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Background. In the JAVELIN Bladder 100 trial, 1st line maintenance with avelumab in combination with best supportive care significantly increased (9.2 months) overall survival compared to best supportive care in patients with locally advanced or metastatic urothelial cancer without progression after 1st line platinum-based chemotherapy: 29.7 months versus 20.5 months, respectively. Trial results led to inclusion of avelumab into the international guidelines as a standard of care with the highest level of evidence. Combined therapy with avelumab + axitinib in patients with previously untreated metastatic renal cell carcinoma showed higher progression-free survival and objective response rate compared to sunitinib in all IMDC (International Metastatic Renal Cancer Database Consortium) groups. Avelumab + axitinib is one of the immuno-oncology combinations with proven effectiveness for progression-free survival and objective response rate.Aim. To evaluate the effectiveness of avelumab in treatment of oncological urological diseases in routine clinical practice. Materials and methods. At the N.A. Lopatkin Scientific Research Institute of Urology and Interventional Radiology - branch of the National Medical Research Radiology Center, 12 patients with locally advanced inoperable and metastatic urothelial cancer without progression after 1st line platinum-based chemotherapy in combination with gemcitabine received maintenance avelumab therapy. Median follow-up was 10 months. Primary endpoints were overall survival from the start of avelumab maintenance therapy and safety.Combined therapy with avelumab + axitinib was administered in 18 patients with metastatic renal cell carcinoma. Median follow-up was 9 (3-16) months. Overall survival, progression-free survival, response rate and safety in the overall population and according to IMDC groups were evaluated.Results. At data cut-off (March 2023) with median follow-up of 10 months, overall survival was 100 %, progression-free survival was 66.7 % (among patients who received more than 3 infusions - 100 %). Progression-free survival was higher in patients with tumors of the lower urinary tract compared to upper (72.5 % versus 60 %), complete response to induction platinum-based chemotherapy compared to partial response and stable disease (100 % versus 66.7 %) and presence of metastases in the lymph nodes only compared to visceral and bone metastases (100 % versus 66.7 %). Adverse events were observed in 4 (66.7 %) patients.Among 18 patients who received avelumab + axitinib, complete response was observed in 2 (11.1 %) patients, partial response in 6 (33.3 %) patients, stable disease in 9 (50 %) patients, disease progression in 1 (5.6 %) patient. Response to therapy was observed in patients of all prognosis groups; for large (>5 cm) metastases in the lungs, soft tissues, lymph nodes and bones response was observed 3 months after treatment start. Overall survival for this follow-up duration was 100 %, progression-free survival was 96.4 ± 11.2 %. Adverse events were observed in 8 (44.4 %) patients, and in 6 (75 %) of them they were grade I—II and did not require infusion regimen correction or axitinib dose reduction.Conclusion. Avelumab maintenance therapy in the 1st line is the standard of care for patients with locally advanced and metastatic urothelial cancer without disease progression during 1st line platinum-based chemotherapy. Maintenance therapy allows to achieve better overall survival and progression-free survival irrespective of the choice of platinum regimen (cisplatin or carboplatin), response to platinum-based chemotherapy, number of chemotherapy cycles, tumor localization and advancement.Experience of the N.A. Lopatkin Scientific Research Institute of Urology and Interventional Radiology confirms results of the JAVELIN Bladder 100 trial on the effectiveness of avelumab maintenance therapy in routine clinical practice. Combination drug therapy with avelumab and axitinib in patients with metastatic renal cell carcinoma is an effective and safe treatment method which allows to achieve fast objective response and has good tolerability in patients irrespective of IMDC group or metastasis location. Effectiveness and favorable safety profile of avelumab + axitinib combination were proven in the context of routine clinical practice.

