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Renal cell carcinoma is one of the most common malignant neoplasms of the genitourinary system. Along with smoking and hereditary syndromes associated with mutations in the Von Hippel-Lindau (VHL) gene, obesity is one of the main risk factors for the development of renal cell carcinoma. Emerging data indicate a causal relationship between obesity and development of renal cell carcinoma. In a large study within the framework of the Metabolic Syndrome and Cancer project, clinical data on blood pressure, body mass index, blood glucose, cholesterol and triglycerides were collected in 560,388 people. Individually, high glucose and triglyceride levels, as well as high body mass index and blood pressure, correlated with an increased risk of renal cell carcinoma in men, while only body mass index had a significant correlation in women.

Background. Renal cell carcinoma is one of the most common urologic cancers. Due to development of modern diagnostic methods, kidney tumors are often diagnosed at early stages (cT1a-T1b). The golden standard of treatment of localized renal cell carcinoma is tumor resection. In retroperitoneoscopic access, the time to artery access is decreased, the risk of intra- and postoperative complications is reduced. Retroperitoneal access is preferable for tumors located on the lateral or posterior kidney surface.

Aim. To analyze the results of treatment of patients after retroperitoneoscopic kidney resection.

Materials and methods. Between 2018 and 2021, at the A.F. Tsyb Medical Radiological Research Center - branch of the National Medical Research Radiological Center 47 retroperitoneoscopic kidney resections were performed (29 (61.7 %) in men, 18 (38.3 %) in women) due to stage cT1aN0M0 renal cell carcinoma. Retrospective analysis of demographic data, comorbid status, tumor characteristics, operative time, blood loss volume, frequency and severity of complications per the Clavien-Dindo classification was performed. Complexity of resection was evaluated using the R.E.N.A.L. scale.

Results. Mean patient age was 63 (38-79) years, body mass index was 29.9 (22-39) kg/m². Tumor of the left kidney was diagnosed in 24 (51.0 %) cases, of the right kidney - in 22 (46.8 %) cases, bilateral lesions - in 1 (2.2 %) case. Mean tumor size was 22.4 (11-39) mm. Resection had low complexity in 35 (74.5 %) cases, intermediate complexity in 12 (25.5 %) cases. Mean operative time was 156 (80-280) minutes, mean warm ischemia time was 19 (7-32) minutes, number of resections with zero ischemia was 15 (31.9 %), mean blood loss volume was 53 (10-300) mL, number of resections without renal parenchyma suturing was 10 (21.3 %). Mean hospitalization time after surgery was 5 days. Postoperative complications were observed in 4 (8.5 %) cases: bleeding (severity grade II per the Clavien-Dindo classification) in 1 (2.1 %) case, postoperative infectious complications (severity grade II) - in 2 (4.2 %) cases, subcutaneous hematoma (severity grade I) - in 1 (2.1 %) case.

Conclusion. Retroperitoneoscopic access is effective and safe. This is confirmed by low frequency and severity of postoperative complications. This access allows to reduce hospitalization time and pain management medication which accelerates patient mobilization and recovery. Comparative analysis shows that retroperitoneoscopic kidney resection has the same effectiveness as laparoscopic resection.

Background. Currently, organ-preserving surgery of kidney tumors often involves robot-assisted access. It can also be used in partial nephrectomy in patients with local recurrence after previous resection.

Aim. To evaluate the effectiveness of repeat robot-assisted partial nephrectomy of recurrent kidney tumors.

Materials and methods. At the Urology Center of the Mariinsky Hospital (Saint Petersburg) between 2018 and 2022 robot-assisted partial nephrectomy was performed in 86 patients (46 (59.5 %) men and 40 (40.5 %) women) with stage Т1а (n = 72) and Tib (n = 14) kidney tumors. Mean patient age was 58.0 ± 8.5 years, tumor size varied between 1.2 and 5.2 cm. Seven (7) patients were operated on due to tumor recurrence after previously performed partial nephrectomy. In all cases, lesion was located outside the site of primary resection. Mean time between the 1st and 2nd surgeries was 24 (12-46) months. Histological examination of primary tumor showed renal cell carcinoma in 4 patients, papillary carcinoma in 2 patients, chromophobe carcinoma in 1 patient. In 5 patients, one recurrent lesion was diagnosed, in 2 patients - two. Ligation of the renal artery was performed in 2 patients, its branch - in 3, ischemia-free resection - in 2 patients. Evaluation of mean operating time, blood loss volume, warm ischemia time, pre- and postoperative kidney function was performed.

