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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.

Objective: to analyze histological structure and identify predictors of detecting malignant non-seminoma in residual tumor masses obtained from patients with testicular non-seminomatous germ cell tumors (TNSGCTs) who had not achieved complete serological and radiological response to chemotherapy (CT).Materials and methods. This study included 96 out of 703 patients with TNSGCTs (13.7 %) operated on in N.N. Blokhin National Medical Research Center of Oncology. The inclusion criteria were as follows: verified advanced TNSGCT, elevated levels of alpha-fetoprotein and/or chorionic gonadotropin at the moment of CT initiation, at least 3 completed courses of first-line or second-line platinum-based CT, residual tumor foci after CT visualized with radiological methods, alpha-fetoprotein >7.29 IU/mL or chorionic gonadotropin >5 mIU/mL 3 weeks after the initiation of the last CT course, and surgery after CT. Histological examination of the primary tumors demonstrated that they contained elements of seminoma (n = 14; 14.6 %), teratoma (n = 29; 30.2 %), choriocarcinoma in (n = 23; 23.9 %), embryonal carcinoma (n = 45; 46.9 %), and yolk sac (n = 18; 18.8 %). All study participants received first-line CT; 58 of them (60.4 %) also received second-line CT. All patients underwent surgery after CT, including retroperitoneal lymph node dissection (RPLND) (n = 96; 100 %) and excision of extra-retroperitoneal lesions (n = 8; 8.3 %).Results. Histological examination of excised retroperitoneal masses showed that they contained areas of necrosis and fibrosis (n = 25; 26.0 %), teratoma (n = 29; 30.2 %), and viable malignant non-seminoma (n = 42; 43.8 %). There was a strong positive correlation between the existence of residual malignant non-seminomatous components in retroperitoneal masses and presence of choriocarcinoma (r = 0.300; р = 0.004), as well as the absence of embryonal carcinoma in the primary tumor (r = –0.300; р = 0.004), invasion of retroperitoneal metastases into major vessels and/or adjacent organs (r = 0.243; р = 0.017), and second-line CT prior to RPLND (r = 0.413; р Conclusion. Malignant non-seminomas were detected in 43.8 % of retroperitoneal and 62.5 % of extra-retroperitoneal residual tumorsremoved after CT in patients with advanced TNSGCTs and incomplete serological and radiological response. Discordant structure of metastases at different locations was observed in 50 % of patients. Our finding can be used to select candidates for surgical excision of residual tumors among these patients.

Objective: to describe the technique of nephrectomy and thrombectomy used in patients with renal cell carcinoma (RCC) and tumor venous thrombosis of various levels, and to identify risk factors of in-hospital death among operated patients.Materials and methods. This study included 768 patients with RCC and tumor venous thrombosis who have undergone surgical treatment. Median age was 58 years (range: 16-82 years); the male to female ratio was 2.3:1. The symptoms of venous tumor thrombosis were identified in 199 patients (25.9 %). In the majority of patients (n = 509; 66.3 %), the tumor thrombus originated from the right renal vein. The cranial border of the tumor thrombus was located in the perirenal inferior vena cava (IVC) in 219 patients (28.5 %), subhepatic IVC in 201 patients (26.2 %), intrahepatic IVC in 171 patients (22.3 %), and above the diaphragm in 177 patients (23.0 %). We used an individual approach to choose an optimal method of vascular control and to identify indications for circulatory support. Two-thirds of patients (n = 512; 66.7 %) underwent temporary block of the second renal vein; 268 patients (34.9 %) - temporary block of the hepatoduodenal ligament and right heart; 11 patients (3.2 %) were operated on with cardiopulmonary bypass.Results. The median surgery time was 190 ± 63.6 min; median blood loss was 3,000 ± 71.6 mL (≥50 % of circulating blood in 35.1 % of patients). Intraoperative complications were registered in 23 patients (3.0 %); eight patients (1.0 %) died during surgery with 4 of them died due to pulmonary embolism (0.5 %), 3 died due to hemorrhagic shock (0.4 %), and 1 died due to myocardial infarction (0.1 %). One hundred and ninety individuals (25.0 %) developed postoperative complications with Clavien-Dindo grade III-V complications observed in 115 cases (15.1 %). Forty-one patients (5.3 %) died in the early postoperative period. The causes of death included multiple organ dysfunction (n = 21; 2.8 %), pulmonary embolism (n = 7; 0.9 %), sepsis (n = 6; 0.8 %), stroke (n = 4; 0.5 %), myocardial infarction (n = 2; 0.2 %), and RCC progression (n = 1; 0.1 %). We have identified several independent risk factors for in-hospital mortality, including ascites (hazard ratio (HR) 8.3; 95 % confidence interval (CI) 3.2-21.4; p < 0.0001), preoperative pulmonary embolism (HR 3.5; 95 % CI 1.3-9.4; p = 0.013), supradiaphragmatic thrombi (HR 1.5; 95 % CI 1.1-2.0; p = 0.003). The in-hospital mortality rate was 3.5 % (20/575) among patients with no risk factors, 9.8 % (16/163) among those with 1 risk factor, 40.0 % (10/25) among those with 2 risk factors, and 60.0 % (3/5) among those with 3 risk factors (area under the curve (AUC) 0.705; p Conclusion. The incidence of severe complications and postoperative mortality rate in RCC patients with tumor venous thrombosis who have undergone nephrectomy and thrombectomy were 15.1 and 6.4 %, respectively. Risk factors for perioperative mortality included ascites, preoperative pulmonary embolism, and supradiaphragmatic thrombosis.

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.

