Background. Metastasing and degree of differentiation refer to the main clinical characteristics of malignant tumors. Both listed features need an in-depth study that can lead to an understanding of the mechanisms for the occurrence of certain state of cancer cells.

Objective. Studying the processes of metastasis and differentiation of the clear cell renal cell carcinoma (ccRCC) on gene expression.

Materials and methods. The levels of expression of ten genes in 65 paired samples were studied (ccRCC tumor tissue and the normal kidney tissue) by the real-time polymerase chain reaction.

Results. It is shown that the expression of CA9, NDUFA4L2, VWF, IGFBP3, BHLHE41, ANGPTL4 and EGLN3 genes is associated both with the degree of differentiation of the ccRCC and with the metastasis of this tumor. C1QA expression is connected only with metastasis, but does not participate in the process of differentiation of tumor cells. An ambiguous situation with FN1 and CSF1R gene expression is not essential for ccRCC metastasis processes, but may have a certain value for differentiation of cells of this tumor. Low-differentiated tumors have about five times an increased metastasis frequency during the year relative to highly differentiated tumors (odds ratio 4.94). A low correlation of gene expression in tumors with a low degree of differentiation is revealed, as opposed to their high co-expression during tumor progression by TNM classifications.

Conclusion. A significant part of genes substantial for the development of ccRCC is associated with both metastasis and the degree of differentiation of the ccRCC, which is due to the similarity of functional changes that stimulate both of these processes. For low-differentiated tumors the number of genes with correlated expression is less than in high-differentiated tumors. This may be due to disorganization of gene expression.

Objective: to analyze the long-term oncological results of surgical treatment of patients with stage cT1-сТ2аN0M0 renal cell cancer.

Materials and methods. The analysis included 326 patients who underwent partial nephrectomy (PN) in 210 (64.42 %) and radical nephrectomy (RN) - in 116 (35.58 %). Stage cT1a tumors were found in 129 (39.57 %), cT1b - in 149 (45.71 %), cT2a - in 48 (14.72 %) cases. PN and RN for cT1a was performed in 113 (53.81 %) and 16 (13.79 %), for cT1b -in 86 (40.95 %) and 63 (54.31 %), for cT2a - in 11 (5.24 %) and 37 (31.90 %) patients. We used open approach in 5 (1.53 %), laparoscopic in 148 (45.26 %) and robotic in 173 (53.21 %). The median follow-up was 49.9 [26.0; 81.4] months.

Results. In the group of patients with stage cT1a disease, 4 recurrences of the tumor process were revealed (3 local recurrences after PN and 1 after RN). Seven deaths were recorded (4 after PR and 3 after RN). Two deaths occurred due to the progression of kidney cancer (1 after PN and 1 after RN). 5-year disease-free survival after PN and RN was 95.93 ± 2.32 % versus 92.31 ± 7.39 % (p >0.05); 5-year overall survival - 96.48 ± 2.08 % versus 85.56 ± 9.65 % (p >0.05); 5-year cancer-specific survival - 98.33 ± 1.65 % versus 92.25 ± 6.5 % (p >0.05).

In the group of patients with stage cT1b disease, 12 recurrences were revealed (5 after PN and 7 after RN). 14 deaths were recorded (4 after PN and 10 after RN). Four deaths were related to the development of kidney cancer (all after RN). 5-year disease-free survival after PN and RN was 92.97 ± 3.1 % versus 86.99 ± 4.64 % (p >0.05); 5-year overall survival -95.1 ± 2.78 % versus 88.63 ± 4.4 % (p >0.05); 5-year cancer-specific survival - 100 % versus 94.1 ± 3.33 % (p >0,05).

There were no recurrences of the oncological process or deaths after PN in the group of patients with the stage of cT2a disease during four years of follow-up. After RN six recurrences of the oncological process, four deaths (3 of them due to the progression of kidney cancer) were recorded. Thus, the disease-free survival at was 80.57 ± 7.15 %; overall survival - 90.28 ± 5.34 %; cancer-specific survival - 93.63 ± 4.37 %.

Conclusion. PN is the priority treatment for renal cell cancer. Oncological results of nephron-sparing surgery are superior to the results of RN, however, these differences are not reliable and require a longer study.

Background. Since partial nephrectomy and radical nephrectomy demonstrate comparable oncological safety, nephronsparing surgery is the method of choice in patients with stage T1-T2aN0M0 renal cell carcinoma.

Objective: to compare the main perioperative parameters and short-term functional outcomes of treatment for localized stage cT1aN0M0 and cT1b-T2aN0M0 renal cell carcinoma.

