Introduction. Clear cell renal cell carcinoma (ccRCC) is characterized by the high (30–40 % of cases) frequency of lethal outcomes which at metastasis reaches 90 %. Lack of efficient diagnostics at early stages of a disease indicates the need of searching on new ccRCC markers.

Objective: for definition of methylation role of some tumor suppressor microRNA (miRNA) genes in ccRCC pathogenesis and progression and marker identification for ccRCC diagnostics and metastasis predictions.

Materials and methods. The alterations of methylation status of 10 miRNA genes were determined by methylation specific polymerase chain reaction in tumor DNA samples and matched histologically unchanged tissues from 70 patients with ccRCC, as well as in DNA samples of kidney tissues from 19 post-mortal individuals without cancer history. Methylation of MIR MIR-107, -130b and -148a genes in ccRCC was studied for the first time.

Results. It was shown that 8 miRNA genes (MIR-9-1/3, -34b/c, -124a-1/2/3, -129-2, -130b) were methylated in ccRCC tumors with significantly higher frequency than in the matched histologically unchanged kidney tissues. It was established the association of methylation of 4 miRNA genes (MIR-107, -124a-3, -129-2, -130b) with ccRCC progression (stage, tumor size, differentiation grade), including metastasis in the lymph nodes or distant organs, revealed for MIR-107 and -129-2. The association of MIR-107 and -130b methylation with progression of ccRCC is shown for the first time. Potential marker systems are made for ccRCC diagnostics using tumor biopsy; according to the ROC analysis, systems from 4 and 5 genes (MIR-9-1, -4b/c, -124a-3, -129-2/with addition of MIR-130b) are characterized by high clinical sensitivity of 90 % and specificity of 94 % (area under ROC curve 0.93 and 0.94). 

Conclusion. The received results will form the basis of noninvasive ccRCC diagnostics further development. To conclude, it is shown the association of methylation of 9 miRNA genes with ccRCC pathogenesis and progression and its potential diagnostic value.

Introduction. Multilocular cystic renal cell neoplasm of low malignant potential (MCRCNLMP) or multilocular cystic renal cell carcinoma (MCRCC) is classified as a distinct nosological unit. Currently, in literature there are no results of studies based on a large number of observations.

Objectives: to systemize clinical and pathomorphological characteristics of MCRCNLMP.

Materials and methods. In the period from January 2011 to December 2015 in the clinic of the N.N. Lopatkin Scientific Research Institute of Urology and Interventional Radiology, 32 cases of MCRCNLMP were diagnosed among 588 patients. We have studied clinical and morphological characteristics of this disease, surgical approaches to its treatment, and long-term results, which we present in this article.

Results. MCRCNLMP comprised 5.44 % of all histological cases of RCC. The majority (75 %) of patients didn’t have clinical manifestations of the disease. Т1а tumor stage corresponded to 65.6 % of tumors, Т1b stage to 28.1 %, and Т2 stage only to 6.2 %. In all cases neoplasm was characterized by moderate and mild differentiation (G1–2) per the grading system of the International Society of Urological Pathology (ISUP). Only 25 % of patients had normal body mass index. In 31 of 32 patients, long-term outcomes were observed. Median follow-up duration was 29 (14–66) months. Progression of the disease wasn’t observed in any of the patients.

Conclusion. Patients with MCRCNLMP have the best oncological prognosis among patients with RCC. The necessity of classification of this tumor in accordance with the TNM system is currently dubious. Only organ-preserving surgeries should be used in treatment of the disease. For cases of MCRCNLMP, it is recommended to increase periods of control examinations proposed for patients with RCC, and diagnostic manipulations should be minimal.

Introduction. Renal cancer is one of the leading urological cancers due to annually increasing morbidity and mortality rates.

Objective: to prove the efficiency of preventive hemostatic sutures during partial nephrectomy for maximal preservation of functional renal parenchyma in patients with renal cell carcinoma.

Materials and methods. We developed and implemented a new technique of partial nephrectomy with preventive hemostatic suture, that allows not to clamp the renal pedicle, even in case of central tumor location. Main benefit of this technique is minimization of kidney function loss after the operation, which is the major aim of nephron sparing surgery. Study included 150 patients with pT1a–pT2bN0M0 kidney cancers. Central tumor location was in 64 patients, 45 patients had upper segment tumors and 41 lower segment tumors. 74 patients had T1a tumor stage, T1b and T2a stage observed in 53 and 4 patients respectively. Nineteen patients were diagnosed with cystic carcinoma. To evaluate renal function, dynamic nephroscintigraphy was carried out and volume indices were calculated by computed tomography data.