This article analyzes first results of the randomized phase III clinical trial CheckMate 274 that has demonstrated the advantage of adjuvant immunotherapy with nivolumab, a PD-1 inhibitor, over placebo in high-risk patients with muscle-invasive urothelial carcinoma after radical surgery

Objective: to evaluate the outcomes of thrombectomy performed using different surgical techniques in renal cell carcinoma (RCC) patients with extensive tumor venous thrombosis.Materials and methods. This study included 345 RCC patients with extensive tumor venous thrombosis who underwent surgical treatment.The median age was 57 years (range: 16—79 years); the male-to-female ratio was 1:1.9. Two hundred and sixty patients (75.4 %) had their tumor thrombus originating from the right renal vein, 85 patients (24.6 %) — from the left renal vein. In 169 patients (49.0 %), the thrombus spread to the retrohepatic inferior vena cava (IVC), while in 176 patients (51.0 %), it spread above the diaphragm (to the intrapericardial IVC in 59 patients (17.1 %) and to the right heart cameras in 117 patients (33.9 %)). Regional metastases were found in 90 individuals (26.1 %), while distant metastases were observed in 124 patients (35.9 %). All patients underwent surgical treatment (radical in 251 patients (72.8 %) and cytoreductive — in 94patients (27.2 %)); the technique of vascular control and circulatory support was chosen individually. In 97 patients (28.1 %), the control over the cranial thrombus boarder did not require opening of the chest cavity; eleven patients (3.2 %) were operated on with cardiopulmonary bypass.Results. The median surgery time was 215 minutes; the median blood loss was 4500 mL. Intraoperative complications were registered in 209 patients (60.6 %) and postoperative complications were observed in 118 patients (35.1 %) (including those of grade I—II in 43 individuals (12.8 %) and grade III—V in 75 individual (22.3 %)). The in-hospital mortality rate was 10.7 % (37/345). At a median follow-up of 32.3 months, overall and diseasespecific survival rates among all patients were 51.9 % and 68.3 %, respectively; relapse-free survival rate in 226patients who have undergone radical surgeries and discharged from the hospital was 61.5 %; progression-free survival rate in 82 patients who have undergone cytoreductive surgery was 33.0 %. The method ofIVC control and circulatory support had no effect on both short-term and long-term treatment outcomes (p >0.05 for both).Conclusion. The use of minimally invasive techniques of vascular control and avoidance of cardiopulmonary bypass in carefully selected RCC patients with extensive tumor venous thrombosis do not worsen the outcomes of nephrectomy and thrombectomy.

The article is devoted to comparing the efficiency of algorithms for processing Bitcoin blockchain transaction database. The article describes the algorithm of vertex marking developed by the group. Based on the comparison of this and other algorithms, it is expected to identify the most effective algorithm for clustering addresses based on belonging to a single user. The Bitcoin database contains information about millions of financial transactions. Even though information about transactions is anonymous, there are methods for combining user addresses into wallets. In this article, we study algorithms of searching connectivity components, which are based on one of the methods of combining wallets based on the heuristic feature of the «total waste» of one user. The emphasis is placed on the practical aspects of implementation – hardware limitations in processing big data sets, as well as the choice of a solution for many graph connectivity components – the maximum connected set of graph vertices, in other words, a set of nonempty vertex sets and a set of vertex pairs.

The training module was developed by the staff of the department under the leadership of the head. Department of Academician of RAS, Professor I.V. Poddubnoy and Rector of FSBEI DPO RMANPO of the Ministry of Health of Russia, Corr. RAS, Professor D.A. Sychev.

Objective: to assess the expression and prognostic value of vascular endothelial growth factor A (VEGF-A), fibroblast growth factor 2 (FGF-2) and their receptors VEGFR-1, -2; FGFR-1, -2, as well as platelet-derived growth factor receptors (PDGFR-α, PDGFR-β) in paired samples of primary tumors and tumor thrombi in renal cell carcinoma (RCC).Materials and methods. Expression of VEGF-A, FGF-2, VEGFR-1, -2; FGFR-1, -2; PDGFR-α, -β was studied in paired surgical samples of primary tumors and tumor thrombi in 25 patients with clear cell RCC pT3a–T4N0–1M0–1 and tumor venous thrombosis by immunohistochemical assay using the appropriate Abcam/Santa Cruz Biotech antibodies from the immunohistochemical staining kit Invitrogen. Expression levels were evaluated by a semi-quantitative method (H-score). The analysis of the correlation between expression levels of VEGF-A, FGF-2, VEGFR-1, -2; FGFR-1, -2; PDGFR-α, -β and RCC characteristics, as well as evaluation of their influence on the outcome of RCC were performed.Results. VEGF-A, FGF-2, as well as VEGFR-1, -2; FGFR-1, -2; PDGFR-α, -β were expressed in the cytoplasm and on the membrane of the primary tumor and tumor thrombus cells in RCC patients. Tumor thrombus cells were characterized by lower expression of VEGFR-1, VEGFR-2, PDGFR-α (p ³2 identified risk factors was 27.3 %, risk factors – 87.5 % (p = 0.004).Conclusion. Tumor thrombus cells in RCC patients expressed VEGF-A, FGF-2, VEGFR-1, -2; FGFR-1, -2; PDGFR-α, -β less active than the cells of the primary tumor. Overexpression of growth factors and tyrosine kinases correlated with RCC Furman grade and tumor venous wall invasion. Overexpression of VEGFR-2 in both primary tumor and thrombus cells in combination with hypoexpression of VEGF-A in the thrombus negatively influenced on OS.

The World Health Organization has announced the coronavirus infection pandemic (COVID-19), associated with a high risk of severe complications requiring intensive care. The following is a possible algorithm for the choice of treatment tactics for prostate cancer during the COVID-19 pandemic, aimed at achieving 3 main goals: reducing the risk of life-threatening complications of the tumor process, minimizing the risk of “crossing” the profiles of adverse events associated with prostate cancer treatment and viral infection, and diminishing the risk of COVID-19 contamination for prostate cancer patients. The proposed algorithm is a personal view of the authors and is not an official recommendation.

