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Purpose: an assessment of efficacy and safety of cabozantinib in unselected patients with metastatic renal cell carcinoma in the first and subsequent lines of therapy.Materials and methods. Russian multicenter observational study included 92 consecutive patients with morphologically verified metastatic renal cell carcinoma treated with cabozantinib (60 mg/d) in 16 Russian centers. Median age of the patients was 56 (19-79) years, a male-to-female ratio - 3:1. At the start of cabozantinib therapy 27.2 % of patients had ECOG PS 2. Most common histological type of kidney cancer was clear-cell RCC (90.2 %). Most patients were diagnosed with synchronous (71.7 %) multiple metastases (60.9 %). Previous nephrectomy was performed in 87.0 % of cases. Prognosis according to International Metastatic Renal Cancer Database Consortium (IMDC) score was assessed as favorable in 5.4 %, intermediate - in 58.7 % and poor - in 35.9 % patients. Cabozantinib as the first-line therapy was administered in 9 (9.8 %), following 1-5 lines of systemic treatment - in 83 (90.2 %) cases. Median follow-up was 11 (2.3-44.5) months.Results. In patients, receiving cabozantinib as the first-line therapy, objective response rate was 66.7 %, tumor control was reached in 100 % of cases. Median time to the objective response was 2.6 (1.9-3.6) months, median objective response duration - 13.2 (6.2-21.5) months. Median progression-free survival (PFS) and overall survival (OS) were not reached, 6- and 12-months PFS was 77.8 % and 77.8 %, 6- and 12-months OS - 88.9 % and 88.9 % respectively. Cabozantinib as the second and subsequent lines of therapy provided objective response rate of 34.9 %, tumor control rate - 97.6 %. Median time to the objective response was 2.5 (1.8-4.1) months, median objective response duration - 12.6 (5.5-27.3) months. Median PFS was not reached (6- and 12-months PFS - 92.5 % and 73.1 % respectively), median OS was 32.6 months (6- and 12-months OS - 97.4 % and 80.8 % respectively). Any adverse events (AE) developed in 88.8 %, AE grade III-IV - in 32.6 % of cases. Most frequent AE grade III-IV included arterial hypertension (18.5 %), diarrhea (6.5 %) and palmar-plantar erythrodysesthesia (6.5 %). Unacceptable toxicity demanded treatment cancellation in 2.2 %, therapy interruption - in 16.3 % and dose reduction - in 30.4 % of patients.Conclusion. Cabozantinib as the first and subsequent lines of therapy for metastatic renal cell carcinoma patients in the real world practice demonstrated high efficacy and better tolerability comparing with population assigned for cabozantinib monotherapy in the randomized phase II-III trials.

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. Currently, treatment tactics for oligometastatic renal cancer are a debatable topic due to relatively localized process and high risk of skeletal-related events (SRE). Therefore, the effect of treatment on quality of life of these patients is an important subject.Aim. To evaluate quality of life of patients with solitary renal cancer metastases in the bones before and after surgical treatment in combination with targeted therapy and without it.Materials and methods. The study included 64 patients with solitary bone metastases and symptoms of SRE. The patients underwent surgical treatment due to solitary bone metastases of renal cancer in combination with targeted therapy (1st group; n = 25) and without targeted therapy (2nd group; n = 39). The effects of surgical treatment on patients’ condition were evaluated using the EORTC-QLQ-C30 questionnaire.Results. In the 1st group, no statistically significant differences were shown for 8 of 30 indicators of the EORTC-QLQ-C30 questionnaire: restrictions in daily activities, dyspnea, appetite loss, nausea, vomiting, fatigue, tension, financial difficulties. The rest of the indicators showed statistically significant shift toward improvement. In the 2nd group, 7 of 30 indicators did not show statistically significant differences: restrictions in daily activities, dyspnea, sleep disorders, appetite loss, diarrhea, tension, financial difficulties. The rest of the questionnaire points also showed improvement (especially in decreased pain syndrome). In patients of the 2nd group before and after surgery, need for rest, fatigue, appetite loss and restrictions in performing work were more pronounced than in the 1st group. Additionally, after surgery patients of this group required more time in the chair and had more frequent diarrhea, while prior to surgery they complained more of nausea and fatigue. The last 2 parameters evaluating overall quality of life were higher in the 1st group before and after surgery which shows better baseline condition of these patients which was not affected by the treatment.Conclusion. Therefore, surgical treatment of renal cancer bone metastases both in combination with targeted therapy and without it significantly improves quality of life according to the results of quality of life evaluation using the EORTC-QLQ-C30 questionnaire in patients of the studied groups.