Results. All patients underwent nephron sparing surgery using preventive hemostatic sutures. Mean operative time was 180 ± 40 minutes, mean anesthesia time was 190.5 ± 15.0 minutes. Mean blood loss was 250 ± 70 ml. We didn’t used arteria clamping and warm ischemia and there was no conversions to nephrectomy during all partial nephrectomies. Perfusion index of the kidney before the surgery was 54.13 ± 2.00 %, after the surgery 46.23 ± 3.00 %, renal index was 53.24 ± 4.00 % and 46.82 ± 2.39 %, respectfully. In our opinion decreasing of renal indexes in early postoperative period is associated with loss of kidney parenchyma due to the surgery. Mean kidney volume was 140 ± 30 cm3 with 120 ± 20 см3 functional parenchyma volume and mean tumor volume 40 ± 20 сm3. Functional parenchyma volume after surgery insignificantly decreased to 115 ± 20 сm3.

Conclusion. Preventive hemostatic sutures during partial nephrectomy allows to remove the tumor in almost any part of the kidney. Rejection of renal hilum clamping minimizes ischemical damages of renal parenchyma.

 

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 <80 ml/min/1.73 m2 (HR 0.45; 95 % CI 0.22–0.92; p = 0.021), parenchymal ischemia (HR 0.13; 95 % CI 0.05–0.33; p = 0.032), and >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, <60 ml/min/1.73 m2 (HR 0.24; 95 % CI 0.10–0.56; p <0.0001), warm ischemia (HR 0.41; 95 % CI 0.17–1.00; p = 0.052).

Conclusion. Solitary kidney resection is associated with a low risk for renal function loss. To achieve optimal functional results, it is desirable to follow the balance between the indications for renal vessel ligation and the need to avoid >500-ml blood loss and cold ischemia.

Introduction. Surgery remains the main method of treatment of patients with bladder cancer, and the only radical surgery is cystectomy with lymphadenectomy and a rationally selected method of urinary diversion. In the Chelyabinsk Regional Clinical Oncological Dispensary, an original method of orthotopic neobladder reconstruction in bladder cancer patients was developed.

Objective: to improve the results of surgical treatment and the quality of life of patients with bladder cancer who underwent cystectomy.

Materials and methods. The article presents results of a study of patients with bladder cancer who underwent orthotopic ileocystoplasty after radical cystectomy using a unique original technique. The reservoir was formed using a segment of the ileum of 45–50 cm in length with a 20–25 cm offset from the ileocecal junction. It’s important to preserve nutrition of the resected fragment. One of the branches of the ileocolic artery supplies blood to the distant part of the ileum which explains the necessity of the offset. After examination of the mesentery for unusual blood supply, the necessary intestinal segment was resected. Intestinal patency was restored by application of an anastomosis side-to-side with double row suture on the mucosa and serous-muscular layer. The reservoir was formed by application of an enteroenterostomy side-to-side with one row inverting continuous suture. Before that, the resected small-intestinal segment was detubulized (dissected) through the antimesenteric margin for 12–15 cm.

Results. This method has the lowest rate of complications; doesn»t affect overall, cancer-specific and recurrence-free survival.

Conclusion. The proposed method of neobladder formation allows to significantly improve the results of bladder cancer treatment.

Objective: to identify the most important factors influencing the development of complications after radical cystectomy (RCE).

Materials and methods. The results of 182 RCEs performed in September 2014 and December 2016 were analyzed. The patients included 152 (83.5 %) men and 30 (16.5 %) women. The patients’ age ranged from 31 to 84 years (mean age 62.3 years). An orthotopic urinary reservoir was formed in 138 (75.8 %) patients. Postoperative complications were evaluated according to the Clavien–Dindo classification. The calculations were made with a computer program for SPSS Statistics 16.

Results. No complications were recorded in 84 (46.2 %) patients within 30 days after RCE. The development of various postoperative adverse reactions was observed in 98 (53.8 %) patients. The most common complications were gastrointestinal (26.9 %) and infectious (25.8 %). Sixteen (8.8 %) patients developed grade I complications; grades II, III, IV, and V complications were seen in 53 (29.1 %), 21 (11.5 %), 5 (2.7 %), in 3 patients, respectively. Thirty-day mortality was 1.64 %. Univariate regression analysis has established that overweight (p = 0.031), T status (p = 0.021), preoperative hemoglobin levels (p = 0.001), intraoperative blood loss (p = 0.009), and intraoperative abdominal cavity infection (p <0.001) play a significant role in the development of complications following RCE. Multivariate regression analysis has revealed that the frequency of complications after RCE is influenced by body mass index (p = 0.008), preoperative anemia (p = 0.034), blood loss (p = 0.003), and intraoperative abdominal cavity infection (p <0.001).