Objective: to assess the results of organ-preserving treatment of patients with renal cell carcinoma (RCC).Materials and methods: 238 patients with renal tumors underwent partial nephrectomy at our institution between 1971 and 2006. 35(14.7%) of 238 patients were showed to have benign histology. RCC was revealed in 203(85.3%) cases on pathological examination. The latter group was retrospectively analyzed.Results: The indications for partial nephrectomy included bilateral lesions in 28.6%, solitary kidney in 3.9%, solitary functioning kidney in 1.5%, horseshoe kidney in 4.9%. An elective partial nephrectomy was performed in 61.1% of the patients. Local stage T was considered as T1 in 68.7%, T2 Р in 24.2%, T3а Р in 6.6%, T3в Р in 0.5% cases. Among 58 patients with bilateral lesions T stage of the contralateral kidney was considered as T1 in 25.9%, T2 Р in 10.3%, T3а Р in 12.0%, T3b Р in 3.5%, Tх Р in 48.3% cases. Positive lymph nodes (N+) were found in 2 (1.5%), distant metastases (M1) in 5 (2,5%) patients. An open partial nephrectomy was performed in 92.1%, laparoscopic in 2.5%, bench surgery in 4.4% cases. In 82.2% cases of bilateral RCC the surgery was performed on both kidneys. Five (2.5%) patients with solitary metastasis were treated with liver resection (1), pulmonary resection (1), scapular resection (1), contralateral adrenalectomy(2). Early surgical complications which required surgery occurred in 6.9% cases. Acute renal failure that necessitates dialysis was registered in 3.9%, chronic renal insufficiency with programmed dialysis in 1.0% of the patients. Renal artery clamping for more than 30 minutes significantly increased the risk of renal failure. Local recurrences appeared in 8.9% (local in 2.5%, distant in 6.4%) patients at a median of 56.1(3—120) months following surgery. The width of the surgical margin has no impact on local recurrence rate. 5-year cancer-specific and relapse-free survival of the whole group of patients was 93.4% and 82.5%, respectively; in the subgroups of uniand bilateral lesion, these were 95.1% and 89.6%, and 91.5% and 75.2%, respectively (p>0,05). T stage and presence of positive lymph nodes and distant metastases significantly influenced the survival.Conclusion: partial nephrectomy in patients with RCC has a low complication rate and provides an excellent long term survival in patients with localized disease.

Purpose of our study is to carry out: comparative analysis of results of radical prostatectomy and conformal radiotherapy in patients with clinically localized prostate cancer.Materials and methods. For retrospective analysis we chose data from 177 patients with stage сT1—2N0M0 prostate cancer treated in the N.N. Blokhin Russian Cancer Research Center of Russian Academy of Medical Sciences from 1997 to 2007. Median age of patients was 61,3 years and ranged from 38 to 76 years. Before treatment median level of serum prostate specific antigen was 15,5±15,1 ng/ml and median Gleason index — 2,6±0,7 + 3,2±0,6 = 5,7±1,1. Retropubic radical prostatectomy was performed in 133 (75,4%) patients and external conformal radiotherapy — in 44 (24,6%) patients. Study groups were matched according to main parameters. Median follow-up time was 26,2±30,2 months.Results. Prostate gland capsule invasion was found in у 43 (32,3%), perineural growth — in 56 (31,3%), invasion of seminal vesicles — in 12 (6,8%), angiolymphatic invasion — in 53 (29,9%), positive surgical margins — in 9 (5,1%), pN+ — in 7 (4,0%) from 133 operated patients. In all 44 cases compete responses to radiotherapy were registered. Among 177 patients 5-year survival was 95,0%, specific survival — 100%, and survival without PSA relapse — 76,8%. According to monofactorial and multifactorial analyses favorable prognostic factors for survival without PSA relapse are radical prostatectomy (р=0,003 and р=0,019 respectively) and Gleason index

Laparoscopic access allows radical nephrectomy and renal resection to be performed in patients with small tumors, including in those with renal cancer of T1-2, by providing the immediate and early results comparable with those of open interventions. The advantages of the laparoscopic access are low traumatism, less length of stay, a good cosmetic effect, and shorter rehabilitation. At the same time simultaneous operations may be performed. The future role of laparoscopy shall be defined when the 5-year survival rates are assessed.

Objective: to assess the results of treatment and to identify the predictors of survival in patients with transitional cell carcinoma of the urinary bladder with regional lymph node metastasis.Material and methods. A retrospective analysis of 56 patients with transitional cell carcinoma of the bladder (pT1—4aN1—2M0—1,) who underwent radical cystectomy at the N.N. Blokhin Russian Cancer Center between 1980 and 2005 was performed. Their median age was 58.6 years; males and females were 85.7 and 14.3%, respectively. Studer`s (19.7%), Bricker`s (73.2%) procedures and ureterocutaneostomy (7.1%) were used for urinary divertion. Thirty-six (64.3%) of the 56 patients received additional treatment: neoadjuvant chemotherapy (CT) (n = 2 (3.6%)), adjuvant therapy (n = 32 (57.1%)); CT (n = 24 (42.8%)), and radiotherapy (n = 6 (10.7%)), chemoradiation therapy (n = 2 (3.6%)), and neo- and adjuvant CT (n = 2 (3.6%)). The median follow-up was 21.7 months (1-97.6 months).Results. The effect of neoadjuvant CT was assessed as stabilization in all cases. Less than 15 lymph nodes were removed in 27 (48.2%), 15 lymph nodes or more were removed in 29 (51.8%) patients. The category pN+ was diagnosed in all cases: pN1 in 19 (33.9%), pN2 in 37 (66.1%). Involvement of nonregional (paraaortic) lymph nodes (pM+) was detected in 3 (5.4%) patients. Recurrences developed in 41 (71.9%) of the 56 patients on an average of 11.8 months after termination of treatment: localized regional and distant metastases in 3 (5.3%) and 35 (61.4%) patients, respectively; their combination in 3 (5.3%). In all 56 patients, overall, tumor-specific, and relapse-free 5-year survival was 32.1, 34.0, and 17.9%, respectively. Univariate analysis indicated that a history of superficial carcinoma (p = 0.036), as well as nonregional lymphogenic metastases (p = 0.036), and additional treatment (p = 0.020) were significant predictors. There was a trend for better survival in patients with pT < 3a (p = 0.056), after removal of more than 15 lymph nodes (p = 0.084), Bricker's operation (p = 0.055), and adjuvant therapy (p = 0.065).Conclusion. Multimodal approach for transitional cell carcinoma of the urinary bladder with regional metastases improves tumor-specific 5-year survival as compared with that after radical cystectomy alone.