Currently, combination immunotarget therapy is the treatment standard for patients with disseminated carcinoma of the renal parenchyma. Simultaneous inhibition of immune checkpoints of programmed cell death 1 (PD-1)/PD-L1 and VEGF/VEGFR signal transduction showed synergistic antitumor effect both in preclinical models and clinical practice.The article presents the results of phase III CLEAR (NCT02811861) trial.In the phase III CLEAR (NCT02811861) trial, 1069 patients with renal cell carcinoma with clear-cell component who previously did not receive systemic antitumor therapy were randomized 1:1:1 in groups of lenvatinib (20 mg/day per os) + pembrolizumab (200 mg intravenously once in 21 days), combination lenvatinib (18 mg/day per os) + everolimus (5 mg/day per os), and sunitinib (50 mg/day per os for 4 weeks with 2-week interval). The groups included 355, 357, and 357 patients respectively. Primary endpoint was progression-free survival (PFS) controlled by expertise of an independent central committee per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v.1.1). Additionally, patient overall survival (OS) and drug therapy tolerability were evaluated.Median PFS for lenvatinib with pembrolizumab was significantly higher than for sunitinib (23.9 months vs. 9.2 months; progression hazard ratio (HR) 0.39; 95 % confidence interval (CI) 0.32–0.49; p vs. 9.2 months; HR 0.65; 95 % CI 0.53–0.8; p p = 0.005). No advantages in OS of lenvatinib and everolimus compared to sunitinib were detected (death HR 1.15; 95 % CI 0.88–1.5; p = 0.3). Frequency of grade III and higher adverse events among patients receiving lenvatinib + pembrolizumab, lenvatinib + everolimus, and sunitinib were 82.4, 83.1, and 71.8 %, respectively.Pembrolizumab + lenvatinib combination showed high effectiveness in 1st line treatment of renal cell carcinoma compared to sunitinib per PFS and OS values.

Aim. To improve diagnostics and screening of prostate cancer to ensure early detection of malignant tumors.Materials and methods. We analyzed the population size and structure in the region in 2005–2010. The primary diagnostics of prostate cancer in regional healthcare institutions allowed the detection of locally advanced tumors and generalized cancer. Such diagnostic approaches can produce only accidental diagnosis since they lack proper systematization, organization, and control.Results. We have developed and implemented into clinical practice a long-term Program for Prostate Cancer Early Diagnosis and Screening. It includes a diagnostic algorithm for prostate cancer that was modified for clinical use. Screening starts with the PSA blood test performed annually. Patients with PSA level >10 ng/mL should undergo additional diagnostic procedures. The Program implies active use of currently available information technologies to implement a unified routing scheme for cancer patients, execute measures for early cancer diagnosis, and warrant promptness and reliability of the cancer registry.Conclusion. Implementation of the long-term Program for Prostate Cancer Early Diagnosis and Screening will help to improve prostate cancer diagnosis, and, therefore, treatment outcomes.

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.

Recently, there has been a worldwide increase in the incidence of bladder cancer. Improved morphological diagnostics, increased surgical activity and availability of chemotherapy allowed reducing the one-year mortality rate and increasing the five-year survival rate. However, at the same time, there was a struggle with complications arising after the treatment. According to the world and domestic literature, it is noted that with an increase in life expectancy in patients who underwent radical cystectomy with intestinal urine derivation, an almost twofold increase in the frequency of complications, including the formation of urinary stones, is recorded. Previous studies have shown that about 60 % of the stones identified in this category of patients are infectious, and 40 % formed because of metabolic disorders, which have their own characteristics with different types of urine derivation. In this work, we present an overview of the predisposition for stone formation in patients who underwent cystectomy for musculoinvasive bladder cancer, taking into account the type of urine derivation.