Background. Prostate cancer patients with a positive resection margin after radical prostatectomy are at risk of developing local recurrence. This risk should be carefully estimated in order to choose an optimal management strategy.Aim. To develop a nomogram to predict the risk of local recurrence in patients with a positive resection margin using the data on patients who have undergone surgery.Materials and methods. Routine pathomorphological examination of surgical specimens from 2255 patients with clinically significant local and locally advanced prostate cancer revealed 364 cases of positive resection margin. Statistical analysis allowed us to identify the most significant prognostic factors. Using selected preoperative factors and a mathematical model, we created a nomogram to predict local recurrence in patients with a positive resection margin.Results. Our nomogram had an accuracy of 93% (area under the ROC curve (AUC) 0.9392; p Conclusion. Our mathematical model and the nomogram based on it are highly accurate for predicting local recurrence and can therefore be used for choosing an optimal management strategy.

Background. Prostate cancer is one of the most common malignant tumors in men. Tailored treatment approaches to metastatic castration-resistant prostate cancer based on identification of specific biomarkers have been introduced only recently. So far, the Food and Drug Administration has approved two drugs (olaparib and rucaparib) targeting the DNA repair genes.Aim. To assess the frequency of mutations in the DNA repair genes in the Russian population.Materials and methods. The article uses data from two centers (National Medical Research Radiological Center and A.I. Kryzhanovsky Krasnoyarsk Regional Clinical Oncological Dispensary) which included the largest numbers of patients in the largest Russian multicenter prospective trial ADAM. We performed genotyping of all valid tumor samples from 113 patients with metastatic castration-resistant prostate cancer to identify clinically significant mutations in the DNA repair genes.Results. Next-generation sequencing demonstrated that 27 patients (23.9 %) had clinically significant mutations in DNA repair genes were, including ATM in 6 (5.3 %), BRCA1 in 5 (4.4 %), BRCA2 in 4 (3.5 %), CDK12 in 3 (2.6 %), CHEK2 in 2 (1.8 %), PALB2 in 2 (1.8 %), BRIP1 in 2 (1.8 %), BARD1 in 1 (0.9 %), RAD51B in 1 (0.9 %), and RAD51C in 1 patient (0.9 %).Conclusion. Identification of mutations in the DNA repair genes should become a routine procedure, since a new treatment approach to metastatic castration-resistant prostate cancer is now being introduced.

Background. Prostate cancer (PCa) is an actual disease and a frequent oncological pathology in men. The main methods of radical treatment of patients with PCa are radical prostatectomy and radiation therapy. Radical prostatectomy s the most commonly used method of therapy in patients with localized PCa. Adjuvant hormone therapy after surgical treatment is the standard method of therapy in patients with the presence of lymph node metastases. At the same time, the standard approach of treatment of patients with metastatic PCa is combination therapy with medical (using of analogues or antagonists of luteinizing hormone-releasing hormone (LHRH) or surgical castration in combination with chemotherapy with docetaxel or new generation antiandrogens (enzalutamide or apalutamide)). Numerous studies have demonstrated the importance of achieving minimum testosterone levels at all stages of drug therapy in patients with PCa. It has also been shown that the use of LHRH analogues may be less effective to the use of LHRH antagonists (degarelix) in relation to the effectiveness of testosterone suppression. Thus, conducting a study aimed at studying the effectiveness of testosterone suppression using LHRH antagonists in various clinical situations and patient populations in real clinical practice is a very actual task.Aim. To evaluate the effectiveness and safety of castration therapy using degarelix in real clinical practice and in various clinical situations.Materials and methods. The object of an observational non-interventional study was 132 patients with PCa from 13 cancer centers of Russian Federation who were treated with LHRH antagonist degarelix. The study was non-interventional (observational), retrospectively-prospective, open multicenter and not randomized. In accordance with the design of the study, depending on the clinical situation, patients were divided into 3 groups: group A (n = 52; 39.4 %) – patients with primary metastatic hormone-sensitive PCa, who were shown to undergo combined drug treatment with castration therapy as one of the components; group B (n = 43; 32.6 %) – patients, who underwent combined hormonal and radiation treatment (ADT + radiation therapy); group C (n = 37; 28 %) – patients who underwent surgical treatment (radical prostatectomy with extended PLND) with the presence of metastases in the lymph nodes identified by the results of a morphological examination (pN1).Results and conclusion. As a result of a non-interventional observational study, high efficacy of androgen-deprivation therapy with the use of degarelix was demonstrated in relation to the suppression of testosterone and PSA in patients with primary metastatic and locally advanced PCa in various clinical situations, as well as low toxicity and satisfactory tolerability of this variant of hormonal treatment.

