Search

Objective: to study the clinical and demographic profile of patients with non-metatstatic castration-resistant prostate cancer (nmCRPC) and clinical approaches to the treatment of nmCRPC in the context of daily medical practice before and after progression M1 stage.Materials and methods. The multicenter non-interventional epidemiological study is planned to include 200 patients with a documented diagnosis of nmCRPC from 2019 to 2020. The interim report has included data on 108 patients from 13 centers located in different regions of the Russian Federation. The median age of the patients was 73 (55—90) years.Results and conclusion. When the diagnosis of nmCRPC was made, the median prostate specific antigen was 8.23 (0.17—116.9) ng/ml, and the prostate specific antigen doubling time was 6 (1—50) months. When diagnosed nmCRPC, 86 patients (79.6 %) underwent a change of therapy, of which 42 % were prescribed modern regimens containing the new generation non-steroid antiandrogens (apalutamide, enzalutamide).

The use of immunotherapeutic drugs as monotherapy and in various combinations for metastatic renal cell carcinoma has revolutionized the treatment of this disease. Thanks to the breakthrough studies carried out, the standard in the first line of therapy for metastatic renal cell carcinoma is now a combination of checkpoint inhibitors, as well as an immuno-oncological agent with a tyrosine kinase inhibitor.This article presents updated data from the CheckMate 214 study with a minimum follow-up of 42 months. A review of studies on the efficacy of nivolumab in patients with renal cell carcinoma in the first line of therapy with the possibility of adding ipilimumab in case of progression of the disease on the background of monotherapy is carried out, as well as data on the use of a combination of nivolumab and ipilimumab in the second line of treatment.Monotherapy with nivolumab has a certain effectiveness in a specific category of patients, for example, with potential intolerance to ipilim-umab or first-line tyrosine kinase inhibitors, as well as in patients with a favorable prognosis.The combination of drugs nivolumab + ipilimumab is a highly effective treatment option in the first line of therapy with the potential for a sustained response in patients with RCC with an poor and intermediate risk, and in the second and subsequent lines requires further study.

Urethral diverticula are sac-like dilatations of the urethra that communicate with its lumen. They may be congenital or acquired. In males, urethral diverticula are rare and classified as congenital (true) and acquired, which are associated with trauma, abscess, strictures, surgical procedures, in particular in patients with hypospadias. A clinical observation of urethral diverticulum with two stones in a man after complex treatment of prostate cancer with metastasis to the left cavernous body of the penis is presented in the article. At the first stage, the patient underwent endoscopic lithotripsy with a biopsy of the diverticulum wall and laser ablation of the stricture of urethrovesical anastomosis. At the second stage the excision of the diverticulum with urethroplasty was performed. The team of authors considers this clinical observation to be unusual. Previously, postoperative urethral diverticula with two stones in patients after complex treatment of prostate cancer with metastasis to the left cavernous body of the penis was not described in the scientific literature.

Previously presented Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) system was developed on the basis of consensus that was achieved by the results of published studies containing expert and analytical conclusions. Numerous studies on PI-RADS v2, not only confirmed the importance of a unified system in the diagnosis of prostate cancer, but also revealed a number of limitations. In order to eliminate flaws of PI-RADS v2, a number of potential solutions were proposed. The PI-RADS Steering Committee recommended changes in PI-RADS v2, with maintaining the structure of sequence scoring and using these scores to obtain the final category. The updated version was published as PI-RADS v2.1 at the beginning of 2019. It is expected that the use of PI-RADS v2.1 will optimize and simplify the evaluation magnetic resonance imaging of prostate and reduce the number of interpretation errors. At the same time, it is necessary to continue further studies on the assessment of the clinical significance of this system when choosing a treatment strategy and monitoring patients with a high potentialfor the development

Background. Renal cell carcinoma is a heterogeneous group of tumors characterized by high vascularization and immunogenicity. Immunotherapy has made a breakthrough in the treatment of this pathology, however, the lack of development of criteria for its use does not allow to achieve even greater success. It is known that the tumor stroma plays an important role in the success of immunotherapy. Among the various histological types of kidney tumors, the stroma of the clear cell renal cell carcinoma has been studied in sufficient detail. However, the remaining histological types are practically not studied. Objective: description of the immunosuppressive phenotype of the stroma of kidney tumors of various histological types. Materials and methods . The study included tumor samples obtainedfrom 44patients with renal cell carcinoma of various histological types (16 samples of chromophobe cancer, 15 samples of clear cell and 13 samples of papillary renal cell carcinoma). The method of immunohis-tochemistry evaluated the expression of tumor stromal markers, namely CD68, CD206, PU.1, CD3, IDO1 and PD-L1 in the studied samples. Results . Analysis of the total number of macrophages associated with the tumor showed that the smallest number is observed in samples of chromophobe renal cancer, while in the samples of clear cell cancer their number is greatest. A similar situation is observed for T-cells: the largest number of CD3+ cells is observed in clear cell tumors. In chromophobe and papillary tumors, their number is reduced. Papillary tumors are also characterized by an almost complete absence of expression of PD-L1 and IDO1 compared to other histological types of kidney tumors. We also showed that for PU.1 there is a strong positive correlation between its quantity and localization, as in CD68. Thus, PU.1 can be used as a general marker for describing stromal macrophages in kidney tumors. Conclusion. The study showed that kidney tumors of various histological types strongly and significantly differ in the composition of their microenvironment. These data, of course, must be considered when choosing immune therapy in the treatment of this pathology.