Citochem is an effective and safe medication: main active substrate of the agent is gemcitabine. Citochem in combination with cisplatin provides satisfactory efficacy without high toxicity of treatment in patients with advanced transitional cell bladder cancer and can be recommended for use in clinical practice of oncourology.

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

Nephroblastoma (NB), a childhood embryonic tumor, accounts for less than 1% of all neoplasms in adults. The algorithm of an examination of patients aged above 14 years who has suspected NB should include angiography in addition to ultrasound computed tomography and computed tomography. Verification of its diagnosis in adults before therapy requires fine-needle tumor biopsy. Treatment for NB in adults should be multimodality and include neoadjuvant chemotherapy, primary tumor removal, and subsequent chemoradiation therapy. The prognosis is fair in patients over 14 years of age who had a localized NB and poor in those with locally extended and disseminated tumors. It is necessary to perform multicenter studies in order to develop an optimal therapeutic algorithm and to improve the results of treatment for NB in adults.

Objective. To compare the immediate and long-term results of laparoscopic and open radical nephrectomies in renal parenchymal tumors.Subjects and methods. The study covered 195 patients who underwent nephrectomy in 1986 to 2006. Their median age was 54,1 years; male/female ratio was 1,5:1. All the patients were divided into 2 groups. A study group comprised 102 (52,3%) patients with renal tumors, including 93 (91,2%) with renal-cell carcinoma (pT1-3N0-1M0-1) and 9 (8,8%) with benign tumors, who had undergone laparoscopic nephrectomy. Ninety-three (47,7%) patients who had undergone open radical nephrectomy for localized renal cancer were retrospectively selected for a control group. The median follow-up in the laparoscopic and open surgery groups were 19,6±13,2 and 62,3±35,9 months, respectively.Results. The median time of laparoscopic nephrectomy was significantly more than that of open surgery (170 and 100 min, respectively; p < 0,001). The median blood loss volume did not differ in the groups (280,1 and 283,5 ml, respectively; p = 0,342). In the study and control groups, the frequency of intraoperative complications was 10,9 and 4,3% (p = 0,075) and that of postoperative ones was 10,8 and 7,5%, respectively (p > 0,05). In 8 (7,9%) cases, conversion was required to suture defects of large vessels. In the laparoscopic group, the median length of stay was significantly less than that in the control group (7,0±3,6 and 12,0±3,1 days, respectively; p < 0,001). The differences were insignificant in the average cost of endoscopic and open surgeries. Questionnaire survey revealed a significant improvement in the quality of life after surgery via laparoscopic access. Relapses were detected in 2 (2,2%) patients from the study group: a local recurrence in 1 (1,1%) patient and metastases in 1 (1,1%); and in 5 (5,4%) control patients: metastases in 4 (4,3%), local relapse and distant metastases in 1 (1,1%; p = 0,271). In renal cancer patients undergoing laparoscopic and open nephrectomies, overall, specific, and relapse-free 4-year survival rates were 100; 100, and 94,9% and 96,4, 97,5, and 96,2%, respectively (p > 0,05).Conclusion. Laparoscopic nephrectomy is the method of choice in treating renal cancer — pT1—3aN0M0, which yields the same long-term results as open surgery and provides a better quality of life.

Purpose: to evaluate results of treatment of local recurrences of renal cell carcinoma (RCC). Material and methods: a retrospective analysis of 119 consecutive patients with local recurrence of RCC after nephrectomy treated from 1975 to 2007 at Cancer Research Center was performed. Mean age of the patients was 52.2 (19—75) years. A male to female ratio was 1.3:1. Local recurrences were localized in the renal fossa in 49 (41.2%), in retroperitoneal lymph nodes - in 46 (38.7%), in both renal fossa and retroperitoneal lymph nodes — in 24 (20.1%) cases. The tumor invaded neighboring organs in 59 (49.6%) of 119 patients. Metastases in the postoperative scar were diagnosed in 27 (22.7%), distant secondaries — in 38 (31.9%) cases. Surgery was performed in 78 (65.5%) cases (complete — 60 (76.9%), incomplete — 13 (16.7%), exploratory — 5 (6.4%)), 41 (34.5%) patients received conservative treatment. Neoadjuvant and/or adjuvant immunotherapy and/or chemotherapy were used in 14 (17.9%) of 78 patients treated with surgery. Of 41 (34.5%) patients receiving conservative treatment immunotherapy was administered in 25 (61.0%), chemotherapy — in 1 (2.4%), immunochemotherapy - in 11 (26.8%), hormonotherapy — in 4 (9.8%) (tamoxifen). Median follow-up was 23.3 (1—126) months. Results: Local recurrences were diagnosed a median of 33.0 (1-151) months after nephrectomy. Progression was registered in 33 (55.0%) of 60 patients following a complete removal of the relapse a median of 23.7 months after surgery (local — 10, distant metastases — 13, both local and distant metastases — 10). Four (12.1%) patients underwent repeat removal of the recurrent tumors, 29 (87.8%) received conservative treatment with no response. One-, 3- and 5 -year disease-specific survival of 119 patients was 72.6%, 41.4% and 30.5% respectively (median — 25.7±5.9 months). In the univariate analysis survival was affected by complete removal of the relapse (p=0.001), number of recurrent nodes (p=0.006), distant metastases (p=0.013) and presence of clinical symptoms (p=0.004). In the multivariate analysis the only factors affected survival significantly were radical surgery (p 0.005) and clinical symptoms of the relapse (p 0.024). Conclusion: Surgery is the only effective method of treatment in isolated recurrence of RCC following nephrectomy.