Leiomyosarcoma of the bladder is an extremely aggressive malignant tumor. Today in the world literature there are a little more than 200 described cases of bladder leiomyosarcoma. In all the cases described, the neoplasm originated from the proper muscle layer of the bladder. In this work, we present a unique clinical case – bladder leiomyosarcoma originating from the muscular elements of the bladder mucosa.

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 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.

Currently, due to the dynamic development of surgical technologies, indications for organ-sparing treatment of kidney cancer are expanding. Acute kidney injury is a serious complication that leads to chronic kidney disease, increased postoperative mortality, deterioration of long-term functional outcomes, and increased hospitalization. At present, it is known that even a slight damage to kidneys or their impairment, presented by a decreased urine output and change in blood biochemical parameters, entails serious clinical consequences and is associated with a poor prognosis. Damaging factors, when the kidney is exposed, initially induce molecular changes, which entail the production of certain biomarkers, and only after that clinical aspects of kidney damage develop. The causes of acute kidney injury can be different, from specific renal disorders (acute interstitial nephritis, vascular and glomerular lesions, prerenal azotemia, obstructive disorders) to toxic damages, direct trauma and surgical treatment. The development of acute renal injury in the postoperative period is a serious complication of the surgical treatment of kidney disease, and, according to various authors, the frequency of its occurrence varies from 5.5 % to 34 %. An active study of this problem made it possible to find specific biomarkers that give the possibility to predict and diagnose acute renal injury in the early stages, to optimize the treatment strategy, to reduce the incidence of postoperative complications, and to shorten the period of postoperative rehabilitation. Currently, the most studied of acute kidney injury (AKI) biomarkers are cystatin C, neutrophil gelatinase-associated lipocalin‑2 (NGAL), hepatic protein L-FABP, KIM‑1 (Kidney injury molecule‑1), Interleukin – 18. Further study of AKI biomarkers will make it possible to determine the most significant ones for subsequent use in everyday practice

Background. Prostate cancer is currently one of the most challenging problems in urological oncology due to its constantly increasing incidence and mortality in Russia. Surgery remains one of the most radical treatment options for patients with localized and locally advanced prostate cancer of any risk. Multiple studies have compared long-term and functional outcomes of surgeries performed using different surgical approaches. All studies have demonstrated similar long-term and functional outcomes of open, laparoscopic, and robot-assisted surgeries. Objective: to review the existing literature on this problem and analyze outcomes of surgical treatment in patients who had undergone open or laparoscopic prostatectomy in one of three federal centers of the National Medical Research Radiology Center.Materials and methods. This retrospective study included 2,772 patients with localized and locally advanced prostate cancer who had undergone surgery in one of the three federal centers.Results. We evaluated short-term and long-term outcomes of laparoscopic and open radical retropubic prostatectomy (RRP) performed at three federal centers of the National Medical Research Radiology Center. We found that laparoscopic RRP was associated with a longer surgery, lower blood loss, and fewer lymph nodes removed compared to open RRP. Long-term oncological and functional outcomes (prostate-specific antigen relapse-free survival, time to urination recovery) did not significantly differ between patients who had laparoscopic or open RRP.Conclusion. Both open and laparoscopic RRP are equally effective surgical methods for patients with localized and locally advanced prostate cancer.

Prostate cancer (PCa) is one of the most common malignant tumor in men. Significant advances have been made in the early detection and treatment of localized PCa, but metastatic castration-resistant PCa (mCRPC) remains one of the most challenging problems to treat in oncology. To improve treatment outcomes for patients at this stage of the disease, it is necessary to develop personalized therapy options based on the definition of biological predictors. In mCRPC, mutations in DNA repair genes are detected in ~23 % of patients with mCRPC. Detection of these mutations in patients with PCa has important clinical relevance. PCa with mutations in DNA repair genes may be sensitive to poly(ADP-ribose)-polymerase (PARP) inhibitors. Several studies II and III phase have demonstrated the effectiveness of PARP inhibitors with a high objective response rate in the treatment of mCRPC in patients with mutations in the DNA repair genes, which is definitely a more personalized approach to treatment. Identification of hereditary mutations in DNA repair genes is an important prognostic factor for the proband's relatives (for both men and women), which can later be used for genetic counseling of patients and the application of strategies to reduce the risk of malignant diseases.