Background. Focal therapies for prostate cancer (PCa) can preserve the quality of life; however, their application is limited by lack of confidence in identifying the exact tumor location.Aim. To evaluate the utility of fusion biopsy for choosing PCa patients eligible for focal therapy with subsequent confirmation by the analysis of radical prostatectomy (RPE) samples.Materials and methods. This study included 122 patients with histologically verified stage Т1–2N0M0 PCa treated in N.A. Lopatkin Research Institute of Urology and Interventional Radiology, a branch of the National Medical Research Radiology Center. Their mean age was 65.2 ± 6.8 years. All patients underwent multiparametric magnetic resonance imaging and fusion biopsy (samples were collected from targeted areas in combination with a standard biopsy), followed by histological examination of biopsy samples and mapping of the affected areas. Twenty-eight patient underwent RPE.Results. Study participants were distributed as follows by their Prostate Imaging Reporting and Data System (PI-RADS) score: 5 points in 23 patients (18.9 %), 4 points in 57 patients (46.7 %), and 3 points in 42 patients (34.4 %). Targeted biopsy revealed cancer in 105 out of 122 patients (86.1 %) in at least one sample. Seventeen targeted biopsy samples were negative. The majority of patients had ISUP (International Society of Urological Pathology) grade 1 (n = 57; 46.8 %) and grade 2 (n = 33; 27.0 %) tumors. Comparison of biopsy findings and results of pathological examination of the removed prostate demonstrated significant discrepancies in the distribution of cases by their ISUP grades. Almost half of the patients (46.8 %) were diagnosed with ISUP grade 1 tumors after biopsy, while the assessment of RPE specimen demonstrated ISUP grade 1 tumors only in 21.4 % of patients. ISUP grade 3 tumors were diagnosed in 16.4 % and 35.7 % of patients using biopsy- and RPE-derived specimens, respectively. The proportions of ISUP grade 2, 4, and 5 tumors were similar with both methods. In 27 out of 28 cases, examination of biopsy- and RPE-derived specimens demonstrated complete agreement in terms of tumor location. Importantly, this study included only patients with histologically confirmed PCa; so we didn’t evaluate the effectiveness of biopsy for cancer diagnosis. Focal therapy could have been considered in 22 out of 28 patients (78.6 %) who underwent RPE. This proportion of focal therapy-eligible patients is almost equal to that identified by fusion biopsy (75.4 %).Conclusion. Multiparametric magnetic resonance imaging in combination with targeted and multifocal prostate biopsy allow precise identification of candidates eligible for focal therapy with a relatively low risk of an erroneous conclusion.

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.

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.

The study objective is to evaluate effectiveness and tolerability of 1st line combination immuno-oncological therapy with nivolumab and ipilimumab in patients with metastatic renal cell carcinoma (mRCC) in clinical practice.Materials and methods. The study included 38 patients with mRCC who received combination immunotherapy between July of 2019 and September of 2021. Median follow-up duration was 8 (2-25) months. Mean age of the patients was 58.3 (20-85) years. Previously 22 (57.9 %) patients underwent surgical treatment. Unfavorable physical status 2-3 per the ECOG scale was observed in 10 (26.3 %) patients. Clear-cell type of renal cell carcinoma was diagnosed in 34 (89.6 %) patients, non-clear-cell types in 4 (10.4 %). Sarcomatoid component in the tumor was detected in 8 (21.0 %) patients. G3-4 mRCC variant was verified in 16 (42.1 %) patients. Poor prognosis per the IMDC (International Metastatic Renal Cell Carcinoma Database Consortium) scale was identified in 16 (42.1 %) patients, intermediate -in 20 (52.6 %) patients. All 4 administrations of combination immunotherapy were received by 29 (76.3 %) patients.Results. For median follow-up duration of 8 (2-25) months, 23 (60.5 %) patients continue treatment, 15 (39.5 %) completed therapy with nivolumab and ipilimumab due to various reasons including progression in 11 (28.9 %), death in 2 (5.3 %), intolerable toxicity in 2 (5.3 %) cases. Median duration of combination immunotherapy was 9 (2-24) months. Subsequent antitumor therapy was administered to 3 (7.9 %) patients. During induction course immune-mediated adverse event (grade III-IV hepatitis) developed in 3 (7.9 %) patients. Adverse events were observed in 81.6 % of patients, including grade III-IV in 23.7 % of patients. Objective response was observed in 44.8 % of cases, complete response in 5.3 % of cases, partial response in 39.5 % of cases; controlled disease was achieved in 84.3 % of patients. Median progression-free survival and overall survival were 8 months.Conclusion. In our study despite large number of patients with poor prognosis and poorly differentiated tumors, 64.0 % of patients are alive and 60.5 % of patients continue treatment without disease progression after 18 months of combination immunotherapy. Progression-free survival was significantly affected by sarcomatoid component in the tumor, number of unfavorable factors per the IMDC scale, best response per RECIST 1.1; overall survival was significantly affected by sarcomatoid component in the tumor, sum of measurable lesions, number of unfavorable factors per the IMDC scale, best response per RECIST 1.1, and presence of symptomatic metastases in the brain.