Results. Mean operating time of repeat partial nephrectomy was 180 (130-210) minutes. Warm ischemia time for renal artery ligation was 16 and 20 minutes, for selective ischemia 14, 18 and 24 minutes. Mean blood loss volume was 220 (80-650) ml. No intraoperative complications were observed, grade I-II postoperative complications per the Clavien classification were observed in 2 patients. Mean decrease in glomerular filtration time was 8 % (from 62 to 54 mL/min/1.73 m²). During 16-month follow up period, tumor recurrence was not observed.

Conclusion. Robotic access allows to safely and effectively perform resection of recurrent kidney tumors with satisfactory functional and intermediate oncological outcomes.

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. Prostate cancer (PCa) is the 2nd most common oncological disease among men in the world. The first structured program of robot-assisted radical prostatectomy (RARP) was started in the year 2000. In the medical literature, a limited number of studies on long-term oncological treatment outcomes for patients with PCa after RARP is presented. In Russia, the Da Vinci robot was first installed in 2007. In the Urology Clinic of the A.I. Evdokimov Moscow State University of Medicine and Dentistry, the program of robot-assisted surgery was started in November of 2008.

Aim. To perform first in Russia evaluation of 10-year oncological treatment outcomes for patients with localized PCa after RARP. To perform comparative analysis with the outcomes of radical retropubic prostatectomy (RRP).

Materials and methods. Retrospective analysis of medical histories of 211 patients was performed. Among them, 62 patients did not satisfy the inclusion criteria. The remaining 149 patients were divided into 2 groups: 1^st - RARP (n = 82), 2^nd - RRP (n = 67). All RARP were performed by the same surgeon, RRP by 2 experienced surgeons.

Results. Median follow-up was 110.35 ± 24.58 and 115.19 ± 15.37 months in the 1^st and 2^nd group, respectively; median follow-up was 120 months in both groups (p >0.05). Survival was calculated using the Kaplan-Meyer approach. Ten-year biochemical recurrence (BCR)-free survival was 79.3 and 82.1 %, clinical recurrence-free survival was 96.3 and 97.1 %, metastasis-free survival was 92.7 and 94.0 %, cancer-specific survival was 93.9 and 95.6 % and overall survival was 85.4 and 86.6 % in the 1^st and 2^nd group, respectively. Mean time to BCR was 17.00 ± 20.67 and 22.83 ± 26.51 months, respectively ( p >0.05). Calculation of BCR predictors was performed using correlation analysis based on contingency test and Cramer's V-test. In the 1^st group, body mass index ≥30 kg/m² (p = 0.01), prostate-specific antigen level >10 ng/mL (p = 0.04), high progression risk per the D'Amico classification (p = 0.01) were independent preoperative predictors of BCR. Gleason score 7 (4 + 3) (p = 0.04) and ≥8 (p <0.0001) per pathomorphological examination, pT3 stage, extraprostatic extension, invasion into the seminal vesicles and positive surgical margin (all p <0.0001) were independent postoperative predictors of BCR.

Conclusion. RARP demonstrates long-term (10-year) oncological effectiveness comparable to oncological effectiveness of RRP in patients with localized PCa.

Background. Urine leakage from urethrovesical anastomosis (UVA) is a frequent and significant complication after prostatectomy.

Aim. To determine frequency urine leakage from the anastomosis after prostatectomy, evaluate diagnostic methods, develop classification and management guidelines for patients with this complication.

Materials and methods. A retrospective analysis of 1426 patients who underwent prostatectomy was performed. Results. In total, 97 (6.8 %) patients developed UVA failure in the early postoperative period. The complication was diagnosed on the 7th day after prostatectomy using retrograde cystography. An original classification urine leakage from the anastomosis after prostatectomy was proposed using numbers (0, I, II, III) and letters (A, B, C). In 50 (3.4 %) patients, grade I (A, B, C) UVA failure was diagnosed; 38 (2.7 %) patients had grade II (A, B, C) UVA failure; 9 (0.6 %) patients had grade III (A, B) UVA failure. The developed classification allows to accurately determine the severity of UVA failure and apply the appropriate methods for its correction.

Conclusion. Urine leakage from UVA is a serious problem in surgical treatment of prostate cancer. Currently, it is necessary to systematize the available data and introduce unified classification and algorithm for correcting this complication into clinical practice.

Background. Currently, the group of intermediate risk prostate cancer (PC) includes 2 subgroups - favorable and unfavorable intermediate risk according to the National Comprehensive Cancer Network (NCCN) classification. The optimal scope of therapy is not defined for the unfavorable intermediate risk subgroup. In particular, the need for and duration of hormone therapy (HT) during combined radiotherapy (CRT) have not yet been determined.