Materials and methods. A total of 148 laparoscopic partial nephrectomies were performed at N.I. Pirogov City Clinical Hospital No. 1, N.I. Pirogov Russian National Research Medical University between 2016 and 2020. Study participants were divided into two groups. Group 1 included patients with stage cT1aN0M0 tumors (n = 89; 60.1 %), whereas group 2 comprised patients with stage T1b-T2aN0M0 tumors (n = 59; 39.9 %).

Results. The duration of surgery was 120 min (range: 90-150 min) in group 1 and 145 min (range: 120-170 min) in group 2 (p = 0.001). The median time of warm ischemia was 13 min (range: 7-17) and 15 min (range: 12-19 min) in groups 1 and 2, respectively (p = 0.002). Seven individuals from group 1 (7.9 %) and 12 individuals from group 2 (22.3 %) had their pelvicalyceal system lanced. The median glomerular filtration rate calculated using the MDRD (Modification of Diet in Renal Disease) formula was 56.4 mL/min/1.73 m² in group 1 and 54.3 mL/min/1.73 m² in group 2 (p = 0.252). Three patients in group 1 (3.4 %) had positive resection margin. The median follow-up time was 21 months.

Conclusion. Nephron-sparing surgeries are an acceptable option for patients with stage cT1b-T2aN0M0 tumors in terms of their oncological and functional safety. Tumors exceeding 4 cm were associated with an increased risk of disease progression.

Background. Vasopressin, in cooperative interaction with angiotensin II, participates in cardiovascular regulation and it increases in arterial hypertension. In addition, vasopressin is involved in tumorigenesis through angiogenesis by stimulating protein synthesis in endothelial cells, induction of endothelin-1, influencing cell proliferation, and stimulating growth factors through VIA receptors in the kidneys. To assess the content of vasopressin, a measurement of copeptin, its precursor, produced in an equimolar ratio, is used.

Objective: to determine the content of serum copeptin and to reveal correlations with the indices of the renin-angiotensin system in the tumor and blood serum in patients with localized kidney cancer (КС) with arterial hypertension (AH).

Materials and methods. The inclusion criteria for the study were initially diagnosed localized KC T1N0M0 without special treatment, age less than 75 years, essential AH of I—II degree without treatment, controlled by angiotensin-converting enzyme inhibitors (ACEi). All patients were divided into groups: patients with KC (n = 42); KC + AH without treatment (n = 31); KC + AH + ACEi (n = 32). Serum levels of copeptin and angiotensin I, II, 1-7 and angiotensin-converting enzyme, angiotensin-converting enzyme 2 were determined by ELISA. Also, the level of components of the renin-angiotensin system was assessed in tumor tissue samples obtained by robotic-assisted kidney resection.

Results and conclusion. In patients of the KC + AH group, the median of the indicator is statistically significantly higher than in the group of healthy donors (2.4 times at p <0.05). In the group KC + AH + ACEi, a decrease in the content of the studied indicator was found in comparison with the norm by 1.2 times (at p <0.05). It was found that the content of copeptin in the tumor less than 4 cm in comparison with the size of 4-7 cm is significantly lower (KC p = 0.045, KC + AH p = 0.067 and KC + AH + ACEi p = 0.036). Correlation analysis showed direct significant links between high density between the levels of copeptin and angiotensin II in the tumor and blood, and moderate tightness with tumor and serum levels of angiotensin (1-7). Multiple regression analysis revealed that the most significant factors that have a positive effect on the concentration of serum copeptin are the content of angiotensin II in the tumor and blood serum, the tumor concentration of angiotensin (1-7) and angiotensin-converting enzyme 2, as well as the level of systolic blood pressure (p <0.05).

Background. MicroRNAs (miRNAs) circulating in plasma are promising markers for the diagnosis of malignant tumors, including prostate cancer. However, the existing techniques used for their detection fail to ensure sufficient diagnostic accuracy. One of the possible ways to improve it is to isolate membrane nano-sized extracellular vesicles (nsEVs) secreted by prostate cells. Presumably, the analysis of miRNAs originating from this prostate-specific fraction of nsEVs more accurately reflects the process of prostate cancer development and has a greater diagnostic potential.  Objective: to develop the method of miRNA isolation from the prostate-specific fraction of plasma nsEVs and to evaluate its performance characteristics.