Objective: to analyze factors affecting relapse-free and overall survival of patients with non-metastatic non-clear cell renal cell carcinoma (nccRCC) after surgical treatment.Materials and methods. This study included 279 (13.62 %) nccRCC patients from the database containing information on 2049 patients with localized and locally advanced renal cell carcinoma (RCC) without distant metastases who underwent surgical treatment in the Department of Urologic Oncology, P.A. Herzen Moscow Oncology Research Institute between 2002 and 2018. Gender ratio was 1.36:1 (161 men (57.7 %) and 118 women (42.3 %)). Median follow-up time was 34.5 months (range: 1-141 months). Patients had undergone either radical nephrectomy (n = 117; 41.9 %) or kidney resection (n = 160; 57.4 %) or radiofrequency thermal ablation (n = 2; 0.7 %). Standard (open) transperitoneal approach was used in 135 patients (48.4 %) patients, whereas 144 (51.6 %) patients were operated on via laparoscopic approach. Postoperative histological examination demonstrated that 110 participants (39.4 %) had chromophobe RCC, while 79 (28.3 %) and 63 (22.6 %) individuals had type 1 and type 2 papillary RCC, respectively. Twenty-seven patients were found to have rare or mixed variants of nccRCC (they were excluded from the analysis due to their relatively small number). Patients were diagnosed with the following stages of cancer: рТ1а (n = 129; 46.2 %), pT1b (n = 72; 25.8 %), рТ2а (n = 18; 6.5 %), pT2b (n = 8; 2.9 %), рТ3а (n = 31; 11.1 %), pT3b (n = 4; 1.4 %), рТ4 (n = 1; 0,4 %), and pN+ (n = 16; 5.7 %).Results and conclusion. 13 patients (4.7 %) were diagnosed progressive disease; 9 patients (3.2 %) died due to nccRCC progression. The highest relapse-free and overall survival rates were registered in the patients with type 1 papillary RCC and chromophobe RCC.Spearman's correlation analysis showed a significant correlation between the risk of disease progression and tumor size (R = 0.23; p

Prostate cancer is an important disease in current oncological urology. Radical treatment of patients with localized and locally advanced prostate cancer, including surgical and radiological treatments, often does not cure patients from this pathology, especially in the group with high risk of disease progression; the risk of biochemical recurrence in this patient group can be up to 40-60 %. Widespread application of radical treatment allowed to significantly increase survival of patients from this group. However, in case of biochemical recurrence, the majority of patients require longterm androgen-depriving therapy for suppression of natural testosterone level. In some of these patients during longterm castration therapy, non-metastatic castration-resistant prostate cancer develops (CRPC) in the absence of signs of radiological disease progression. Results of large randomized trials show the necessity of stratification of these patients in the group with high risk of progression considering short doubling period of prostate-specific antigen and realization of distant metastases. The main therapy concept for this patient group is use of new-generation inhibitors of androgen signal to increase time to CRPC metastases and overall life expectancy. The article presents results of large trials performed in patients with non-metastatic CRPC and characterizes the role of one of the most effective drugs, darolutamide, used for treatment in this patient cohort.

В апреле 2021 г. был опубликован документ, в котором достигнут консенсус относительно того, что в условиях ограниченных ресурсов врачи готовы экономить на диагностике, но не на лечении. В настоящем обзоре представлены главные постулаты лечения неметастатического кастрационно-резистентного рака предстательной железы в условиях ограниченных и безграничных ресурсов, личное мнение и собственный опыт экспертов, принимавших участие в регистрационных протоколах SPA.