Aim. To perform a comparative analysis of the efficacy and toxicity of CRT in patients with unfavorable intermediate risk treated with and without HT.

Materials and methods. Eighty-four (84) patients with unfavorable intermediate risk PC were treated with CRT at the clinic of the A.F. Tsyb Medical Radiological Research Center between May 2016 and December 2020. Patients were divided into two groups: external beam radiation therapy + brachytherapy (n = 40) and external beam radiation therapy + brachytherapy + HT (n = 44). Conformal external beam radiation therapy was delivered with conventional fractionation to a total dose of 44-46 Gy and the ¹⁹²Ir high-dose rate brachytherapy was delivered with a single fraction of 15 Gy. Median duration of HT consisting of gonadotropin-releasing hormone agonist was 6 months. Median age was 65.2 years (range: 49-80 years). Median follow-up was 58.1 months (range: 18.6-83.7 months).

Results. With a median follow-up of 4.8 years, progression-free survival was 95 % and 97.6 % in the external beam radiation therapy + brachytherapy group and external beam radiation therapy + brachytherapy + HT group, respectively (p = 0.578). The break between treatment stages of more than 28 days was associated with a statistically significant increase in the risk of PC recurrence (p = 0.007). Overall survival for the external beam radiation therapy + brachytherapy group versus external beam radiation therapy + brachytherapy + HT group was 97.5 and 93.2 % (p = 0.376), respectively.

Late genitourinary toxicity was grade I in 8 (9.5 %) patients and grade II in 1 (1.2 %) patient. Urethral stricture developed in 3 (3.6 %) patients. Late gastrointestinal toxicity was grade I in 7 (8.3 %) patients and grade II in 1 (1.2 %) patient. There were no statistically significant differences in the incidence of late complications between groups with and without HT. There was a statistically significant (p = 0.049) effect of prostate volume on the incidence of late radiation proctitis.

Conclusion. There were no statistically significant differences in progression-free survival and overall survival in patients with unfavorable intermediate risk PC who received external beam radiation therapy + brachytherapy with or without HT. The incidence and severity of adverse events were acceptable and allowed patients with PC to maintain high quality of life.

Background. Metastatic castration-resistant prostate cancer remains a complex problem due to patients' previous treatments and limited selection of subsequent therapies. While 2^nd generation antiandrogens are initially effective, resistance to them is not an exceptional event. Mechanisms depending on androgen receptor and independent of it have been described. A special focus is on mutations in DNA repair genes, particularly genes involved in homologous recombination repair (HRR) as a possible cause of somatic genetic abnormalities specifically in progressive metastatic disease. However, data on the effect of the HRR defect on the effectiveness of antiandrogen therapy for prostate cancer are very limited, which requires additional clinical studies.

Aim. To evaluate the effect of clinical, morphological, molecular and genetic factors on the effectiveness of enzalutamide antiandrogen therapy in patients with prostate cancer and known mutations in DNA repair genes involved in HRR and mismatch repair.

Materials and methods. The study was performed at the Clinical Oncological Dispensary No. 1 (Krasnodar). Retrospective analysis of clinical and morphological parameters of 54 patients with prostate cancer who received enzalutamide antiandrogen therapy and with known status of germ line and somatic mutations of HRR DNA repair genes (BRCA1, BRCA2, ATM, BARD, BRIP1, CDK12, CHEK1, CHEK2, PALB2, RAD51B, RAD51C, RAD54L, FANCL) and microsatellite instability in immunohistochemical determination of mismatch repair deficit was performed. Statistical analysis was performed using IBM SPSS Statistics v.22 software.