Conclusion. RCE is often accompanied by the development of different categories and severity of complications. Identification of risk factors for their complications will be able to elaborate effective ways for their prevention.

Introduction. One of the problems of urologic oncology is that patients with bladder cancer (BC) show up late for appointments, which leads to increased numbers of patients with advanced cancer stages accompanied by symptoms considerably reducing their quality of life. In most similar cases, external beam radiation therapy (EBRT) may be given with palliative intent to lessen or relieve the local symptoms of disease and to deliver the highest possible dose of radiation to bladder tumor.

Objective: to assess the efficacy and toxicity of palliative EBRT in patients with BC.

Materials and methods. Outcomes of palliative EBRT that had been given to 103 patients with BC were analyzed. Poor somatic health status of these patients caused by underlying disease or accompanying pathology made radical treatment impossible.

Results. During EBRT treatment, hematuria was stopped in 56 (72.7 %) and reduced in 21 (27.3 %) patients. After completing EBRT, bladder pain syndrome was relieved in 13 (76.5 %) of 17 patients, but in 1 patient the pain got worse, and in 3 (17.6 %) patients no changes in this symptom occurred. Acute bladder reactions were observed in 37 (35.9 %) patients: grade I–II (RTOG) in 32 (31.1 %) patients and grade III–IV in 5 (4.8 %) patients. Acute grade I–II rectitis was noted in 10 (9.7 %) patients. Late grade I–II bladder complications (RTOG/EORTC) occurred in 16 (15.5 %) patients, and late rectal complications in 2 (1.9 %) patients. Due to relief of local symptoms and improvement of somatic health status in 16 (15.5 %) patients, it was possible to perform radical treatment for BC. At 12 months after treatment, objective tumor response was achieved in 34 (33.0 %) and stable disease in 14 (13.6 %) BC patients.

Conclusion. Radiation therapy is an effective method of palliative care of patients with advanced BC and marked local symptoms. In most cases, EBRT can help stop or reduce hematuria and pain as well as improve quality of patient life. Therefore, it is necessary to develop methods of effective palliative care for patients with complicated advanced BC. A personalized approach to optimize programs palliative treatment of BC is a promising direction for further research.

Objective: to assess safety, responses rate and duration, progression-free and overall survival in patients with advanced urothelial carcinoma receiving vinflunine as second-line therapy in routine clinical practice, after additional patient recruitment.

Materials and methods. This retrospective observational multicenter study included medical data of 34 patients with verified advanced urothelial carcinoma receiving vinflunine for tumor progression after first-line chemotherapy in 11 Russian clinical centers from March 23, 2013 to June 3, 2017. The median age of the patients was 60 (44–81) years. ECOG performance status was 0 in 2 (5.9 %), ECOG 1 – in 21 (61.7 %), ECOG 2 – in 9 (26.5 %), and ECOG 3 – in 2 (5.9 %) patients. Visceral metastases were present in 14 (41.2 %), non-visceral – in 20 (58.8 %) cases. Anemia was recorded in 20 (58.8 %) patients. According to Bellmunt scale 2 (5.9 %) patients had none risk factors, 6 (17.6 %) had 1 risk factor, 18 (52.9 %) and 8 (23.5 %) had 2 and 3 risk factors, respectively. Initial vinflunine dosage was 320 mg/m2 in 6 (17.6 %) patients, 280 mg/m2 in 22 (64.8 %) or 250 mg/m2 in 6 (17.6 %). Patient received a median of 4 (1–10) cycles of therapy.

Results. Adverse events (AE) were recorded in 33 (97.1 %) cases. The most frequent were general (70.6 %), hematologic (58.8 %), and gastrointestinal AE (41.1 %). Most AE were grades I–II and well-controlled. There were no deaths caused by adverse events. The best response was assessed as complete in 1 (2.9 %), partial – in 5 (14.7 %), stabilization – in 19 (55.9 %), and progression – in 9 (26.5 %) of the 34 patients. Complete response duration was 9.0 months, median partial response duration was 8.0 months (95 % confidence interval (CI) 5.5–13.0); median stabilization duration – 3.5 months (95 % CI 0.7–12.8). Median progression-free and overall survival were 3.9 (95 % CI 3.5‒4.3) and 6.4 (95 % CI 0.1–17.0) months, respectively. Univariate analysis indicated that the low somatic ECOG status and the initial vinflunine dosage of 250 mg/m2 had adverse impact on overall survival.