Background. Atezolizumab can induce sustained responses in metastatic urothelial carcinoma. We report the results of IMvigor130, a phase III trial that compared atezolizumab with or without platinum-based chemotherapy versus placebo plus platinum-based chemotherapy in first-line metastatic urothelial carcinoma. Materials and methods. In this multicentre, phase III, randomised trial, untreated patients aged 18 years or older with locally advanced or metastatic urothelial carcinoma, from 221 sites in 35 countries, were randomly assigned to receive atezolizumab plus platinum-based chemotherapy (group A), atezolizumab monotherapy (group B), or placebo plus platinum-based chemotherapy (group C). Patients received 21-day cycles of gemcitabine (1000 mg/ml body surface area, administered intravenously on days 1 and 8 of each cycle), plus either carbo-platin (area under the curve of 4.5 mg/mL per min administered intravenously) or cisplatin (70 mg/ml body surface area administered intravenously) on day 1 of each cycle with either atezolizumab (1200 mg administered intravenously on day 1 of each cycle) or placebo. Group B patients received 1200 mg atezolizumab, administered intravenously on day 1 of each 21-day cycle. The co-primary efficacy endpoints for the intention-to-treat population were investigator-assessed Response Evaluation Criteria in Solid Tumours 1.1 progression-free survival (PFS) and overall survival (OS) (group A vs group C) and OS (group B vs group C), which was to be formally tested only if OS was positive for group A versus group C. The trial is registered with ClinicalTrials.gov, NCT02807636. Results. Between July 15, 2016, and July 20, 2018, were enrolled 1213patients. 451 (37 %) were randomly assigned to group A, 362 (30 %) to group B, and 400 (33 %) to group C. Median follow-up for survival was 11.8 months (interquartile range 6.1—17.2 months) for all patients. At the time of final PFS analysis and interim OS analysis (May 31, 2019), median PFS in the intention-to-treat population was 8.2 months (95 % confidence interval (CI) 6.5—8.3) in group A and 6.3 months (95 % CI 6.2—7.0) in group C (stratified hazard ratio 0.82; 95 % CI 0.70—0.96; one-sided p = 0.007). Median OS was 16.0 months (95 % CI 13.9—18.9) in group A and 13.4 months (95 % CI 12,0—15.2) in group C (0.83; 95 % CI 0.69—1.00; one-sided p =0.027). Median OS was 15.7 months (95 % CI 13.1—17.8) for group B and 13.1 months (95 % CI 11.7—15.1) for group C (1.02; 95 % CI 0.83—1.24). Adverse events that led to withdrawal of any agent occurred in 156 (34 %) patients in group A, 22 (6 %) patients in group B, and 132 (34 %) patients in group C. 50 (11 %) patients in group A, 21 (6 %) patients in group B, and 27 (7 %) patients in group C had adverse events that led to discontinuation of atezolizumab or placebo. Conclusion . Addition of atezolizumab to platinum-based chemotherapy as first-line treatment prolonged PFS in patients with metastatic urothelial carcinoma. The safety profile of the combination was consistent with that observed with the individual agents. These results support the use of atezolizumab plus platinumbased chemotherapy as a potentialfirst-line treatment option for metastatic urothelial carcinoma.

Background. Currently there exists a wide range of advanced renal cell carcinoma (RCC) treatment schemes, among them cabozantinib, registered in Russia in 2019, was approved as a second-line therapy in both foreign and domestic guidelines. Objective: to conduct a comparative clinical and economic analysis of cabozantinib and alternative drugs in adult patients with advanced RCC after previous systemic therapy. Materials and methods. A literature review was conducted on clinical efficacy and safety of various second-line therapy drugs for advanced RCC in the available databases. The foreign partitioned survival model, reflecting the development of widespread RCC when using 4 different second-line therapy drugs (cabosantinib, nivolumab, axitinib and everolimus), was adapted considering 3 consecutive mutually exclusive conditions (before progression, after progression, death). Pharmacoeconomic analysis included “cost-effectiveness” and “cost-utility” analysis. We estimated direct medical costs for second- and third-line therapy and maintenance therapy (outpatient monitoring and palliative care). To estimate drug costs we used prices from the State Register of maximum selling prices, for cabozanthinib — price presented by the manufacturer. Costs of maintenance therapy were estimated based on the normal standardfor financial costs in accordance with the Program of state guarantees for 2020. Results. Efficacy analysis based on the partitioned survival model showed the highest rates of life-years gained (3.18 life-years-gained (LYG)) and quality adjusted life-years (1.87quality adjusted life-years (QALY)) for cabozanthinib compared with nivolumab (2.53 LYG and 1.6 QALY), axitinib and everolimus (2.21 LYG and 1.31 QALY). Total costs for advanced RCC patients when treated with cabozanthinib were 4.3 million rubles, which is 5 % less than when using nivolumab (4.5 million rubles). Total costs for axitinib were 2.1 million rubles, while its effectiveness was lower compared with the cabozanthinib one. Costs of 1 life-year saved for cabozantinib were 1.4 million rubles, which is 25 % less compared to those for nivolumab. Costs of 1 quality-life year saved when using cabozantinib amounted 2.3 million rubles, which is 19 % less than those for nivolumab. Conclusion. The study results showed that using cabozantinib to treat advanced RCC after previous systemic treatment is both clinically and cost-effective for adult patients with advanced RCC in the Russian Federation.

Objective: to study the frequency and dynamics of morbidity and mortality in male population of Omsk region with prostate cancerfor the period from 2005 to 2010. Materials and methods . A retrospective analysis was carried out for the periodfrom 2005 to 2010 of the initial diagnosis of1840patients with prostate cancer and the causes of death of837men in the Omsk region. The contingents of patients with prostate cancer were studied depending on the geographic location, size and composition of the region’s population. The data of the updated base of the population cancer registry and the main reporting forms were used. Results. There was an increase in the absolute number of diagnosed patients with prostate cancer for the first time by an average of 9.9 % annually. The downward trend was in the number of patients with I—II tumor stage lesions. Stable high annual detection of patients was with stage III (more than 50 %). The advanced forms of prostate cancer accounted for up to 24.4 %. The absolute number of men registered had increased by 52.4 %. The annual mortality rate decreased by an average of 5.7 %. During the monitoring period the absolute number of dead patients increased by an average of 6.7 % annually. Conclusion. The development and regional implementation of the Program for the early diagnosis and screening of prostate cancer based on a set of simple and generally accessible methods is advisable.