Results and conclusion. In 17 of 54 patients, pathogenic germline and somatic mutations of HRR genes were detected: 7 mutations in BRCA2 gene, 4 - in CHEK2, 2 - in BRCA1, 2 - in CDK12, 1 - in BRIP1 and 1 - in ATM. It was shown that in the group of patients with metastatic castration-resistant prostate cancer, histological grade per the International Society of Urological Pathology (ISUP) G2 (total Gleason score 7 (3 + 4)) is significantly associated with the absence of HRR mutation, and grade G3 (total Gleason score 7 (4 + 3)) was associated with HRR mutations (р <0.05). Increase in prostate-specific antigen (PSA) level/biochemical progression 12-16 weeks after enzalutamide therapy start was significantly associated with metastatic castration-resistant prostate cancer without HRR mutations (р <0.05). In case of tumor response to enzalutamide therapy, decrease in PSA level did not depend on the age of disease onset, differentiation grade, primary advancement, previous docetaxel treatment, and presence of HRR mutation. Cox multivariate regression test showed that prescription of docetaxel before enzalutamide increased the risk of PSA-progression (hazard ratio (HR) 5.160; 95 % confidence interval (CI) 1.549-17.189; р = 0.008) and radiographic progression (HR 5.161; 95 % CI 1.550-17.187; р = 0.008). Progression risk decreased with increased level of PSA decrease 12-16 weeks after enzalutamide therapy start: for PSA decrease >30 % HR 0.150; 95 % CI 0.040-0.570; р = 0.005; for PSA decrease >50 % HR 0.039; 95 % CI 0.006-0.280; р = 0.001; for PSA decrease >90 % HR 0.116; 95 % CI 0.036-0.375; р = 0.000. Presence of HRR mutation, age <58 years, primary metastatic disease and poorly differentiated morphology did not affect duration without PSA-progression (p >0.05). Kaplan-Meier curves showed a trend towards increased time to development of castration resistance in the group of primary early cancer (Breslow р = 0.06; Tarone-Ware р = 0.062). Subgroup analysis showed that in the cohort of patients with castration-resistant prostate cancer (n = 48), absence of HRR mutation in patients who previously received docetaxel therapy increases time to PSA-progression compared to patients with mutations (log-rank р <0.05).

Background. Prostate cancer is one of the most common malignant neoplasms in the male population worldwide with high morbidity and mortality rates.

Aim. To study the main medial statistical indicators of prostate cancer in Saint Petersburg and other regions of the Russian Federation.

Materials and methods. The epidemiological indicators of prostate cancer for 2012-2021 in the Russian Federation, individual federal districts and Saint Petersburg were analyzed.

Results. The prevalence of malignant neoplasms of the prostate has increased in recent years. At the same time, the number of cases of early-stage disease diagnosis has increased, one-year mortality has decreased, and 5-year survival has increased, which indicates proper quality of oncological care for the population. In some federal districts, unstable or negative dynamics of indicators compared to the average Russian data are observed, which requires further analysis.

Conclusion. Evaluation of statistical measures of morbidity and mortality from malignant neoplasms of the prostate gland can be used to improve diagnostic algorithms and therapeutic tactics for this pathology.

Survival rates for cancer patients continue to steadily increase due to improvement of effectiveness of current treatments. However, despite significant oncological results, one should not forget about the quality of life of this cohort of patients, in particular those who undergo gonadotoxic cancer therapy with development of premature ovarian failure in women and azoospermia in men. Preservation of fertility in both women and men with cancer is currently possible and should be integrated at all levels of cancer care. In this regard, the main purpose of this review is to consider the topic of fertility in men treated for cancer in the context of various aspects of human life.

We present the largest testicular tumour that first ever reported in Malaysia and we believed first reported in Southeast Asia. A 21 years old Malay gentleman presented to us with painless large scrotal swelling. After the initial workup and investigations were done and followed by a CT scan which yield a multiple paraaortic lymph nodes, the patient was scheduled listed in the earliest list for high ligation right orchidectomy with an inguinal approach. The patient seeks treatment at that point because he can't bear the embarrassment and fear of the treatment.

Background. Ionizing radiation is an effective antitumor therapy, but it has a serious negative effect on the immune system requiring the use of radiation reaction prevention and reduction methods. Neutrophils are a sensitive element of the immune system both in interaction with tumor tissue and in response to radiation injury.

Aim. To evaluate functional activity of peripheral blood neutrophils by chemiluminescent analysis in patients with anorectal cancer after radiotherapy.

Materials and methods. The study included 80 patients with anorectal cancer. Patients received chemo- and radio-therapy with 3D conformal radiotherapy and radiation therapy under visual control, followed by the use of radioprotector and without it. Neutrophil activity determined by chemiluminescent analysis.

Results. In patients with anorectal cancer found maximum spontaneous and induced chemiluminescence acceleration. The chemiluminescence activation index with luminol is lower in patients with anorectal cancer, and with lucigenin shows no differences with the control group. The low luminol chemiluminescence maximum intensity, as well as the decrease in the synthesis of reactive secondary oxygen species in enzymatic systems, is likely regulatory intracellular limitations consequence. After treatment, patients with radioprotector showed a decrease in the number of parameters with statistically significant differences with the control group. Undesirable phenomena associated with sodium deoxyribonucleate therapy not detected in anorectal cancer patients during radiotherapy and subsequent observation period.

Conclusion. During treatment, differences in chemiluminescence parameters suggest that ionizing radiation affects them in patients with anorectal cancer receiving standard chemoradiotherapy. Use of chemoradiotherapy with a radioprotector leads to indirect restoration of cellular functional activity. This is confirmed by luminol-dependent chemiluminescence faster reaching its maximum and a decrease in the number of significant differences from the control group after the start of the drug treatment.