Carcinoma of the penis is a rare tumor. With adequate treatment of patients having no late metastases, 5-year survival is as high as 91.6%; 1-year relapse-free survival is 45.9%. Multivariance analysis shows that regional lymph nodal involvement is the only significant poor predictor in penile carcinoma, which reduces 5-year survival rates from 94.4 to 73.9%. Univariance analysis indicates that the partial effect of therapy, the endophytic form of primary tumor growth, a recurrence occurring after achievement of a complete therapeutic effect exert a significant negative action on survival. An insignificant survival reduction is observed in groups of patients less than 30 and more than 60 years with a neoplasm > 4 cm of high T stage being located on the glans et corpus penis.

Efficacy and safety issues of sorafenib (Nexavar) use in the treatment of patients with inoperable locally advanced and disseminated renal cell cancer are addressed. Several clinical studies of efficacy of treatment with sorafenib both in mono-regimen and combined with other drugs are discussed.

Objective: to compare the results of partial (PN) and radical nephrectomy (RN) in patients with renal parenchymal tumors with nephrometric PADUA index ≥8 and/or RENAL index ≥7 and functioning contralateral kidney.Materials and methods. Medical data of 114 consecutive patients with renal cell carcinoma (RCC) cT1–3aN0M0 and functioning contralateral kidney were included into the study: 57 (50.0 %) persons undergone PN for tumors with nephrometric PADUA index ≥8 and/or RENAL index ≥7 (the main group), and 57 (50.0 %) patients undergone RN (the control group). The groups were comparable with regards to demographic characteristics, nephrometric parameters, morphological tumor features, and baseline glomerular filtration rate (р >0.05 for all). Median follow-up – 52.0 ± 23.6 (9.1–138.5) months.Results. Technically complicated PNs were associated with an increase of median surgery time (by 39 min, р = 0.06), blood loss (by 319 ml, p within the groups. Chronic kidney disease (CKD) progression rate was significantly higher in RN than in PN group (40 % vs 31.6 % respectively, р = 0.050), including more frequent development of CKD stages III–IV (31.6 % vs 26.3 % respectively; р = 0.034). There was no difference of long-term survival between PN and RN groups, and that included survival results stratified according to gender, age, baseline CKD stage, PADUA and RENAL indexes. Five-year recurrence-free survival was 94.1 % vs 92.2 % (р = 0.223), cancer-specific survival – 92.3 % vs 90.8 % (р = 0.443), cardio-specific survival – 91.6 % vs 77.9 % (р = 0.549), overall survival – 89.8 % vs 70.7 % respectively (р = 0.858).Conclusion. PN is effective and safe method of treatment in patients with renal parenchymal tumors with PADUA index ≥8 and/or RENAL index ≥7 and functioning contralateral kidney, providing significant functional benefit without survival compromising when compared with RN.

Disseminated renal cell carcinoma is an immunogenic tumor in which cytokine immunotherapy is usually used as the second-line treatment. It is associated with a low frequency of objective responses and short progression-free survival. Modern studies resulted in more effective treatment regimens based on new high-affinity TKI multikinases (cabozantinib, lenvatinib), as well as immuno-oncological drugs that can specifically block intercellular transmission of anti-immunogenic signal (PD-1 inhibitors) (nivolumab, pembrolizumab) or its ligand type 1 (PD-L1) (avelumab), antigen type 4 associated with anticytotoxic T-lymphocyte (ipilimumab)). Cabozantinib is a 2nd generation multikinase inhibitor that blocks the receptors of growth factors MET, AXL, and VEGFR-2, which are involved in tumorigenesis and responsible for resistance to traditional antiangiogenic therapy in renal cell carcinoma. Registration studies have shown that cabozantinib together with combined targeted therapy is more effective in patients with favorable and intermediate prognosis, while the PD-1 inhibitor (nivolumab) – in patients with poor and intermediate prognosis.Objective:to analyze the results of cabozantinib studies and its possible use in the sequential treatment of disseminated renal cell carcinoma.

Objective: an assessment of efficacy and safety of lenvatinib in combination with everolimus in unselected patients with metastatic renal cell carcinoma (mRCC) progressed during or following ≥1 line of antiangiogenic targeted therapy.Material. Russian multicenter observational study ROSLERCM included 73 consecutive patients with morphologically verified mRCC progressed during or following ≥1 line of antiangiogenic targeted therapy, treated with lenvatinib (18 mg/d) and everolimus (5 mg/d) in 20 Russian centers. Median age of the patients was 59 (23–73) years, a male-to-female ratio – 3:1. Most common histological type of kidney cancer was clear-cell RCC (71 (95.8 %)). More than 2 lines of previous therapy were administered in 45 (61.6 %) cases. Most patients were diagnosed with multiple metastases (71 (97.3 %)) in >1 site (61 (83.6 %)). Nephrectomy was performed in 87.7 % (64/73) of cases. At the combined therapy start ECOG PS 2–4 was registered in 16 (20.5 %), poor prognosis according to IMDC score – in 33 (45.2 %) patients. Median follow-up was 9.7 (1–26) months.Results. Median progression-free survival achieved 16.9 (95 % confidence intervals (CI) 12.1–20.6), overall survival – 20.8 (95 % CI 15.7–25.9) months. Objective response rate was 11 % (8/73); tumor control was reached in 93.2 % (68/73) of cases. Median objective response duration was 10.5 (4.3–16.8) months, tumor control duration – 10.0 (2.5–17.5) months. Any adverse events developed in 83.6 % (61/73), adverse events grade III–V – in 23.3 % (17/73) of cases. Most frequent AE grade III–IV were diarrhea (10 (13.6 %)) and arterial hypertension (6 (8.2 %)). Unacceptable toxicity demanded treatment cancellation in 4.2 % (3/73), therapy interruption – in 30.1 % (22/73) and dose reduction – in 32.9 % (24/73) of patients.Conclusion. Unselected mRCC patients administered with combined targeted therapy in the real world practice were registered with similar survival, lower objective response rate, and better tolerability comparing with population assigned for lenvatinib plus everolimus in the randomized phase II trial.