Materials and methods. From September 19, 2016 to December 27, 2019, 104 patients received cabazitaxel plus prednisone for a maximum of 10 cycles or disease progression, or unacceptable toxicity, or patient request to stop treatment. Adverse events occurring during treatment, including use of granulocytic colony stimulating factors, were collected. Prostate specific antigen response, objective tumor response (RECIST), progression-free survival and overall survival were analyzed. Treatment period was followed by a follow-up period of 82.0 (36.0–117.0) weeks. Results. 104 patients with histologically proven adenocarcinoma were enrolled and treated. All were Caucasian with a median age of 66 (range 46.0–86.0) years and a median BMI-Score of 26.8 (18.7–43.3) kg/m2. Most patients (57/104, 54.8 %) were ECOG 1. At the time of prostate cancer diagnosis, 63/104 (60.6 %) patients had metastatic disease. The median duration of therapy was 14.5 (0.1–39.0) weeks and the median number of cycles cabazitaxel was 5; 30 (28.8 %) patients received 10 cycles of treatment. Granulocytic colony stimulating factors was received by 52 (50.0 %) patients (prophylactic, n = 31; curative, n = 21). Overall, 102/104 (98.08 %) patients reported at least one treatment emergent adverse event (TEAE), 21/104 (20.19 %) grade ³III TEAEs and 12/104 (11.54 %) serious adverse events. Most TEAEs resolved but 9/104 patients discontinued treatment due to TEAE. Most common TEAEs were related to gastrointestinal system disorders (46/104 (44.23 %) patients, mainly nausea n = 40); blood and lymphatic system disorders (44 (42.31 %) patients, mainly leukopenia n = 22, anemia n = 15, neutropenia n = 11) and general disorders/administration site conditions (22 (21.15 %) patients; mainly asthenia n = 21). Main grade ³III adverse events were related to blood and lymphatic system disorders (11 (10.58 %), including one case of febrile neutropenia), general disorders/administration site conditions (6 (5.77 %), mainly asthenia) and cardiac disorders in 2 (1.92 %) patients. A prostate specific antigen decline of at least 50 % was observed in 23 out of 31 patients with evaluable prostate specific antigen measurements. The objective tumor response was observed in 29 (27.9 %) patients, including 7 (6,7 %) with complete response and 22 (21.2 %) with partial response. Treatment was completed as initially planned in 41/104 (39.4 %) patients, and 61/104 (58.7 %) reached the last follow-up visit. At the last follow-up visit, median overall survival was not reached due to a low number of events. Median progression-free survival at the end of treatment visit was 6.29 (5.1–10.45) months and reached 10.13 (5.55–19.27) months at the last follow-up visit. There was no reported death related to treatment of cabazitaxel during the period of treatment and follow-up period. Conclusion. This prospective, multi-center, national observational, non-interventional register conducted in patients with mCRPC in Russian Federation suggests that cabazitaxel is effective with a manageable safety profile.

Radiopharmaceuticals previously used to treat patients with metastatic castrate-resistant prostate cancer and skeletal metastases were positioned as means to suppress pain, reduce analgesics consumption and improve the quality of life. They were usually administered once in case of progressive pain syndrome. Radium chloride [223Ra] is registered to treat patients with castrate-resistant prostate cancer and multiple skeletal metastases, but without visceral metastases. The ALSYMPCA study showed a significantly increased overall survival in the group receiving radium chloride [223Ra] compared with placebo. This became the basis to register the drug, as well as to include the treatment into the clinical guidelines of professional associations in various countries of the world. The secondary endpoints of the ALSYMPCA study were evaluation of the quality of life, the influence of radium chloride [223Ra] on pain severity, the dynamics of tumor and biochemical markers, and the time to the first skeleton associated complication. Thus, the main goal of radium chloride [223Ra] therapy is to prolong patients’ life, and it can be prescribed to those with or without pain syndrome. The data served as the basis for widespread use of radium chloride [223Ra] to treat patients with castrate-resistant prostate cancer and skeletal metastases

Background. We have previously described an algorithm APhiG (Age of patients, Prostate health index and Gleason score), for staging of prostate cancer before treatment. The algorithm was developed by logistic regression on a training dataset and validated on a validation dataset (VD). Objective. Validation of threshold decision rules and a program for APhiG calculation on the VD.Materials and methods. ROC curve analysis on VD (83 cases).Results and conclusion. It was shown that sensitivity, specificity, positive and negative predictive value, diagnostic accuracy threshold decision rules and area under the curve (AUC) for APhiG in the VD (n = 83) not significantly different from those indicators in the training dataset (n = 337), which was the basis for the algorithm APhiG development.

Objective: The morbidity of multiple urological malignances is steadily grown. Incidental prostate cancer in patients with bladder cancer seems to be fairly often. This is one of the reasons of that the question of partial sparing of prostate in patients undergone radical cystoprostatectomy is still discussable. Purpose: The present study is designed to evaluate the incidence of simultaneous prostate and bladder cancer in patients undergoing radical cystoprostatectomy in Moscow Scientific Research Institute of Oncology.Materials and methods: From 1994 to 2005, 113 men (mean age 59,5 years), with no evidence of prostatic malignancy on preoperative clinical and biochemical assessment, underwent cystoprostatectomy for TCC of the bladder in our institute. The bladder was adequately sampled and the entire prostate sectioned at 5-mm intervals and examined histologically, in order to identify unsuspected prostatic cancer (PCa).Results: 10 out of 113 patients (8,8%) were found to have PCa. Four (3,5%) had cr. in situ, five (4,4%) had high grade prostatic intraepithelial neoplasia (PIN). All tumors were clinically significant, except cr. in situ and PIN. Almost all tumors (7,9%) were organ confined (pT2a—T2c), except one (0,9%), which was locale advanced (pT3a). Glaeson score was 2—4 in 5 (26,3%) and 5—7 in 5 (26,3%).Conclusions: Incidental PCa is quite a common finding in cystoprostatectomy specimens of bladder cancer patients. This demands careful and complete excision of the prostate in patients with muscular-invasive bladder cancer.

The results of interactive voting on the problem of therapeutic strategy in different stages of prostatic cancer are summed up. The voting was carried out at the VIth All-Russian Conference "Pressing Problems in Oncourological Diseases". Based on the results of priority studies and metanalyses, the authors discuss a wide spectrum of disputable problems concerning the indications for radical surgery, hormone and symptomatic treatment of the disease.

Castration-resistant prostate cancer (CRPC) has a very negative prognosis. The average life expectancy even using modern treatment methods is 1.5–2 years. When the majority of CRPC patients show signs of resistance to therapy aimed at lowering testosterone levels, distant metastases are often determined in the bones. Bone metastases in CRPC patients often worsen life quality due to pain and risk of bone complications, such as pathological fractures and spinal cord compression. Not all treatment regimens to increase their life expectancy patients are effective. Radiopharmacy using alpha-emitting radium-223 chloride is not only one of the methods of palliative treatment, but also one of the most promising therapies that increase life expectancy of these heavy patients. Results of large randomized trials showed that alpha-therapy with radium-223 chloride leads to a significant increase of the overall life expectancy, and significantly improve the patients’ life quality. The article presents literature review as well as the analysis of the results of large randomized trials, which assess the effectiveness of the therapy in CGRG patients, and a clinical case of its use in real clinical practice.