Androgen deprivation therapy (ADT) is one of the main treatments for patients with locally advanced and metastatic prostate cancer. ADT decreases the level of testosterone. Despite the development of new effective drugs in recent years, luteinizing gonadotropin-releasing hormone agonists are frequently administered as ADT. One of the most commonly used first-line drugs is triptorelin (Diferelin®). In Russia, patients usually receive slow-release triptorelin administered once every month or every 3 months (intramuscular injections) and once every 3 months (subcutaneous injections); the result of using different dosage forms is comparable. Triptorelin effectively keeps serum testosterone level below 20 ng/dL, thereby increasing the time to development of castration-resistant prostate cancer, overall survival of patients receiving combination treatment with radiotherapy, and reduces the severity of symptoms from the lower urinary tract. Triptorelin has a good safety profile and is generally well tolerated by patients.

Background. Prostate cancer (PCa) remains one of the most relevant problems in oncology. The incidence and mortality of PCa is constantly rising in Russia. The rate of annual increase in the number of new PCa cases is the highest among all malignancies in Russia and reaches 87.7 % over 10 years (from 2008 to 2018). Approximately one-third of patients have high-risk PCa. This article analyzes the outcomes of surgical treatment in high-risk PCa patients. Objective : to evaluate survival of patients with high-risk PCa after surgical treatment and analyze prognostic factors affecting survival. Materials and methods. This retrospective study included 1507 high-risk PCa patients who have undergone surgical treatment at P.A. Herzen Moscow Oncology Research Institute. Study participants were divided into groups to assess the effect of preoperative prognostic factors on patient survival after surgery. The following factors were analyzed: level of prostate specific antigen >20 ng/mL, Gleason score 8—10, and сТ3—4 clinical stage. Results . Median follow-up time was 58 months. The five-year biochemical relapse-free survival rate in the general group was 57.4 %; five-year overall and cancer-specific survival rates were 94.4 % and 97.7 %, respectively. The incidence of biochemical relapses and survival rates depended on the presence and number of risk factors in the groups studied (p

Objective: to assess the potential clinical significance of KIM-1 (kidney injury molecule 1) as a urinological marker for kidney cancer.Materials and methods. An enzyme-linked immunosorbent assay was used to assess urinary KIM-1 (uKIM-1 — kidney injury molecule 1) levels in 67 patients with renal cell carcinoma (RCC) and 36 healthy volunteers (a control group).Results. Both in patients and in healthy individuals, uKIM-1 levels were age independent. A difference between mean uKIM-1 values in RCC patients (2.4 ± 0.2 ng/ml) and the control group (0.7 ± 0.1 ng/ml) was statistically significant (p Conclusion. This study demonstrates that uKIM-1 can be attributed to potentially significant urine tumor-associated markers of RCC.

Prostate cancer is one of the most actual oncourological diseases because of the persisting high rates of morbidity and mortality from this pathology. More than 1 100 000 new cases of this pathology are registered in the world every year. The incidence of prostate cancer in the Russian Federation continues to increase steadily. Despite the success in early detection of this disease, primarily due to the introduction of diagnostics with the use of a specific prostatic antigen, the frequency of detection of primary metastatic cancer of the prostate gland remains high and is about 20%. Metastatic castration-resistant prostate cancer is an extremely heterogeneous disease with an unfavorable prognosis in most of these patients, which requires a differentiated approach when prescribing therapy in each case. Despite the standard approach to prescribing chemotherapy as one of the main methods of drug treatment, the method of hormonal therapy of the second line using drugs aimed at the androgenic mechanism of cellular proliferation regulation is an effective and less toxic option. A fundamentally different mechanism of action has a new drug hormonal therapy of the second line enzalutamide, which is able to selectively block androgen receptors and disturb the translocation of the signal from the receptor into the cell and the cell nucleus. A number of large randomized trials that studied the effectiveness of this drug have allowed to register it for clinical use, including in our country. The article presents a review of the literature on the use of enzalutamide in patients with metastatic castration-refractory prostate cancer, as well as a description of the clinical case of the use of this drug in real practice.