Until now selection of the 1st line therapy for advanced clear-cell renal cell carcinoma was determined by patients distribution into favorable/ intermediate or poor prognosis groups. In the favorable/ intermediate prognostic groups agents of choice included antiangiogenic substances such as bevacizumab (in combination with interferon-alpha), sunitinib, andpazopanib, which had demonstrated only progression-free survival benefit comparing with interferon-alpha in registration studies; in the poor prognosis group the only treatment option was mammalian target of rapamycin inhibitor temsirolimus which had improved overall survival comparing with interferon-alpha. However about 75 % of advanced renal cell carcinoma patients have intermediate or poor prognosis. Only 2 randomized trials investigated systemic therapy in this cohort of patients, CABOSUN and CheckMate 214. The results of the randomized phase III study CheckMate 214 have demonstrated a significant advantage of overall survival and objective response rate in previously untreated patients of intermediate/poor prognostic groups who were randomizedfor combined immunotherapy with nivolumab and ipilimumab comparing with sunitinib independently of PD-L1 expression level. Owing to the achieved data combined immunotherapy became a new standard of the first-line therapy in advanced renal-cell carcinoma patients with intermediate and poor prognosis.

Objective : to assess safety of left renal vein (LRV) ligation during circular resection of the inferior vena cava in right-side kidney carcinoma with tumor venous thrombosis. Materials and methods . We selected medical data of 63 renal cell carcinoma patients with tumor venous invasion undergone nephrectomy, thrombectomy, IVC resection with LRV ligation (Group 1; n = 29 (46.0 %)) or preservation of venous outflow from the contralateral kidney (Group 2; n = 34 (54.0 %)). Median age of study participants was 56.0 + 8.8 years (range: 32—72 years); a male to female ratio was 1:1.9. Such parameters as age, gender, median glomerular filtration rate (GFR), stages of chronic kidney disease (CKD), blood loss, and duration of surgery were comparable across the two groups ( р >0.05 for all parameters). Median follow-up was 32.8 months (range: 1—226 months). Results. We observed no significant changes in median GFR in the late postoperative period compared to baseline among patients with ligated LRV (65.7 vs 71.2 mL/min/1.73 m2; р >0.05) and patients with preserved venous outflow from the contralateral kidney (60.6 vs 68.4 mL/min/1.73 m2; р >0.5). Patients that underwent LRV ligation were less likely to have reduced GFR compared to those with normal contralateral renal venous outflow (34.5 % vs 44.1 %; p >0.05). However, participants with ligated LRV had CKD upstaging (from stage 0—I to stage I—II) more frequently than participants with preserved venous outflow (27.6 % vs 5.9 %; р = 0.022). None of the patients developed stage III CKD after LRV ligation. Conclusion . LRV ligation during circular resection of the IVC in right-side renal cell carcinoma patients with tumor venous thrombosis does not lead to a clinically significant decrease in long-term deterioration of renal function.

The aim of the study is to assess the positive and negative prognostic factors of survival in patients with bilateral synchronous renal cancer (BRC). Materials and methods. The study was conducted on the basis of N.N.Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation. Cohort of patients with the synchronous BRC consisted of 160 patients between 1996 and 2014. All patients after finishing treatment were observed on an ambulatory basis during the period from 11 months to 12 years (median follow-up 81.05±46.7 months). We studied factors affecting 5-year survival rate, both positive and negative. Statistical analysis of the obtained results carried out using generally accepted statistical methods such as SPSS 23.0 - block of programs for Windows. Results. In case of synchronous BRC in 2/3 (65%) of patients the first kidney was operated on using organ-preserving surgery, in 1/4 of patients (n=21, 26.2%) both kidneys were operated on using organ-preserving surgery. In case of synchronous renal cancer the best results of survival, but without statistical significance (p=0.112) had patients with bilateral renal cancer who operated on using organ-preserving surgery. The 10-year overall survival in this group of patients was 90.5% in comparison with 62.5% - when nephrectomy was performed on the first stage and 76.4% in patients who had nephrectomy performed because of the renal cancer in the second kidney. Conclusions. The main factors affecting the 5-year survival rate of patients with synchronous BRC were: smoking, primary tumor size, age and type of surgery.