Improving the laboratory diagnosis of prostate cancer and bladder cancer are still an actual problem in modern urologic oncology. Test systems for DNA or RNA alterations that occurred during carcinogenesis and associated with the malignant tumor and the prognosis of disease have been actively developed in recent years. Here we reviewed the data published mainly in the last 5 years about the molecular genetic kits for diagnosis (Progensa, SelectMDx, ExoDx Prostate Test, Prosta-Test, Confirm MDx) and assessment of prognosis (Prolaris, Decipher, Oncotype DX) in patients with prostate cancer, discussed their sensitivity and specificity. The characteristics of analogous kits and panels for bladder cancer (UroVysion, CertNDx Bladder Cancer Assay, UroSEEK, mutations in the FGFR3 and TERT genes, and the Cxbladder Monitor/Detect/Triage kit's line) were systematized. Particularly we focused on the description of the patient cohorts for whom kits mentioned above have greater diagnostic accuracy, described limitations of these test systems in consequence both a methodological and registration aspects, and their use in combination with other tumor markers. This review is aimed at oncologists, urologists, laboratory geneticists and specialists in related professions.

The last decades are characterized by an active search for highly sensitive and specific urinological and serological tumor-associated markers of renal cell carcinoma. This review analyses the results of studies of traditional serological tumor-associated markers and a potential new tumor-associated marker of renal cell carcinoma: kidney injury molecule-1, or KIM-1. The structure, sources and functions of KIM-1 in normal conditions and in damaged renal tubules, its potential role in carcinogenesis are described. The experience of using KIM-1 for specifying diagnosis of the most common histological types of renal cell carcinoma is analyzed. Data on KIM-1 expression in malignant tumors in other locations and non-oncological kidney disorders are presented. The role of KIM-1 in early diagnosis of nephrotoxic effect of antitumor drugs is described. The accumulated data is promising in regards to using KIM-1 in clinical oncology as a urinological and serological marker of renal cell carcinoma and chemotherapy nephrotoxicity.

Currently, enzalutamide is the standard of pharmaceutical therapy of metastatic and non-metastatic castration-resistant prostate cancer. However, until recently there was no data on effectiveness and safety of enzalutamide in metastatic hormone-sensitive prostate cancer. Results of 2 large randomized clinical trials ARCHES and ENZAMET showed that early prescription of enzalutamide in combination with standard androgen deprivation therapy allows to significantly increase survival of patient with metastatic hormone-sensitive prostate cancer. The review describes data of these trials and advisability of prescribing enzalutamide in combination with androgen deprivation therapy as 1st line therapy of metastatic hormone-sensitive prostate cancer.

A multidisciplinary approach is currently a necessary and standard approach in treatment of cancer patients. The main goals of the multidisciplinary approach include coordinated highly effective interaction of medical specialists to timely identify, prescribe and conduct planned treatment, as well as prevention and correction of adverse events of treatment to achieve most lasting effect of treatment. The article discusses role of multidisciplinary team, including an oncologist, urologist, pathomorphologist, molecular genetics, radiologist, medical oncologist, radiation therapist, neurosurgeon, orthopedic surgeon, endovascular, thoracic and abdominal surgeons for effective treatment of oncourological patients. To solve existing problems, it is necessary to create common standards for the treatment of oncological diseases, develop and improve an oncological care system, improve logistics and improve skills of specialists or train specialists in the required profile.

—A mathematical model is proposed to describe and solve problems of medical diagnostics and forecasting based on a risk criterion. Within the framework of the model, problems with ranked diagnoses are considered, whose solution benefits from taking medical preferences into account. A diagnostic algorithm, which is the implementation of this model, is used to solve the problem of predicting the clinical status of prostate cancer. A comparative analysis of the quality of the prediction for four model options was carried out, informative prognostic indicators were revealed, and the results were interpreted. Taking medical preferences into account increases the accuracy of prediction for patients with more frequent and aggressive tumor process due to loss of accuracy for patients with less frequent and aggressive tumor process.

Background. We have previously described an algorithm APhiGT (Age, Prostate Health index, Gleason score, TNM stage) for staging of prostate cancer (PC) before treatment. The algorithm was developed by logistic regression on an educational selection (ES) of 337 PC cases. The algorithm includes data about the age of patients, the levels of total prostate-specific antigen (PSA), free PSA, [-2]proPSA and the ranked data of the Gleason score (by biopsy results) and T (by TNM).Objective. Validation of APhiGT on the validation selection (VS) of 83 PC cases was carried out in this work.Materials and methods. ROC analysis was performed in ES and VS.Results and сonclusion. It is established that area under the curve (AUC), characterizing the ability to divide clinically significant subgroups of patients (Gleason score

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 (

One of actively developing trends in modern pharmacology is the use of the transcriptome analysis for drug repositioning. We have previously detected two molecular markers of relapses in patients with malignant breast tumors: ELOVL5 and IGFBP6. Poor prognosis is associated with low expression of these markers. Here we analyze the effects of simvastatin and a new potential proteasome inhibitor K7174 inducing expression of IGFBP6 and EVOVL5 on the proliferation of breast cancer cells MDA-MB-231 and DU4475. Compound K7174 potentiates the inhibitory effect of simvastatin on the proliferation of DU4475 cells characterized by low expression of ELOVL5-IGFBP6 pair, but not on the proliferation of MDA-MB-231 cells with high expression of these markers.

Metastatic cascade is associated with the process of epithelial-mesenchymal transition accompanied by changes in cell proliferation, migration, adhesion, and invasiveness mediated by the insulin-like growth factor (IGF) signal pathway. IGFBP6 protein binds IGF and prevents its interaction with receptors. IGFBP6 gene knockdown through RNA-interference inhibits cell migration and increased the rate of proliferation of breast cancer MDA-MB-231 cells. IGFBP6 knockdown cells are characterized by increased expression of MIR100 and MIRLET7A2 genes encoding hsa-miR-100-3p, hsa-miR-100-5p, hsa-let-7a-5p, and hsa-let-7a-2-3p miRNA. The target genes of these microRNAs are IGF2, IGF1R, INSR, and CCND1 associated with IGF signaling pathway and proliferative and migratory activity during the metastatic cascade. A significant decrease in the expression of INSR and CCND1 genes was demonstrated by PCR and microarray analysis.