This article presents a clinical case demonsratinga high metastatic potential of clear cell renal cell carcinoma combined with atypical metastases to breast and paranasal sinuses. The prevalence of metastatic lesions to the breast and paranasal sinuses in various malignant tumors depending on their morphological forms is analyzed. The authors present an analysis of data published for the last 30 years. The optimal diagnostic algorithms to detect the progression of renal cell carcinoma and to evaluate the effectiveness of the treatment are considered.

Prostate cancer (PC) is the most pressing oncourological pathology due to a steady increase in morbidity and mortality from this pathology in the Russian Federation. The detection frequency of the common forms of the disease remains high. The combined chemo-hormonal therapy is the main method of treatment of metastatic prostate cancer. The refractoriness of the tumour to the ongoing castration therapy is an inevitable stage of the course of the disease in all patients receiving androgen deprivation therapy. However, castration therapy aimed at reducing endogenous testosterone in this cohort of patients should be continued. Eligard is one of the most studied drugs to conduct the drug castration therapy in patients with prostate cancer, which efficacy has been proven in numerous clinical studies in both continuous and intermittent mode using depot forms of various durations of action. The article presents a review of clinical studies that assessed the efficacy of Eligard therapy in different regimens and with the use of depot forms of various duration, which demonstrated equal effectiveness of such forms.

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.

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

Objective: to investigate the safety of vinflunine, the rate and duration of its treatment response, progression-free and overall survival rates in patients receiving this drug in routine clinical practice for first-line chemotherapy (CT) – resistant disseminated transitional cell carcinoma of the urinary tract. Materials and methods. This retrospective observational multicenter study included data on 25 patients with verified disseminated transitional cell carcinoma of the urinary tract who took vinflunine for tumor progression after first-line CT performed in 11 Russian clinical centers in 23 March 2013 to 26 June 2016. The median age of the patients was 60 (44‒81) years. Their baseline somatic status was rated as ECOG 0 in 1 (4.0 %) patient, ECOG 1 in 13 (52.0 %) patients, EGOG 2 in 9 (36.0 %), and ECOG 3 in 2 (8.0 %). The most common sites of tumor foci were bones (n = 14, 56.0 %), lymph nodes of different groups (n = 14; 56.0 %), and lung (n = 9; 36.0 %). Results. Adverse reactions were recorded in 24 (96.0 %) cases. The most common types of toxicity were asthenia (n = 19; 76.0 %), anemia (n = 18; 72.0 %), neutropenia (n = 13; 52 %), and nausea (n = 12; 48.0 %). Most adverse events were grades I–II and well controlled. There were no deaths due to adverse events. The best treatment response was regarded as partial in 6 (24.0 %) patients; stabilization and progression were observed in 10 (40.0 %) and 9 (36.0 %) patients, respectively. The median duration of partial response was 5.1 (95 % confidence interval (CI), 0.6–15.0) months; that of stabilization was 3.4 (95 % CI, 1.2–6.3) months. In all the 25 cases, the median progression-free and overall survival rates were 3.7 (95 % CI, 2.1‒5.3) and 6.5 (95 % CI, 5.2‒7.8) months, respectively. The somatic status was a predictor of overall survival (p < 0.0001). Conclusion. The efficacy and safety of vinflunine in second-line therapy for first-line CT-resistant disseminated transitional cell carcinoma of the urinary tract in unselected patients agree with those previously observed in Phase III randomized trial.