Materials and methods. Prostate-specific membrane antigen (PSMA) was used as a prostate-specific marker of nsEVs. The total population of plasma nsEVs was isolated using a two-phase polymer system. To isolate PSMA-positive (PSMA⁽⁺⁾) nsEVs, we used superparamagnetic particles with PSMA-binding DNA aptamer immobilized on their surface. The efficacy of PSMA⁽⁺⁾ nsEV isolation was assessed using flow cytometry and dot-blotting. RNA from nsEVs was isolated using proteolysis; miRNA analysis was performed using reverse transcription polymerase chain reaction. Plasma samples collected from patients with prostate cancer (n = 33) and healthy donors (controls) (n = 30) were used to evaluate the diagnostic parameters of the method.

Results. We developed the method of PSMA⁽⁺⁾ nsEV isolation from plasma and estimated its performance characteristics. We found that measurement of potential miRNA markers in PSMA⁽⁺⁾ nsEVs was more effective than its measurement in the entire nsEV population and could distinguish between patients with prostate cancer and controls.

Conclusion. The new technique of PSMA⁽⁺⁾ nsEV isolation can be used for the development of novel diagnostic methods for the diagnosis of prostate cancer.

Background. Prostate cancer is the most common malignant condition among oncological diseases of the genitourinary tract, which occupies the second place in male mortality from malignant neoplasms. At the same time, population of patients with prostate cancer is heterogeneous: in some patients, the disease does not require active treatment, while in others it progresses rapidly with the formation of metastatic castration-resistant prostate cancer. Therefore, the search for new predictive markers remains relevant.

Objective. Analysis of the prognostic significance of the loss of heterozygosity of PTEN, RB1, TP53, BRCA1 and BRCA2 genes in patients with localized and locally advanced prostate cancer.

Materials and methods. The study included 52 patients with prostate cancer, 31 (59.6 %) of whom had a localized form (T1-2N0M0), and 21 (40.4 %) - locally advanced (T3a-bN0/1M0). All patients underwent radical prostatectomy, followed by genotyping of postoperative and biopsy specimens to determine genetic alterations in the studied genes. Detection of deletions in the studied genes was carried out using the method of multiplex ligation-dependent probe amplification.

Results. In 13 (25.0 %) patients in the postoperative specimen was detected deletion of PTEN gene, in 6 (11.5 %) - deletion of RB1 gene, and in 1 (1.9 %) - deletion of BRCA2 gene. At the same time, patients with loss of PTEN heterozygosity were more likely to have perineural invasion (p = 0.01) and lymph node involvement (p = 0.0003). Deletion of RB1 gene is associated with more frequent detection of high-grade tumors (p = 0.013), cribriform growth component (p = 0.002), and invasion of the periprostatic tissue (p = 0.005).

Conclusion. Detection of loss of heterozygosity of PTEN and RB1 genes is a promising tool for clarifying the prognosis of the disease, which in the future will allow more accurately stratify patients into risk groups for biochemical relapse.

Background. Radiation therapy is one of the leading treatments for early and late stage prostate cancer. Radiation therapy is one of the leading treatments for early and late stage prostate cancer. The significant frequency of prostate cancer progression after radiation therapy makes it relevant to study the molecular mechanisms of the development of radioresistance, to identify prognostic markers of its development.

Objective: identification and analysis of the mechanism of action of microRNAs regulating radioresistance of prostate cancer cells on the model of the androgen-independent DU145 cell line.

Materials and methods. We used human prostate adenocarcinoma cell lines: DU145-hormone-independent prostate cancer cell line and DU145-RR - its radioresistant variant. Differential microRNA expression was measured in cultured DU145 and DU145-RR cells 1, 8 days after a single gamma irradiation at a dose of 4 Gy. To analyze the differential expression of microRNAs in the initial and radioresistant variants of DU145 cells, the HiSeq 2000 platform (Illumina Inc., USA) was used. The miRBase v.21 database was used to identify microRNAs. The miRTarbase 7.0 and KEGG PATHWAY databases were used for bioinformatic analysis

Results. The results of the study showed that the aberrant expression of miR-101-3p, -148a-3p, -21-3p, -532-5p, -92a-3p in DU145-RR cells upregulated compared to that in DU145 cells, and miR-125b-5p, -23a-3p, -424-3p - downregulated. It has been shown that the role of these microRNAs is associated with the provision of functional interaction between DNA methyltransferases, the transcriptional regulator of the proto-oncogenic protein Myc, and PTEN phosphatase in the regulation of the activity of MAPK and PI3K protein kinase signaling cascades. Constitutive activation of these cascades leads to an increase in cell survival, migration, proliferation, and growth.