In the last ten years, the number of organ preservation surgeries for kidney cancer significantly increased. Per literature data, the incidence of recurrences after partial nephrectomy is between 2.9 and 11 %, mostly they are located in the operated or contralateral kidney. Positive surgical margin, high stage and histological subtype of the tumor, as well as hereditary diseases, can serve as predictors for recurrences. In renal cancer recurrences, radical nephrectomy, ablation therapy and repeat tumor resection are possible treatment methods. Kidney resection, same as in primary renal tumors, leads to chronic kidney disease and cardiovascular complications. Different ablation methods, despite their low invasiveness, are not always technically possible. Therefore, in patients with kidney cancer recurrence and satisfactory functional status, repeat partial nephrectomy can be a method of choice. The literature describes the outcomes of open repeat kidney resection with high incidence of general and severe complications. The number of these complications significantly decreased due to the use of robot-assisted access for resection of recurrent renal tumors. Functional characteristics of repeat kidney resections do not significantly decrease, especially in robot-assisted partial nephrectomy. Oncological outcomes of these surgeries remain intermediate, further prospective multi-center trials are needed for their confirmation.

Background. Bladder cancer, or urothelial carcinoma, is a common, aggressive, and still difficult to predict disease. For adequate therapy, timely diagnosis is essential since early detection of this tumor can significantly increase patient's survival at any age. Molecular genetic studies in cancer patients, including those with urothelial carcinoma, are becoming increasingly important. A number of major molecular genetic biomarkers of urothelial carcinoma are described in the world literature and used in clinical practice, however, information on the role of microRNA (miRNA) studies in the diagnosis of this disease has become available only in recent years.

Aim. To examine information of the world literature on the significance of miRNA identification in resected bladder tissues with non-muscle invasive urothelial tumors.

Materials and methods. We studied information from the world medical literature in the PubMed, CrossRef and Scopus databases dated between 2001 and 2022 on the significance of miRNA identification in resected bladder tissues with non-muscle invasive urothelial tumors.

Results. The results of the studies demonstrate that predictive levels of some miRNAs, as well as their associated proteins, should be assessed in the original tumor tissue and urinary vesicles in different clinical settings. The use of molecular genetic research, as one of the new diagnostic methods, will allow to personalize treatment for a particular patient and, if necessary, make a choice in favor of a more aggressive treatment method. In turn, this will increase the overall survival and quality of life of patients with aggressive tumors.

Conclusion. The next few years may bring many new discoveries that will help to unlock the secrets of miRNA dysregulation in urothelial carcinoma, leading to development and application of new targeted therapies in this patient population.

Background. In recent years, an increase in the incidence of multiple primary malignancies has been observed. Multiple primary malignancies are an independent occurrence and development of two or more neoplasms of different histological origin in one patient.

Aim. To evaluate epidemiological, clinical and morphological aspects of primary multiple malignant neoplasms of the prostate, kidney, and bladder.

Materials and methods. Data analysis of the work report of the Saratov region oncological service in 2019, presented by the Regional Clinical Oncological Dispensary, patient case histories in the archive of the medical information system was performed.

We performed a comparative analysis of the literature sources and data we obtained based to the following criteria: topographic anatomical combination of tumor locations, distribution of tumor combinations depending on time of occurrence (synchronous, metachronous), dynamics of urogenital multiple primary malignancies diagnosis in 2012-2019, distribution by gender and age, combination of stages of tumor process in both tumors, distribution by combination of histological types.

Results. Between 2012 and 2019, 783 cases of multiple primary tumors with lesions in the urogenital system were identified. We studied 186 cases with a combination of two malignant neoplasms in the prostate, kidney, and bladder. Tumors developed synchronously in 36 % of patients, metachronously in 64 %. Mean patient age was 75 years. Half of the cases were in the group of localized stages - 90 (48.4 %), with the most common combination of TI-TII stages observed in 46 (24.7 %) cases. Combinations of acinar adenocarcinoma of the prostate with urothelial carcinoma of the bladder (34.7 %), clear cell renal carcinoma (27.8 %), papillary urothelial carcinoma of the bladder (12.5 %) were the most common according to histological diagnosis of primary multiple tumors of the urogenital system.

Conclusion. Over the recent years we can observe a steady growth of diagnosable urogenital multiple primary malignancies. Morphological verification of the tumor and revelation of the most frequent histological types allows to assume the presence of the common mechanisms of development and the influence of tumor microenvironment on the growth of both tumors in a multiple primary malignancies pair.

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.