Renal cell carcinoma (RCC) takes one of the leading places in the world incidence among malignant tumors of the genitourinary system. Metastatic renal cell cancer (mRCC) is detected in about 25–30 % of primary patients. 10 targeted immuno-oncology drugs for the treatment of mRCC were registered and approved for use from 2005 till the present time. Rapid growth of therapeutic options of mRCC treatment has created a problem for practicing oncologists and urologists as well as necessity to understand the principles and consistent optimization of targeted therapy to maximize the effectiveness of each treatment line. The article discusses issues of the correct choice of first-line targeted drugs, optimal dosing of sunitinib and aksitinib, alternative modes and alternating use of sunitinib, as well as the influence of objective response and hypertension, which developed on the background of the targeted therapy on the effectiveness of treatment.

Prostate cancer (PC) is one of the most actual problems of modern oncourology. Hormone therapy (HT) using medical castration is the main method of treatment of patients with metastatic PC. HT with usage of the new class of drugs that block the receptors for luteinizing hormone releasing hormone (LHRH) is a promising and effective method of castration therapy that has a number of significant advantages over the use of analogues LHRH. This article presents a review of studies that compared the effectiveness and side effects of HT using antagonists and analogues LHRH.

Clear cell renal cell carcinoma (ccRCC) is a common urologic malignancy. Understanding of the transcriptional regulation of oncogenes and tumor suppressor genes involved is critical for the development of the treatments for renal tumors. Using ccRCC subdivision of the TCGA dataset, we identified NR0B2 encoding orphan nuclear receptor as a tumor suppressor candidate in renal tissue. In independent cohort of primary renal tumors, quantitative PCR experiments confirmed significant suppression of NR0B2 mRNA in 86% of ccRCC samples studied. In 80% of these cases, we detected the hypermethylation of the NR0B2 pro-moter region. These results suggest that NR0B2 is a tumor suppressor gene in ccRCC, and that the hypermethylation of promoter region is the main mechanism of its downregulation.

Clear cell renal cell carcinoma (ccRCC) is a common oncourological disease with a high mortality level. The incidence of this type of cancer is constantly increasing, while molecular mechanisms involved in the disease initiation and progression remain far from being fully understood. A problem of the search for novel markers is crucial for improvement of diagnosis and therapy of ccRCC. We have previously found that the disease is characterized by increased expression of the NETO2 gene. In the present study, we showed that isoform 1 (NM_018092.4) makes the main contribution to the upregulation of this gene. Using original CrossHub software, "The Cancer Genome Atlas" (TCGA) project data were analyzed to identify possible mechanisms of NETO2 gene activation in ccRCC. The absence of significant contribution of methylation to the increase of mRNA level of the gene was observed. At the same time, a number of genes encoding transcription factors, which could potentially regulate the expression of NETO2 in ccRCC, were identified. Three such genes (MYCBP, JMY, and SAP30) were selected for the further analysis of their mRNA levels in a set of ccRCC samples with quantitative PCR. We showed a significant increase in mRNA level of one of the examined genes, SAP30, and revealed its positive correlation with NETO2 gene expression. Thus, upregulation of NETO2 gene is first stipulated by the isoform 1 (NM_018092.4), and the probable mechanism of its activation is associated with the increased expression of SAP30 transcription factor.

Glycolysis activation is one of the main features of energy metabolism in cancer cells that is associated with the increase in glycolytic enzyme synthesis, primarily, hexokinases (HKs), in many types of tumors. Conversely, in colorectal cancer (CRC) the decrease in the expression of HK2 gene, which encodes one of the key rate-limiting enzyme of glycolysis, was revealed, thus, the study of the mechanisms of its inhibition in CRC is of particular interest. To search for potential microRNAs, inhibiting the expression of HK2 in CRC, we have performed the analysis of data from "The Cancer Genome Atlas" (TCGA) and five microRNA-mRNA target interaction databases (TargetScan, DIANA microT, mirSVR (miRanda), PicTar, and miRTarBase) using original CrossHub software. Seven microRNAs containing binding site on mRNA HK2, which expression is negatively correlated with HK2 expression, were selected for further analysis. The expression levels of these microRNAs and mRNA HK2 were estimated by quantitative PCR on a set of CRC samples. It has been shown, that the expression of three microRNAs (miR-9-5p, -98-5p, and -199-5p) was increased and correlated negatively with mRNA level of HK2 gene. Thus, downregulation of HK2 gene may be caused by its negative regulation through microRNAs miR-9-5p, -98-5p, and -199-5p.