Background. Despite the recent amendments to the guidelines for the treatment of metastatic hormone-sensitive prostate cancer (PCa) implying standard use of luteinizing hormone-releasing hormone (LHRH) agonists in combination with chemotherapy or androgen inhibitors, androgen deprivation therapy (ADT) remains an essential component of treatment for advanced PCa. Testosterone target castration level of 20 ng/dL implies routine measurement of testosterone levels along with prostate-specific antigen (PSA) levels during ADT. It is particularly interesting to evaluate the frequency of achieving castration testosterone level in routine clinical practice. Objective: to assess the frequency of achieving castration testosterone level (20 ng/dL) and maintaining it after 6 months of therapy in patients with hormone-sensitive PCa receiving an LHRH agonist for the first time. Materials and methods. In 2019-2020, Russian Society of Cancer Urologists conducted a non-interventional prospective multicenter study (observational program) aimed to evaluate the efficacy of LHRH agonist (including buserelin, goserelin, leuprorelin or triptorelin) in routine clinical practice in Russia. This study involved 39 cancer urologists and 479 patients aged 18 years and older diagnosed with hormone-sensitive PCa, who started their ADT with LHRH agonists for the first time regardless of the disease stage and previous treatment. Patients received hormone therapy with an LHRH agonist for at least 6 months, visiting their doctor every 3 months (visit 1; visit 2: after 3 months; visit 3: after 6 months). Results. Patients received one of the following drugs: leuprorelin (3.75 mg; 7.5 mg; 22.5 mg; 45 mg; n = 225; 47,0 %), goserelin (3.6 mg; 10.8 mg; n = 132; 27.5 %), buserelin (3.75 mg; n = 67; 14.0 %), and triptorelin (3.75 mg; 11.25 mg; n = 55; 11.5 %). Of 479 patients, 186 (38.8 %) received combination treatment with bicalutamide, 12 (2.5 %) with fluta-mide, 54 (11.3 %) with zoledronic acid, and 11 (2.3 %) with denosumab. Among 146 patients with metastatic PCa, a combination of ADT plus docetaxel was administered to 30 participants (20.6 %), ADT plus abiraterone to 8 participants (5.5 %), and ADT plus enzalutamide to 2 participants (1.4 %). After 6 months of therapy, mean PSA level decreased by 94.2 % (from baseline 118.12 ng/mL to 6.87 ng/mL). Mean testosterone level was 19.0 ng/dL (range: 0.029-100 ng/dL). Among 430 patients, the targeted testosterone level 50 ng/dL. The incidence of adverse events was low; most of them were mild. Conclusion. Our findings suggest that not all patients achieve targeted testosterone level of

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.

Objective. The primary endpoint was progression-free survival; secondary endpoints included overall survival, objective response rate and duration, tumor control rate and duration, as well as safety profile of lenvatinib with everolimus in consecutive patients with advanced renal cell carcinoma who had disease progression after targeted antiangiogenic therapy.Materials and methods. This observational study included 129 consecutive patients with metastatic renal cell carcinoma resistant to targeted antiangiogenic therapy. The median age was 60 years; a male to female ratio was 3.1:1. Twenty-seven patients (20.9 %) had ECOG performance status of 2—4. The majority of study participants (n = 127; 98.4 %) had multiple metastases. Tumor lesions were located in >1 organ in 104 cases (80.6 %). The primary tumor was removed in 110 (85.3 %), including 39 (30.2 %) patients undergone cytoreductive surgery. Seventy patients (54.2 %) had earlier received more than one line of therapy. Upon enrollment, there were 13 IMDC favourable-risk patients (10.1 %), 86 IMDC intermediate-risk patients (66.6 %), and 29 IMDC poor-risk patients (22.5 %). In one patient (0.8 %), the IMDC risk was not estimated. All patients received lenvatinib at a dose of 18 mg/day and everolimus at a dose of 5 mg/day. The median follow-up was 10.5 (1—30) months.Results. Median progression-free survival was 14.9 (11.9—17.9) months; overall survival was 19.9 (15.2—24.6) months. The objective response rate was 17.0 % (median duration 9.7 (2.8—16.5) months); tumor control rate was 72.9 % (median duration 10.0 (2.5—17.5) months). Adverse events were observed in 112patients (86.8 %) with grade III—IVadverse events registered in 27participants (20.9 %). Five participants (3.9 %) needed inpatient treatment of adverse events; one patient (0.8 %) died due to adverse events. Adverse events required treatment discontinuation in 4 patients (3.1 %), treatment interruption in 35 patients (27.1 %), and dose reduction in 33 patients (25.6 %).Conclusion. The results of the secondary analysis in the ROSLERCM observational study confirmed the results obtained earlier on the efficacy and safety of the lenvatinib plus everolimus combination in the second- and subsequent-line therapy for advanced renal cell carcinoma resistant to targeted antiangiogenic therapy in consecutive Russian patients.