Bladder cancer (BC) is represented by non-muscle-invasive forms at the stage Ta, T1, CIS (NMBC) in 75 % of cases. The gold standard of treatment of NMBC patients is transurethral resection, but its implementation does not always allow the patient to be relieved of the recurrence of the disease. In this regard, patients with a low risk of progression after transurethral resection are administered by intravesical chemotherapy, with high risk (T1G2/3) – using instillation with BCG (Bacillus Calmette–Guerin) vaccine. Searching of NMBC markers for laboratory diagnostics, which would help to determine sensitivity or resistance to the planned type of adjuvant therapy remains an actual problem. The data published mainly in the last 5–7 years about genetic predictors of the response to adjuvant chemotherapy and, to a greater extent, immunotherapy with BCG vaccine, are reviewed in this work. Allele combinations in the genes involved in immune response, xenobiotic biotransformation and other loci that are associated with the response to the adjuvant NMBC therapy in meta-analyzes are systematized. Also, expression profiles of mRNA, microRNA and proteins, as well as panels of methylated loci associated with the effectiveness of chemotherapy and immunotherapy of NMBC are considered. It was demonstrated that the somatic mutations sequencing in the primary tumor and the total mutational load using high-throughput sequencing technologies (NGS) identified a number of potential prognostic markers. Perhaps, the mutational load will be more widely used as a highly informative predictor of immunotherapeutic effect in BC: BCG therapy of NMBC and BC targeted therapy using the inhibitors of immune control points, after the standardization of the analysis. This review is intended to oncologists, geneticists, molecular biologists, urologists, pathologists and other specialists working in the field of molecular genetics in oncological urology.

Objective : to develop and substantiate the method of stabilization of urethrovesical anastomosis with retropubic prostatectomy to improve the results of early recovery of urinary retention. Materials and methods . 58 patients who had undergone radical prostatectomy were enrolled into the prospective study. The patient population was divided into two groups by the blinded randomization. The first control group consists of 29 men who underwent traditional routine surgical treatment. The second main group (29 patients) who underwent novel surgical treatment with making urethrocysteoanastomosis based on original method (Patent for invention № 2559588 from 14 Jul 2015 “Method of propylaxis of urinary incontinence after retropubic prostatectomy”). Results . At the moment of the hospital discharge the urine continence was achieved by the 20.7 % (n = 6) patients from the first group and 48.3 % (n = 14) patients from the second group. During the follow-up period in a month after surgery urine continence was maintained by the 37.9 % (n = 11) patients from the first group and 72.4 % (n = 23) patients from the second group, in three months after surgery — 62.0 % (n = 18) patients from the first group and 79.3 % (n = 23) patients from the second group. After the 6 months follow-up period 75.9 % ( n = 22) patients from the first group and 86.2 % (n = 25) patients from the second group maintain urine continence. One-year follow-up period showed urine continence in 89.7 % (n = 26) patients from the first group and 93.1 % (n = 27) patients from the second group Conclusion. The surgical technique developed and introduced into clinical practice made it possible to stabilize urethrocysteoanastomosis, prevent or significantly shorten the incontinence period within the first year after retropubic prostatectomy, and improve the quality of life of patients.

The paper addresses the effect of a new fatty acid elongase 6 (ELOVL6) inhibitor on the migration of breast cancer cells (estrogen receptor positive MCF7 cells and estrogen receptor negative MDA-MB-231 cells) and expression of genes associated with the epithelial-mesenchymal transition, the first stage of tumor metastasis. It was shown that inhibition of the synthesis of C18 fatty acids does not change the migration activity or expression of transcription factors regulating the epithelial-mesenchymal transition. At the same time, the inhibition of ELOVL6 resulted in overexpression of genes associated with breast cancer development and metastasis in vivo (EGFR, CASP4 and VEGFA).

Background. The approach to the management of prostate cancer with lymph node metastases has recently moved towards aggressive multimodal treatment with the use of the most rational combinations that are currently available.Objective: to assess the efficacy and tolerability of chemohormonal therapy (CHT) in patients with high-risk and very high-risk prostate cancer.Materials and methods. An open prospective clinical trial evaluating the efficacy and tolerability of neoadjuvant and adjuvant CHT in patients with high-risk and very high-risk prostate cancer was initiated in 2016 at the P.A. Herzen Moscow Oncology Research Institute. Patient recruitment is still ongoing.A total of 64 patients with high-risk and very high-risk prostate cancer (сT3N0–T3N+М0, prostate specific antigen (PSA) ≥20 ng/mL, and Gleason score of 8–10) were recruited since July 2016. All patients were examined prior to treatment initiation and after 3 and 6 courses of therapy. The examination included pelvic magnetic resonance imaging, ultrasound imaging of the abdominal cavity and retroperitoneal space, transrectal ultrasound imaging, and chest radiography or computed tomography. Serum PSA level was evaluated before each course of therapy. Bone scintigraphy was performed before treatment and after its completion. Study participants were divided into two groups. Group A included patients that initially underwent surgical treatment and then 6 courses of CHT no later than 6 weeks after surgery: docetaxel 75 mg/m2 given intravenously on day 1 of a 21-day cycle and oral prednisolone 10 mg/day. Patients also received hormonal therapy with luteinizing hormone-releasing hormone analogue (aLHRH) given in depot injections every 28 days.Group B included patients that initially received 6 courses of CHT: docetaxel 75 mg/m2 given intravenously on day 1 of a 21-day cycle and oral prednisolone 10 mg/day. After that, patients underwent radical prostatectomy with pelvic lymphadenectomy no later than 4 weeks after the completion of chemotherapy. Patients also received hormonal therapy with aLHRH given in depot injections every 28 days. The total treatment duration was 6 months.Results. The group of adjuvant CHT included 24 patients with high-risk prostate cancer (T3b–4N+М0 with at least 5 regional lymph node metastases detected by morphological examination of surgical specimens). All patients had Gleason score 8–10 tumors. Mean age of patients was 63.0 ± 7.7 years (range: 46–72 years). In total, all patients received 142 courses of CHT. By the time of publishing this article, 23 (96 %) of patients completed their treatment.The group of neoadjuvant CHT included 40 patients with very high-risk prostate cancer (T3b–4N+М0 with metastases to pelvic and retroperitoneal lymph nodes detected by instrumental examination). All patients had Gleason score 8–10 tumors. Mean age of patients was 61.0± 6.4 years (range: 43–69 years). In total, all patients received 236 courses of CHT. By the time of publishing this article, 36 (90 %) of patients completed their treatment. Thirty-five patients (87 %) underwent radical prostatectomy with extensive pelvic and paraaortic lymphadenectomy. Routine pathological examination demonstrated that all patients had signs of tumor destruction. Thirty-three participants (94 %) had grade II therapeutic pathomorphosis, whereas 2 patients (6 %) had grade III therapeutic pathomorphosis.Median PSA relapse-free survival (PSA-RFS) rate in the neoadjuvant CHT group was 10 months. Serum PSA of 0.1 ng/mL 1 month postoperatively correlated with longer RFS (р = 0.04). Biochemical relapse (PSA level >0.2 ng/mL) was observed in 6 patients (15 %) from this group. Later these patients received hormonal therapy with aLHRH. Median PSA-RFS in the adjuvant CHT group was 11 months.The main adverse events in the two groups were hematological toxicity, observed in 24 patients (34.29 %), and gastrointestinal toxicity, observed in 9 patients (12.86 %) (diarrhea (n = 6) and stomatitis (n = 3)). Only grade I–II toxicity was registered so far. Two patients (3.1 %) had febrile neutropenia, which required cytostatic dose reduction by 20 %. Relatively good tolerability and acceptable quality of life allowed the vast majority of patients to be treated on an outpatient basis.Conclusion. So far, we can make only a preliminary conclusion that adjuvant and neoadjuvant CHT is a promising treatment strategy for high-risk and very high-risk prostate cancer.