One of the hallmarks of cancer is the change of energy metabolism, mainly activation of glycolysis that occurs even at early stages of tumorigenesis. The glycolysis activation can be caused by overexpression of hexokinases, primarily HK1 and HK2. Colorectal cancer, which takes the third place in the cancer morbidity and mortality rates worldwide, is believed to be accompanied with overexpression of HK2, which is .considered a marker of poor prognosis. With the use of the developed CrossHub tool, we performed the analysis of the Cancer Genome Atlas RNA-Sequencing data, which, on the contrary, revealed the prevalence of the down-regulation of HK2 gene and only slight expression alterations in HK1 gene. The Cancer Genome Atlas is the largest resource in the field of molecular oncology that accumulated genomic, transcriptomic and methylomic data for thousands of sample of more than 20 cancers. The transcriptome analysis data for colorectal cancer (283 tumor samples and 41 matched normal samples) were in accord with the results of further qPCR expression level evaluation. Up-regulation of HK1 and HK2 genes was observed only in a part of samples: 12% for HK1 and 30% for HK2. At the same time, the HK2 mRNA level decrease was shown in 50% of cases. Correlation analysis revealed the consistency in HK1 and HK2 expression alterations (Spearman's rank correlation coefficient r(s) = 0.43, p0.01), that could be explained by common deregulation mechanisms of these genes in colorectal tumors. The HK3 expression level was significantly increased in 60% of samples. Most likely, just hexokinase 3 contributes significantly to the activation of glycolysis in colorectal cancer.

The major problem in prostate cancer treatment is the development of drug resistance and especially important, cross-resistance. The mechanisms of drug resistance, which are divided into ligand-dependent (requiring the presence of androgens in the cell) and independent (not requiring the presence of androgens) are reviewed. The mechanisms are mainly represented with mutations of the androgen receptor and expression of aberrant constitutively active splice variants, as well as up-regulation of genes involved in androgens synthesis.

Cytoreductive nephrectomy as an independent option in patients with metastatic renal cell carcinoma (mRCC) cannot be considered as the only effective method, with rare exception, of a few patients with solitary metastases. Cytoreductive nephrectomy is now part of a multimodal approach encompassing surgical treatment and systemic drug therapy. Many retrospective and two prospective studies have demonstrated that it is expedient to perform cytoreductive nephrectomy. Immunotherapy should not be used as preoperatively in the era of cytokine therapy for mRCC due to that fact that it has no impact on primary tumor. In the current targeted therapy era, many investigators have concentrated attention on the role of neoadjuvant targeted therapy for the treatment of patients with both localized and locally advanced mRCC. The potential benefits of neoadjuvant therapy for localized and locally advanced RCC include to make surgery easier and to increase the possibility of organsparing treatment, by decreasing the stage of primary tumor and the size of tumors. The possible potential advantages of neoadjuvant targeted therapy in patients with mRCC include prompt initiation of necessary systemic therapy; identification of patients with primary refractory tumors; and a preoperative reduction in the stage of primary tumor. Numerous retrospective and some prospective phase II studies have shown that neoadjuvant targeted therapy in patients with localized and locally advanced RCC is possible and tolerable and surgical treatment after neoadjuvant targeted therapy is safe and executable with a low incidence of complications. If neoadjuvant therapy is to be performed, it should be done within 2–4 months before surgery. Sorafenib and sunitinib are now most tested and suitable for neoadjuvant targeted therapy. Sorafenib is a more preferred drug due to its shorter half-life and accordingly to the possibility of discontinuing the drug immediately prior to surgery. Unquestionably, elaboration of precise recommendations for neoadjuvant therapy calls for further larger prospective studies estimating progression and survival rates in high-risk patients with localized and locally advanced RCC and in those with mRCC.