Objective: to assess advisability of nephrectomy, inferior vena cava (IVC) thrombectomy in renal cell carcinoma (RCC) with tumor venous thrombosis and pulmonary metastases. Materials and methods. We analyzed medical data of 112 consecutive RCC patients with tumor venous thrombosis and pulmonary metastases undergone nephrectomy, IVC thrombectomy at N.N. Blokhin Cancer Center from 1971 to 2014. Median age was 57 (19–77) years, a male-to-female ratio – 4.1:1. Tumor venous thrombosis occurred in all patients and achieved levels III–IV in 36 (32.1 %) cases. Ten (8.9 %) patients had solitary, 102 (91.1 %) – multiple lung metastases. Nephrectomy, thrombectomy was performed in all cases, 10 (8.9 %) patients also underwent complete resection of all pulmonary lesions. Eighty-eight (78.6 %) patients managed to receive systemic therapy. Median follow-up – 24 (3–148) months. Results. Median operative time was 185 (70–380) min, median blood loss – 4000 (200–18 000) ml. Intraoperative complications occurred in 25 (22.3 %), postoperative – in 37 (33.0 %) patients (Clavien–Dindo grade III–V – 27 (24.1 %)). Mortality rate was 9.8 %. Five-years overall and cancer-specific survival in all patients were 22.3 and 24.0 % respectively (median – 21.0 ± 3.6 and 21.0 ± 2.9 months respectively). Independent negative prognostic factors for cancer-specific survival were tumor pulmonary embolism before surgery (hazard ratio 269.4; 95 % confidence interval 112.4–314.6; р = 0.021) and contralateral renal vein tumor thrombosis (hazard ratio 83.1; 95 % confidence interval 78.2–178.3; р = 0.011). Conclusion. Nephrectomy, IVC thrombectomy is justified in selected RCC patients with tumor venous thrombosis and lung metastases without pulmonary embolism before surgery and contralateral renal vein tumor thrombosis. Nephrectomy, IVC thrombectomy is associated with acceptable complications rate and provides long-term survival comparable with the results of simple cytoreductive nephrectomies in historical series.

Objective: a preliminary assessment of safety, tolerability, and efficacy of lenvatinib in combination with everolimus in unselected patients with metastatic renal cell carcinoma (mRCC) resistant to antiangiogenic targeted therapy.Materials and methods. We analyzed medical data of 19 consecutive mRCC patients received lenvatinib in combination with everolimus following antiangiogenic targeted therapy failure. Median age was 55 (23–73) years. ECOG PS 0–1 was in 11 (57.9 %), ECOG 2–4 – in 8 (42.1 %) cases. Four (21.1 %) patients were distributed into the good, 10 (52.6 %) – into the intermediate, and 5 (26.3 %) – into the poor IMDC (International Metastatic Renal Cancer Database Consortium) prognostic group. Multiple metastases were diagnosed in 18 (94.7 %), multiple metastatic sites – in 17 (89.5 %), liver metastases – in 6 (37.6 %) cases. All the patients were previously treated with 1–4 lines of therapy (≥2 – 12 (63.1 %)). Median follow-up was 5 (2–10) months.Results. By the time of the analysis 12 (63.2 %) patients are being treated, 7 (36.8 %) – completed combined treatment (due to RCC progression – 4 (21.1 %), toxicity – 2 (10.5 %), death from unrelated reason – 1 (5.3 %)). Median time of completed therapy was not reached, mean treatment time was 5.1 (1.9–11.2) months. Adverse events were registered in 17 (89.5 %) patients (grade III – 3 (15.8 %), grade IV – 0, grade V – 1 (5.3 %)). The most common adverse events were diarrhea (68.4 %), stomatitis (57.9 %), hypertension (42.1 %), and weight loss (47.4 %). Lenvatinib or everolimus dose reduction was demanded in 5 (26.3 %) and 0, therapy interruption – in 5 (26.3 %) and 1 (5.3 %) patient respectively. Maximal response was assessed as partial in 1 (5.3 %) and stabilization – in 18 (94.7 %) cases. Decline of metastases size was registered in 12 (63.2 %) (median – 17 % (3–40 %)), stabilization – in 8 (42.1 %), enlargement – in 1 (5.3 %) patient. Median time to maximal response was 2 (2–4) months. Five-months overall and progression-free survival rates were 76.1 and 87.4 % respectively. Following 2 cycles of combined therapy ECOG PS improved in 11 (57.9 %), stabilized – in 6 (31.6 %), worsened – in 2 (10.5 %) patients.Conclusion. Our preliminary data have confirmed antitumor activity and showed acceptable tolerability of lenvatinib in combination with everolimus in unselected patients with mRCC resistant to antiangiogenic targeted therapy.

Immune-checkpoint inhibitors blocking the programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) and cytotoxic T-lymphocyteassociated protein 4 (CTLA-4) have shown a prominent anti-tumor activity with long-term responses and an acceptable toxicity profile in clinical trials. Pembrolizumab, atezolizumab, nivolumab, avelumab, and durvalumab are anti-PD-1/PD-L1 agents that redefine the standard of care for advanced urothelial carcinoma. CTLA-4 inhibitors are also under investigation in this setting. Phase III trial KEYNOTE-045 has demonstrated significant survival benefit in patients treated with pembrolizumab comparing with the standard second-line chemotherapy. Atezolizumab, nivolumab, avelumab, and durvalumab were also recommended for platinum-pretreated urothelial carcinoma patients based on phase II data. Following investigations of biomarkers such as PD-L1 expression are needed to determine high-responders to immunotherapy. This review article describes the advances in immunotherapy with immune-checkpoint inhibitors.

Objective: to assess the early and late functional results of partial nephrectomy in patients with solitary functioning kidney tumors.Materials and methods. Medical data of 131 consecutive patients with solitary kidney parenchymal tumor, who had undergone partial nephrectomy at the N. N. Blokhin Russian Cancer Research Center, were analyzed. The median age was 57 (26–75) years. All the patients were diagnosed with solitary kidney tumor (median RENAL score was 7.0 ± 2.4 and median PADUA score was 9.0 ± 2.2). The median baseline glomerular filtration rate (GFR) was 74 (33–159) ml/min/1.73 m2 (30 (22.9 %) – stage III chronic kidney disease (CKD) and 0 (0 %) – stages IV–V CKD). All the patients underwent partial nephrectomy (with ischemia in 98 (74.8 %) patients, including cold ischemia in 59 (45.1 %)). The median time of ischemia was 24 (7–80) min. The median blood loss was 800 (20–4500) ml.Results. Acute renal injury was recorded in 69 (52.7 %) cases; 6 patients (4.6 %) had indications for acute dialysis. The independent risk factors of acute renal injury were sinus invasion (hazard ratio (HR) 0.08; 95 % confidence interval (CI) 0.03–0.22; p = 0.051), baseline GFR 500-ml blood loss (HR 0.24; 95 % CI 0.12–0.51; p = 0.005). Progression of previously diagnosed CKD was recorded in 58 (44.6 %) patients; chronical dialysis was required in 2 (1.5 %) patients. The independent risk factors of CKD progression were sinus invasion (HR 0.38; 95 % CI 0.18–0.81; p = 0.002), medial location of the tumor (HR 0.19; 95 % CI 0.09–0.41; p = 0.001), baseline GFR, 500-ml blood loss and cold ischemia.