Conclusion. A wide range of target genes and a significant change in the expression profiles of microRNAs in various conditions, including the transition of malignant cells to a radioresistant status, makes microRNAs promising prognostic markers of radioresistance in prostate cancer.

Background. It seems advisable to investigate the feasibility of radiation therapy combined with hormone therapy to treat locally advanced prostate cancer. Combination of two ways to deliver ionizing radiation doses enables us to elevate a total tumor dose and to reduce radiation exposure to critical organs. However, the feasibility of combinatorial radiation therapy (CRT) in prostate cancer patients with seminal vesicle invasion remains insufficiently investigated. The number of studies focusing on this problem is still extremely small.

Objective of this study is to evaluate the efficacy and toxicity of radiation therapy combined with hormone therapy for prostate cancer with seminal vesicle invasion.

Materials and methods. From April 2016 to April 2020, 52 patients with prostate cancer (cT3bN0) received CRT at the clinic of the A.F. Tsyb Medical Radiological Research Center. The median patient follow-up was 29.7 months (from 11.9 to 58.4 months). The mean age of patients was 65.7 years. The initial mean level of PSA was 28.7 ng/ml. Fifty (96.2 %) patients were given radiation therapy together with hormone therapy.

Results. The tolerability of CRT appeared satisfactory. Grade I acute radiation-induced reactions of the urinary tract occurred in 13 (25 %) patients; grade II ones - in 2 (3.8 %) patients. Grade I acute radiation-induced reactions of the gastrointestinal tract occurred in 11 (21.5 %) patients; grade II ones - in 1 (1.9 %) patient. Grade I late complications of the urinary tract were noted in 4 (7.7 %) patients; grade II ones - in 2 (3.8 %) patients. Grade I late complications of the gastrointestinal tract were noted in 2 (3.8 %) patients; grade II ones - in 3 (5.8 %) patients.

The three-year cancer-specific survival rate was 97 %; the overall survival rate was 83 %. Eight (15.4 %) patients showed prostate cancer progression. Five (9.6 %) patients experienced cancer recurrence in the form of distant bone metastases. In 1 (1.9 %) patient, disease recurrence was associated with involvement of regional lymphatic collectors and distant inguinal lymph node metastases. Local recurrence was noted in 1 (1.9 %) patient. One (1.9 %) patient developed loco-regional recurrence with distant metastasis to bones. The three-year recurrence-free survival rate was 75.6 %.

Conclusion. Our study demonstrates that CRT is highly effective in prostate cancer (cT3bN0) treatment while having an acceptable level of complications.

Background. Prostate cancer (PCa) patients often develop recurrent disease after radical surgery. A tool that can accurately predict the risk of disease progression in the population of Russian patients will be very helpful to choose an optimal treatment strategy and prevent possible recurrence.

Objective: to analyze preoperative and postoperative prognostic factors for PCa progression and identify the most significant of them.

Materials and methods. This study included 2,255 patients with localized and locally advanced PCa who underwent radical surgery. We constructed nomograms for predicting the risk of disease progression after surgery using mathematical models.

Results. We created nomograms for predicting the risk of biochemical recurrence and probability of relapse-free survival by the level of prostate specific antigen (PSA) in patients with no lymph node metastases (pN0) according to the results of morphological examination and in patients with lymph node metastases (pN1). The accuracy of nomograms reached 71 % (area under the ROC curve (AUC) 0.7119) and 76 % (AUC 0.7617), respectively.

Conclusion. The nomograms demonstrated high accuracy of prognosis and can be used in the population of Russian patients.

This article aims to give an up-to-date review of studies on the diagnosis and treatment of patients with bladder cancer (BCa). We emphasize that the assessment of treatment and prognosis using specific markers is a promising method. However, clinical data currently outpace the results of molecular testing. Patients with luminal BCa demonstrate worse response to pharmacotherapy than those with other BCa types. The implementation of new drugs such as avelumab, enfortumab, and new drug combinations into clinical practice raised hopes to improve treatment outcomes of patients with locally advanced and metastatic bladder cancer. The development of new pharmacotherapy and immunotherapy regimens will improve treatment outcomes. We describe the experience of some foreign countries with the treatment and outpatient follow-up of patients after radical cystectomy. The article also contains the guidelines by the European Association of Urology on the treatment of patients with urinary tract cancers during the COVID-19 pandemic.