Over the last 10 years, the capacities of second-line systemic therapy for metastatic renal cell carcinoma (mRCC) changed significantly. Targeted therapy is a standard treatment for patients with mRCC. However, the choice of therapeutic agents for such patients remains challenging. In the absence of reliable prognostic biomarkers, physicians can use only the results of randomized clinical trials and their own routine experience with targeted drugs when choosing a regimen of second-line therapy. The article discusses the current situation with second-line therapy with the three new options available for patients with mRCC. It also contains a case report, describing our successful experience of treatment a female patient that received 6 variants of chemotherapy with good effect during 89 months after the diagnosis.

Men with nonmetastatic, castration-resistant prostate cancer and a rapidly rising prostate-specific antigen level are at high risk for metastasis. Until recently there was no standard of treatment for this category of patients. A total of 1401 patients with nonmetastatic, castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less underwent randomization to double-blind, phase III PROSPER trial. Patients were continuing androgen-deprivation therapy in combination with enzalutamide (at a dose of 160 mg) or placebo once daily. The median metastasis-free survival was 36.6 months in the enzalutamide group versus 14.7 months in the placebo group. Enzalutamide treatment resulted in a 71 % lower risk of radiographic progression or death than did placebo (hazard ratio 0.29; 95 % confidence interval 0.24 to 0.35; p

Bladder cancer is one of the most common malignant diseases involving the urinary system. Accurate prediction of the disease course and outcome is crucial for choosing an appropriate treatment strategy in these patients. Currently, there are several prognostic models for predicting non-muscle invasive bladder cancer outcomes. The scoring systems developed by the European Organization for Research and Treatment of Cancer (EORTC) and the Spanish Urological Club for Oncological Treatment (CUETO) are the most widely used prognostic models for bladder cancer. Despite the undeniable merits of these scales, they need to be supplemented. Since the prognostic score has a direct impact on the treatment strategy, intensity and costs of postoperative follow-up, and outcome, its accuracy should be higher than it is now. Identifying the additional parameters that would increase the robustness of these models is one of the major challenges for researchers.The molecular and genetic characteristics of the tumor, that can be estimated after the first surgery, are probably the best candidates for this role. The main limitation of these prognostic models lies in the fact that they assess only morphological properties of the tumor, while the most important molecular characteristics are neglected. These scoring systems do not evaluate clinical factors, concomitant diseases, and iatrogenic complications occurring during the treatment of relapses. The assessment of molecular mechanisms and clinical characteristics underlying the development of non-muscle-invasive bladder cancer as well as identification of key molecular markers, that could complement the currently existing risk assessment models, are the most important goals for researchers dealing with bladder cancer. It will significantly improve predictive capabilities of these models, ensuring the choice of an optimal treatment strategy.

The review is devoted to loop-mediated isothermal amplification (LAMP) – a novel molecular diagnostic method that has recently become increasingly popular. Unlike polymerase chain reaction, LAMP does not require thermal cycling; DNA or RNA amplification occurs at a constant temperature (about 65 °C) with 4 or 6 primers. This is a fast, highly-sensitive, and highly specific method, which does not require expensive equipment, where visual detection of the reaction products is performed by the unaided eye. LAMP is successfully used for the diagnosis of multiple viruses, bacteria, and other pathogens (including those in food). Moreover, it can be applied for the detection of singlenucleotide polymorphisms. Recently, a modified LAMP assay – one-step nucleic acid amplification (OSNA) – was validated for metastasis detection. OSNA was demonstrated to have almost the same sensitivity and specificity as standard diagnostic methods (sometimes even higher). Particular attention is paid to the mechanism of LAMP, primer design, and diagnostics of cancer using OSNA.

Renal cell carcinoma (RCC) is one of the most common genitourinary malignancies worldwide. Approximately 25–30 % of newly diagnosed patients have metastatic RCC (mRCC), whereas in 20–30 % of cases, dissemination occurs after radical surgical treatment. The development of targeted and immunooncological agents in recent years significantly increased survival in patients with mRCC. However, clinicians faced a problem of choosing an optimal therapeutic regimen to achieve maximum effectiveness of the treatment. This article discusses the choice of second-line drugs for mRCC, advantages of axitinib and its optimal dosage, and efficacy of sunitinib depending on the disease prognosis.

During metastatic growth, cells of solid tumors undergo phenotypical changes related to epithelial-mesenchymal transition. Epithelial-mesenchymal transition is regarded as a potential target for prospective antitumor drugs. Fluorescent reporter systems for evaluation of the expression of markers of epithelial and mesenchymal status (E- and N-cadherins) were created. The described approaches can be used for creation of analogous reporter systems.

