCH1 and NOTCH2 have opposite effects on BC progression could give rise to novel therapeutic approaches aimed at impact on Notch activity.

Prostate cancer is the largest problem among the male population of the planet, despite the slow development of the disease, thousands of men die from this disease every year. Taking into account the following facts, we can say about the importance and relevance of this problem. This review highlights the results of different treatment strategies for high and very high risk prostate cancer.

Until now selection of the 1st line therapy for advanced clear-cell renal cell carcinoma was determined by patients distribution into favorable/ intermediate or poor prognosis groups. In the favorable/ intermediate prognostic groups agents of choice included antiangiogenic substances such as bevacizumab (in combination with interferon-alpha), sunitinib, andpazopanib, which had demonstrated only progression-free survival benefit comparing with interferon-alpha in registration studies; in the poor prognosis group the only treatment option was mammalian target of rapamycin inhibitor temsirolimus which had improved overall survival comparing with interferon-alpha. However about 75 % of advanced renal cell carcinoma patients have intermediate or poor prognosis. Only 2 randomized trials investigated systemic therapy in this cohort of patients, CABOSUN and CheckMate 214. The results of the randomized phase III study CheckMate 214 have demonstrated a significant advantage of overall survival and objective response rate in previously untreated patients of intermediate/poor prognostic groups who were randomizedfor combined immunotherapy with nivolumab and ipilimumab comparing with sunitinib independently of PD-L1 expression level. Owing to the achieved data combined immunotherapy became a new standard of the first-line therapy in advanced renal-cell carcinoma patients with intermediate and poor prognosis.

The study objective is to evaluate the results of adjuvant intravesical chemotherapy (IVCT) using an original penetrant titanium glycerosolvate aquacomplex (TGA) compared to the standard technique of chemotherapy drug instillation in patients with high risk non-muscle-invasive bladder cancer.

Materials and methods. The prospective study included 110 patients with non-muscle invasive bladder cancer. The treatment group (n = 55) included patients with high risk non-muscle-invasive bladder cancer who received a 6 week course of adjuvant IVCT with TGA; the control group (n = 55) included patients with high and intermediate risk non-muscle-invasive cancer who received a 6 week course of IVCT using the standard instillation technique: with chemotherapy drugs diluted in 0.9 % NaCl saline. Comparison of the effectiveness of the two techniques of adjuvant IVCT was performed using recurrence-free survival, progression and side effect rates. Significance was stated at p <0.05.

Results. Median follow-up duration in the treatment group was 58 months, in the control group — 50 months (p >0.05). Disease progression was observed in 1 (1.8 %) patient in the treatment group and in 3 (5.4 %) patients in the control group (p >0.05). Median recurrence-free survival in the treatment group wasn’t reached, in the control group it was 52 months. Five-year recurrence free survival in the treatment group was 17 % higher than in the control group (64.9 % vs 47.9 %; p = 0.068). Despite the absence of significant differences between recurrence-free survival in the compared groups, a tendency toward its increase is observed in the treatment group after 12 months (p = 0.079). Side effects observed for the two instillation methods were toxicity grade I—II.

Conclusion. Use of compositions of chemotherapy drugs with TGA as adjuvant IVCT allowed to improve the results of treatment of high risk non-muscle-invasive bladder cancer compared to the standard technique of instillation of chemotherapy drugs.

The objective is to study the possibility of using the obturator nerve block under the control of nerve stimulator to prevent the thigh adductor muscles spasm during transurethral resection of bladder tumor.

Materials and methods. The prospective randomized study included data obtained during the surgical treatment of 50patients with lateral wall bladder tumor, which was subjected transurethral resection of the bladder. In the GA group (n = 25) was performed general anesthesia with use muscle relaxants, in the NS group (n = 25) spinal anesthesia was performed in combination with obturator nerve block by 10 ml of a 2 % solution of lidocaine under the control of nerve stimulation.

Results. The thigh adductor muscles spasm was observed in 5 cases (25 %) in the GA group and in 3 cases (12 %) in the NS group (p = 0.702), this was the cause of bladder perforation in 1 (4 %) patient in the NS group. The incidence of arterial hypotension in the NS group was lower than in the GA group (0 % versus 32 %; p = 0.004), as well as the incidence of sinus bradycardia (12 % versus 48 %; p = 0.012). The time of being in operating room in the NS group was 45 minutes (40; 53) versus 60 minutes (50; 85) in the GA group (p = 0.006).

Conclusion. The spinal anesthesia in combination with obturator nerve block under the control of nerve stimulation, as well as the general anesthesia with use muscle relaxants did not guarantee the absence of adductor muscles spasm during transurethral resection of the lateral wall bladder. The obturator nerve block under the control of nerve stimulation only can not be recommended to prevent perforation of the bladder wall in these interventions.

Small cell cancer of the prostate is extremely rare. No sound on the research recommendations for the treatment of patients with small cell cancer of the prostate. The article gives its own observation of the patient’s small cell cancer of the prostate. A discussion of possible methods to treat such patients using own results and literature data.

Annual Genitourinary cancers symposium of the American society of clinical oncology (ASCO GU 2019) took place between 14th and 16th February in San Francisco (CA, USA) united more than 4,500professionals from 65 countries. In this article, a review of the most significant reports from the ASCO GU 2019 is presented.