Advances in immuno-oncology in the treatment of metastatic urothelial cancer have overturned current perspectives on the treatment of this type of tumor. The success of using Immune checkpoint inhibitors in metastatic urothelial cancer raised the question of effectiveness of immunotherapy added to standard first-line chemotherapy. This review presents data coming from actual studies examining chemotherapy and immunotherapy in urothelial cancer, or a combination of these methods. Ongoing and planned clinical studies should help identify the optimal sequencing, feasibility of combination, and best duration of treatment with checkpoint inhibitors in urothelial cancer.

This review outlines current trends in applying texture analysis for the treatment of patients with renal parenchyma tumor. The prospects of using radiomics in the diagnosis and treatment of patients with renal cell carcinoma are presented.

This article presents a modern possibilities and future path of prostate-specific membrane antigen (PSMA) radiopharmacuticals labeled by ^99mTc, that is the most popular isotope using in conventional nuclear medicine. The main advantages and disadvantages of SPECT/CT with these radiopharmaceuticals in different phases of prostate cancer continuum have been analyzed. Results of research diagnostic sensitivity of ^99mTc-PSMA SPECT/CT including comparison with ⁶⁸Ga-PSMA PET/CT and conventional modality such as MRI and bone scan are presented. The prerequisites of application ^99mTc-labeled PSMA ligands in PSMA-guided surgery, methodology of PSMA-guided surgery and foreign authors application experience are presented in this article too.

The formation of primary multiple malignant neoplasms, such as breast cancer and prostate cancer, in one patient is a rather rare combination. Treatment and diagnostic strategies in such cases require a multidisciplinary approach. Currently, there are no approved recommendations for the management of patients with a combination of these diseases. This manuscript presents a clinical case of diagnosis and treatment of breast and prostate cancer in one patient.

In western European countries prostate cancer is one of the most common malignant disease among male population. Due to innovations in molecular genetics research technology over recent years genetic features of etiology and pathogenesis of prostate cancer have been discovered and this helped to distinguish people with high risk of prostate cancer development. Hereditary forms of malignant tumors occupy a special position due to association with mutations in BRCA1/2 gene in a group of patients with prostate cancer. The most important part of examination of patients with malignant diseases is medico-genetic counseling. It helps to reveal the hereditary of the disease. The detection of germinal mutations in BRCA1/2 gene helps to personify diagnostic measures for primary prophylaxis and treatment of prostate cancer.

Here is a case of one patient with hereditary feature of prostate cancer with a mutation in BRCA1 gene. It is important to note that revealing mutations in BRSA gene helps to early diagnose malignant neoplasms. Screening measures to reveal germinal mutations in healthy population can improve early detection of such malignant diseases as breast cancer, prostate cancer and other malignant neoplasms.

The classification of cystic renal masses according to computed tomography data, which allows to stratify them depending on the risk of malignancy, was created by M.A. Bosniak in 1986 and modified in 1994. Various groups of researchers have carried out meta-analysis based on the results of applying the proposed classification during the time that has passed since the publication of the last version. Taking into account the information received, which revealed a number of limitations and disadvantages of the previously used method for systematizing renal cystic masses, as well as in connection with the development of medical imaging methods, updated diagnostic algorithms were formulated, which served as the basis for the Bosniak 2019 classification. It is expected that the use of Bosniak 2019 will optimize stratification renal lesions of the cystic structure and reduce the number of removed benign tumors, can be used as a basis for the future research to further improve the classification and its congruence with the requirements of clinical specialists.

Research into the physiology of active substances in the 50s of the last century led to the discovery of new peptides, which were named releasing factors, or releasing hormones. The nature of these substances was studied by Roger Guillemin and Andrew Victor Schally. Within a few years, the luteinizing hormone-releasing hormone was isolated, sequenced and synthesized. This discovery laid the ground for modern research on the hypothalamus. Results of animal studies were quickly translated to humans and found their use in clinical practice. The American researcher Rosalyn Sussman Yalow used radioisotopes to measure the volume of circulating blood and to study the distribution of serum proteins in body tissues, as well as to diagnose diseases of the thyroid. Subsequently, a radioimmunological method was developed, including the use of radioactive agents to track various substances in the blood plasma and other tissues. In 1977, Rosalyn Yalow was awarded half of the Nobel Prize in Physiology and Medicine “for the development of radio-immunological methods for the determination of peptide hormones”. Another part of this award was shared by Roger Guillemin and Andrew Schally for a similar research on brain hormones related to “the production of peptide hormones in the brain”. Doctors around the world use the discoveries of these outstanding scientists to improve the quality of life and increase the life expectancy in millions of patients with prostate cancer.