Objective. To evaluate short-term and long-term results of nephrectomy, thrombectomy, circular inferior vena cava (IVC) resection in patients with renal cell carcinoma (RCC) and advanced IVC tumor invasion. Materials and methods . Medical data of 49 patients with RCC and level II–IV tumor venous thrombus with advanced IVC wall tumor invasion were analyzed. All the patients underwent nephrectomy, thrombectomy, circular IVC resection (radical – 35 (71.0 %), cytoreductive, in M+ cases – 14 (28.6 %)). Circular resection of the infrarenal IVC segment was performed in 25 (51.0 %) patients; resection of the infrarenal, perirenal and retrohepatic IVC segments with a ligation of the left renal vein (RV) – in 24 (49.0 %) patients. Perirenal IVC prosthesis was used in 2 (4.1 %) patients with initially preserved IVC blood flow, in other cases replacement of the removed IVC segment wasn’t performed due to presence of a network of venous collaterals duplicating the IVC. Patients with metastases received systemic antitumor treatment after nephrectomy, thrombectomy. Results . Median operative time was 260 (135–580) minutes, median blood loss was 8750 (3000–27 000) ml. Severe intraoperative complications were observed in 2 (4.0 %) patients, 1 (2.0 %) patient died on the operating table due to hypovolemic shock. Postoperative complications were observed in 26 (53.2 %) cases (grade III–V in 22 (45.8 %) patients). Five-year overall and cancer-specific survival of all patients was 54.6 and 67.8 %, respectively, relapse-free survival of 35 patients with M0 category was 49.4 %. Both IVC prostheses were patent 12 months after the surgery. Function of the left kidney after ligation of the left RV was preserved at the preoperative level in all 24 patients in a median of 12 (2–120) months. Conclusion. Nephrectomy, segmental/subtotal cavectomy with preservation of the main renal venous entries is an effective treatment method in RCC patients with advanced tumor IVC invasion. The method allows to achieve satisfactory long-term survival rates and functional results.

Objective – to evaluate efficacy and safety of everolimus in Russian population of unselected patients with advanced renal cell carcinoma progressing after at least 1 line of anti-angiogenic targeted therapy. Materials and methods . In observational multicenter study CRAD001LRU03 from 17.01.2012 to 31.03.2015 in 43 centers 226 patients with advanced renal cell carcinoma with documented progression on the background or after at least 1 line of anti-angiogenic targeted therapy were included. The survey was conducted on all patients according to the practice, everolimus therapy was administered in accordance with instructions to the drug. Results. Objective response rate was 10 %, tumor control was achieved on 69.2 % of patients. Progression-free survival median – 7.8 months. Adverse events occurred in 44.7 % of patients, reached the III–IV severity of 9.3 %, were the reason for the cancellation of everolimus therapy in 2.2 % of cases. The most frequent complications of treatment were pneumonitis (n = 5 (2.2 %)) and anemia (n = 3 (1.3 %)). Conclusion. The observational study confirms efficacy and favorable safety profile of everolimus mTOR inhibitor in the Russian unselected patients with advanced renal cell carcinoma with progression or intolerable toxicity against background of anti-angiogenic therapy.

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

Objective: to assess the results of nephrectomy, thrombectomy in RCC patients with level III–IV tumor venous thrombosis with and without cardiopulmonary bypass.Materials and methods. Medical data of 167 consecutive RCC patients with level III–IV tumor venous thrombosis underwent nephrectomy thrombectomy in N.N. Blokhin Russian Cancer Research Center between 1998 and 2012 were collected. Right side tumor was in 122 (73.1 %), left side – in 42 (25.1 %), bilateral – in 3 (1.8 %) cases. The extent of thrombus was defined as intrahepatic in 82 (49.1 %), supradiaphragmatic – in 85 (50.9 %) (intrapericardial – in 44 (26.3 %), intraatrial – in 39 (23.4 %), intraventricular – in 2 (1.2 %)) cases. Nephrectomy, thrombectomy with cardiopulmonary bypass was used in 9 (5.4 %), 158 (94.6 %) patients underwent radical nephrectomy with thrombectomy without CPBP and sternotomy. Intrapericardial IVC and right atrium were exposed through transdiaphragmatic approach and providing vascular control over infradiaphragmatic IVC and renal veins.Results. Median blood loss was 6000 (600–27 000) ml. Complications rate was 62.8 %, 90-day mortality – 13.2 %. Intraoperative complications were registered in 80 (47.9 %), postoperative – in 66 (40.5 %) (grade II – 16 (9.8 %), grade IIIb – 1 (0.6 %), grade IVа – 28 (17.2 %), grade IVb – 3 (1.8 %), grade V – 18 (11.1 %)) patients. Modified thrombectomy technique insignificantly decreased blood loss compared to thrombectomy with CPB, did nоt increase complications rate including pulmonary vein thromboembolism, or mortality. Five-year overall, cancer-specific and recurrence-free survival was 46.2, 58.3 and 47.1 %, respectively. Thrombectomy technique did nоt affect survival.Conclusion. In selected patients with mobile thrombi transdiaphragmatic approach allows to avoid the use of CPBP and decrease surgical morbidity without survival compromising.