Background. Intraoperative rectal injury in patients undergoing prostatectomy is a severe complication, worsens the quality of life and leads to social maladjustment.Objective. To develop, substantiate the reproducibility and safety of the technique for the formation of fascial duplication in the elimination of damage to the anterior rectal wall during prostatectomy.Materials and methods. The authors present a description of the technique and their own experience of retropubic prostatectomy with the formation of fascial duplication in the elimination of damage to the anterior rectal wall in 2 patients with prostate cancer. Patients with intermediate risk of recurrence and progression according to the D'Amico index. The observation period is 6 and 11 months.Results. Prostatectomy revealed damage to the anterior rectal wall and destruction of the external longitudinal muscular layer of the rectum. The rectal defect was eliminated according to the original method. The duration of the operation is 160 and 140 min. Intraoperative blood loss 350 and 150 ml. The first bowel movement on the 5th day. Removal of the urethral catheter on day 10. The period of hospitalization was 11 and 14 days, no postoperative mortality was noted. No lethal outcomes were noted.Conclusion. A constructively simple surgical technique for the formation of fascial duplication by local tissues in case of intraoperative injury of the rectum during prostatectomy has been developed and implemented into clinical practice.

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.

In recent decades, due to advances in imaging and improvements in diagnostic algorithms, there has been a tendency to increase the frequency of detection of small renal masses for which nephron-sparing surgery is possible. To predict the potential complexity of partial nephrectomy and to reduce the degree of subjectivity in choosing the volume and method of surgical procedure, different groups of researchers proposed a significant number of concepts for evaluating renal tumours. The R.E.N.A.L. nephrometry score is one of the first but remains relevant and is based on a set of anatomical characteristics. This score allows to classify renal neoplasms in a structured and standardized way. This article presents a method for evaluating the parameters of R.E.N.A.L. nephrometry score, as well as a brief literature review of its prognostic significance.

The incidence of mesenchymal bladder tumors is 1—5 %; of them, 0.43 % are bladder leiomyomas. The choice of treatment strategy primarily depends on the size and location of the tumor. Small endovesical leiomyomas can be removed by transurethral resection of the bladder, while in case of large (>5 cm) intramural or extravesical leiomyomas, laparoscopic resection is more effective. In this article, we report a case of large (>7 cm) bladder leiomyoma in a 28-year-old female patient. The patient has undergone laparoscopic resection of the bladder at P.A. Herzen Moscow Oncology Research Institute.

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

Prostate cancer is the actual problem of oncourology due to the steady increase in incidence. Despite active use of prostate cancer screening methods and introduction of new diagnostic markers into practice, the problem of overdiagnosis and over-treatment of this disease remains selevant. MicroRNAs are a promising biomarker, whose diagnostic and prognostic significance for prostate cancer is being actively studied now. This review provides information on microRNAs detected in the tissues of the prostate gland, blood and urine of patients with prostate cancer.

Prostate cancer is one of the most common urological malignancies. Improved diagnostic methods and widespread implementation of mandatory prostate specific antigen (PSA) testing in a number of clinics have led to an increase in the number of timely diagnosed cases of localized and locally advanced prostate cancer, as well as to the expansion of indications for radical therapies. Nevertheless, 30 % to 50 % of patients (depending on their risk) develop biochemical relapse after surgery or radiotherapy. Non-metastatic castration-resistant prostate cancer is usually a result of disease progression after radical treatment and long-term androgen-deprivation therapy, which manifests by constant increase in the PSA level along with castrate level of testosterone and no distant metastases according to the results of comprehensive radiological examination. A number of large clinical studies have demonstrated that regular examinations and control of PSA doubling time (main prognostic factor associated with poor disease outcome) are crucial to increase survival and prevent the development of distant metastases.This paper aims to provide an overview of existing literature on the problems associated with diagnosis and treatment of non-metastatic castration-resistant prostate cancer. We have analyzed large randomized studies that demonstrated an increase in the overall survival of patients receiving selective androgen receptor antagonists.

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.

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.

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.

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.

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 (

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.

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.