Background. Lymph node metastases in prostate cancer (PC) are a negative prognostic factor. Non-invasive methods for their diagnostics are of primary importance. Objectives are identification of miRNA markers of lymph node metastases in plasma of PC patients and investigation of changes in primary tumors transcriptomes and plasma miRNA profiles during metastasis. Materials and methods. Plasma of 20 PC patients (10 with pN0M0 and 10 with pN1M0 stage) were collected and plasma miRNA expression was profiled on GeneChip miRNA 4.0 arrays (Affymetrix, USA). Target genes were searched for miRNAs with significant expression difference between pN0M0 and pN1M0 groups (fold change ≥2; p

Background. Enzalutamide, an androgen receptor inhibitor that blocks multiple steps in the androgen receptor signaling pathway, is approved for patients with metastatic castration-resistant prostate cancer (CRPC). Since the phase III (AFFIRM) pivotal trial did not include Russia patients, this phase II study (NCT02124668) was performed to establish the safety of enzalutamide in patients with progressive CRPC previously treated with docetaxel-based chemotherapy in the Eastern European patients population, including the Russia. Objective: to study safety of enzalutamide in patients with progressive CRPC previously treated with docetaxel-based chemotherapy from Eastern European, including the Russia. Materials and methods . This phase II, multicenter, single-arm, open-label study was conducted at 2 sites in Russia and 2 sites in Georgia. Patients had on going androgen deprivation therapy with a gonadotropin-releasing hormone analogue (agonist or antagonist) or had a prior surgical or chiectomy. Patients completed visits on day 1, week 5, week 13 and subsequently every 12 weeks until they were discontinued from the study. The safety of enzalutamide was assessed through evaluations of adverse events (AEs), serious AEs, blood pressure, heart rate, electrocardiography and laboratory measurements. Results. Thirty patients were enrolled and received enzalutamide treatment (mean age 67.5 years (59–80 years)). Median treatment duration was 271 days (3–968 days). By the end of the study, a total of 23 (76.7 %) patients experienced 68 treatment-emergent AEs (TEAEs). The most frequently reported TEAEs (reported in ≥10 % of patients) were fatigue (n = 7 (23.3 %)), asthenia (n = 6 (20.0 %)), bone pain, metastatic pain, prostatic specific antigen increase from baseline (n = 4 (13.3 %) each) and malignant neoplasm progression (n = 3 (10.0 %)). Most TEAEs were Grade 1 or Grade 2 in severity (35 and 14 events respectively, of a total of 68 AEs). The most frequently reported Grade 3 or higher TEAEs were asthenia (n = 5 (16.7 %)) and bone pain (n = 3 (10.0 %)). Enzalutamide-related TEAEs were experienced by 7 (23.3 %) patients and consisted of the following: fatigue in 3 patients; asthenia in 2 patients; and supraventricular extrasystoles, dizziness, headache, insomnia, pollakiuria and alopecia in 1 patient, each. Six (20.0 %) patients experienced 13 serious TEAEs. The most common serious TEAE was malignant neoplasm progression (n = 3 (1 %)) due to disease progression; all others were single events. Three (10.0 %) patients had died due to serious TEAEs that occurred during the study (2 of prostate cancer progression and 1 of cardiopulmonary and liver failure). No patients experienced an enzalutamide-related Grade 3 or higher TEAEs, an enzalutamide-related serious AEs or an enzalutamide-related TEAEs leading to permanent discontinuation. No notable changes from baseline in clinical laboratory parameters or clinically meaningful abnormalities in vital signs, physical examinations, or electrocardiography were found. No cases of seizures were reported. Conclusion. In this study, enzalutamide in the Eastern European patient population, including the Russia, had a safety profile consistent with that reported in previous enzalutamide studies and no new safety signals were observed.

Brachytherapy is one of the methods of radiotherapy allowing to deliver a highly effective radiation dose to a tumor through a minimally invasive intervention. Depending on the source, brachytherapy can be low- and high-energy. The article describes the main stages of development of prostate cancer brachytherapy both in Russia and abroad. The main methods of brachytherapy used in modern medicine are described. References to recommendations of the leading radiological organizations on low-energy brachytherapy are provided. The main indications and counterindications for brachytherapy for treatment of prostate cancer using low-energy sources are described. Summary data on the effectiveness of the method depending on prostate cancer prognosis are presented. The results of using low-energy brachytherapy at the branches of the National Medical Research Center of Radiology of the Ministry of Health of Russia are described.

Urinary bladder cancer is a fairly common pathology in the structure of cancer morbidity, both in the world and in the Russian Federation, especially in elderly patients. As is well known, the 5-year survival and disease-free survival rates directly correlate with the stage of the tumor process, which determines the significance of an adequate assessment of the distribution of tumors for planning treatment approach. This article provides an overview of scientific studies on imaging techniques that are used for preoperatively staging of urinary bladder cancer. Currently, the most interesting is multiparametric-MRI, which has a number of advantages over other imaging methods including: non-invasiveness, high tissue and spatial visualization and the absence of ionizing radiation. The appearance of this method contributed to an increase in diagnostic effectiveness in assessing the distribution of urinary bladder cancer. However, there are a number of unresolved issues related to errors in interpreting the depth of invasion and evaluation of regional lymphatic outflow, which require detailed study and analysis.

We performed genome-wide transcriptome meta-analysis of prostate cancer samples after radical prostatectomy of patients without lymph node metastasis. Significant associations were determined between expression of platelet-derived growth factor alpha and beta genes (PDGFRA and PDGFRB) and probability and time of onset of biochemical recurrence.

Background. The highest rate of incontinence after radical prostatectomy (RP) is observed in the first 2–6 months after surgery. In order to decrease the period of incontinence, virous surgical methods aimed at preservation and reconstruction of structures participating in the mechanism of urine retention has been developed and improved. The study objective is to evaluate effectiveness of an original method of formation of an urethral anastomosis in the early continence recovery. Materials and methods. Data on 126 patients who underwent retropubic RP were analyzed. Depending on the method of urethral anastomosis formation, patients were divided into 2 groups: in the 1 st group (n = 52) the patients underwent PR with urethra suspension m. levator ani, in the 2 nd (n = 74) – standard RP. In the 1 st group, 6 ligatures were applied to the anterior and posterior urethra walls: at the 12 and 6 hour projections through the mucosa, submucosa, and smooth muscle; at the 10, 2, 4, and 8 hour projections – more laterally with capture of the m. levator ani medial margins. Continence recovery was evaluated on days 1, 7, and 14 after urinary catheter removal and then at days 30, 90, 180, and 365 after RP. The criteria of continence were absence of urine leakage at rest and during physical activity and a necessity of using a safety liner. Results. There weren’t any significant differences at day 1 after urinary catheter removal between the two groups (р > 0.05). In the 1 st group, continence values at days 30, 90, and 180 after RP were significantly higher (57.7, 69.2, and 71.1 %, respectively) compared to the 2 nd group (35.1, 41.9, and 51.3 %, respectively) (р

Hormone therapy of metastatic prostate cancer (mPC) has been the “golden standard” of treatment since 1941. However, survival rates in patients with this pathology have remained low. Based on the results of newer studies, early start of docetaxel chemotherapy or antiandrogen abiraterone therapy in combination with standard hormone therapy allows to significantly increase survival of patients with mPC. In this review, data from these studies and advisability of docetaxel and abiraterone at the 1st line therapy of mPC are discussed.

The problem concerning the prediction of the aggressive status of prostate cancer (PCa) is examined on the basis of preoperative data. This problem is solved using data on 360 patients with the established (aggressive or indolent) postoperative status of the disease. The collection of factors containing five informative indicators of prediction (from primarily accessible sixteen) is revealed and employed to create the diagnostic index used to predict the aggressive PCa status. In compliance with cross-validation data, the prognostic algorithm enables us to find the group involving 55% of patients with an aggressive status in the absence of patients with an indolent PCa status. The three-class prediction algorithm making it possible to ascertain whether any patient belongs to the group with the low, high, or uncertain risk of the aggressive disease stage is proposed.

Objective: to assess safety, responses rate and duration, progression-free and overall survival in patients with advanced urothelial carcinoma receiving vinflunine as second-line therapy in routine clinical practice, after additional patient recruitment.Materials and methods. This retrospective observational multicenter study included medical data of 34 patients with verified advanced urothelial carcinoma receiving vinflunine for tumor progression after first-line chemotherapy in 11 Russian clinical centers from March 23, 2013 to June 3, 2017. The median age of the patients was 60 (44–81) years. ECOG performance status was 0 in 2 (5.9 %), ECOG 1 – in 21 (61.7 %), ECOG 2 – in 9 (26.5 %), and ECOG 3 – in 2 (5.9 %) patients. Visceral metastases were present in 14 (41.2 %), non-visceral – in 20 (58.8 %) cases. Anemia was recorded in 20 (58.8 %) patients. According to Bellmunt scale 2 (5.9 %) patients had none risk factors, 6 (17.6 %) had 1 risk factor, 18 (52.9 %) and 8 (23.5 %) had 2 and 3 risk factors, respectively. Initial vinflunine dosage was 320 mg/m2 in 6 (17.6 %) patients, 280 mg/m2 in 22 (64.8 %) or 250 mg/m2 in 6 (17.6 %). Patient received a median of 4 (1–10) cycles of therapy.Results. Adverse events (AE) were recorded in 33 (97.1 %) cases. The most frequent were general (70.6 %), hematologic (58.8 %), and gastrointestinal AE (41.1 %). Most AE were grades I–II and well-controlled. There were no deaths caused by adverse events. The best response was assessed as complete in 1 (2.9 %), partial – in 5 (14.7 %), stabilization – in 19 (55.9 %), and progression – in 9 (26.5 %) of the 34 patients. Complete response duration was 9.0 months, median partial response duration was 8.0 months (95 % confidence interval (CI) 5.5–13.0); median stabilization duration – 3.5 months (95 % CI 0.7–12.8). Median progression-free and overall survival were 3.9 (95 % CI 3.5‒4.3) and 6.4 (95 % CI 0.1–17.0) months, respectively. Univariate analysis indicated that the low somatic ECOG status and the initial vinflunine dosage of 250 mg/m2 had adverse impact on overall survival.Conclusion. The efficacy and safety of vinflunine as second-line therapy for first-line chemotherapy-resistant advanced urothelial carcinoma in unselected patients are similar to the results of Phase III randomized trial and early results of the Russian observational study.

Introduction . Prostate cancer (PCa) is one of the common oncological diseases in men. Expression of the PCA3 gene in urine is currently used as a molecular genetic marker of PCa. Objective: to comparative analysis of the PCA3 expression in urine sediments and exosomes for the determination of the biomaterial, which allows detecting the PCA3 expression in more efficient manner. Materials and methods. The 12 patients with different stages of PCa and 8 control samples were examined. Results. The diagnostic accuracy of the PCA3 gene expression analysis in this cohort exceeded 90 %. We had not obtained significant differences in the sensitivity and specificity of the PCA3 hyperexpression in the urine sediments compared with exosomes. This result indicates in favor to using urine sediment for the PCA3 analysis as a biomaterial with less time-consuming sample preparation, although the possible advantage of exosomes for the analysis of the expression marker panels requires further studies.

Purpose. To evaluate pharmacokinetics, pharmacodynamics, safety, immunogenicity and efficacy of intravenous infusions of BCD-100 (JSC “BIOCAD”, Russia) in increasing doses. Patients (materials) and methods. Patients with advanced malignant tumors of various localizations without severe somatic pathology were consistently included in cohorts receiving the BCD-100 drug in monotherapy at different doses (0.3, 1.0, 3.0 and 10 mg/kg) every 2 weeks for at least 85 days. Safety, pharmacokinetics, pharmacodynamics, immunogenicity and efficacy of the therapy were assessed. Results. 15 patients were included in the study. The vast majority of adverse events were represented by deviations in the results of laboratory tests of 1-2 grade, there was only one confirmed case of dose-limiting toxicity (autoimmune thyroiditis of 2 grade). Pharmaco kinetic parameters were standard for drug based on monoclonal antibodies of class IgG1. The saturation of PD-1 receptors by BCD-100 was high (90-100%) at all dose levels. 1 partial response to antitumor therapy and 3 stabilization cases according to irRC criteria were registered. conclusion. BCD-100 demonstrated a favorable profile of safety and immunogenicity, expected pharmacokinetic parameters allowing the drug to be administered once every 2 or 3 weeks, high pharmacodynamic parameters and the presence of antitumor activity.

A comparative analysis of the results of diagnosis of cancer metastases in the lymph nodes using a method of one-step nucleic acids amplification (OSNA) and morphological methods was performed. Comparable sensitivity and specificity of OSNA and histological examination of a lymph node were observed.