Conclusion. The efficacy and safety of vinflunine as second-line therapy for first-line chemotherapy-resistant advanced urothelial carcinoma in unselected patients are similar to the results of Phase III randomized trial and early results of the Russian observational study.

Introduction. Prostate cancer (PCa) is one of the common oncological diseases in men. Expression of the PCA3 gene in urine is currently used as a molecular genetic marker of PCa.

Objective: to comparative analysis of the PCA3 expression in urine sediments and exosomes for the determination of the biomaterial, which allows detecting the PCA3 expression in more efficient manner.

Materials and methods. The 12 patients with different stages of PCa and 8 control samples were examined.

Results. The diagnostic accuracy of the PCA3 gene expression analysis in this cohort exceeded 90 %. We had not obtained significant differences in the sensitivity and specificity of the PCA3 hyperexpression in the urine sediments compared with exosomes. This result indicates in favor to using urine sediment for the PCA3 analysis as a biomaterial with less time-consuming sample preparation, although the possible advantage of exosomes for the analysis of the expression marker panels requires further studies.

Introduction. Standard prostate biopsy with subsequent histological verification is now an integral part of the diagnosis of prostate cancer (PC); however, the number of false-negative results and cases of underestimation of the degree of tumor aggressiveness remain excessively high. The active and massive clinical introduction of multiparametric magnetic resonance imaging (mpMRI) in combination with hybrid technologies, such as MRI/ultrasound fusion biopsy, can significantly increase the detection rate of moderate- and high-risk cancers.

Materials and methods. This investigation covered 33 patients with suspected PC that was detected in 69.7 % of the patients.

Results. The comparative histological results from targeted and standard prostate biopsies showed the detection rate of clinically significant cancer (a total Gleason score of ≥7), which was equal to 86.7 and 66.7 %, respectively. The results of targeted biopsy were statistically significantly (correlation coefficient r = 0.8; p <0.0001) similar to those of standard biopsy in terms of the degree of identifying nodules with the highest malignancy potential; at the same time a regression analysis revealed that the accuracy of high-risk cancer detection in the target biopsy was higher than that of standard biopsy (p <0.0001). Thus, MRI/ultrasound fusion-targeted biopsy demonstrated a lower sensitivity in detecting clinically insignificant PC than standard biopsy. Data of mpMRT with grading in accordance with the Prostate Imaging Reporting and Data System (PI-RADSv2) showed a statistically significant correlation with the results of the targeted biopsy (correlation coefficient r = 0.7; p <0.02). 

Conclusion. The further vector of development of prostate biopsy will most likely be reduced to the concept of targeted, or “sighted”, biopsy, which in turn can significantly increase the detection rate of clinically significant forms of PC, rightly define the clinical stage of the disease, and correctly stratify risks.

Objective – disclosure of the main advantages of prostate biopsy under the magnetic resonance imaging (MRI) control, consideration of technical aspects of its implementation.

Materials and methods. Advances in multiparametric MRI have lead to improved detection of prostate tumors. The fusion of MRI data with transrectal ultrasound enables the targeted biopsy of suspicious areas. The results of fusion-biopsy were analyzed in 38 patients. The mean age of patients was 61.3 (44–70) years. All the patients underwent at least 1 transrectal prostate biopsies. The average number of biopsy cores was 24.3 (17–30), the average value of total prostate-specific antigen before saturation biopsy was 10,4 (0.20 to 34.16) ng/ml.

Results. Prostate cancer was diagnosed in 52.7 % of cases (20/38). Better prostate cancer detectability during repeated saturation biopsy generally occurred due to the localized forms of the disease (93.3 %).

Conclusion. Fusion biopsy allows prediction of a pathological stage of prostate cancer, Gleason grade of a tumor and its site localization with a greaterprobability. Most tumors detectable by saturation biopsy were clinically significant, which makes it possible to recommend fusion biopsy to some cohort of high prostate cancer risk patients.

Introduction. Enzalutamide and abiraterone are used for treatment of metastatic castration resistant prostate cancer (mCRPC). Both drugs were proved to be effective in randomized control trials.

Objective. This pharmacoeconomic evaluation compared enzalutamide and abiraterone used prior to chemotherapy in patients with mCRPC from the Russian healthcare system perspective.

Materials and methods. Based on clinical trials results we proposed an mCRPC Markov chain stochastic process model and calculated medical costs per 1 mCRPC patient. We also conducted cost – effectiveness, cost – utility and budget impact analysis.

Results. Monthly medication costs for enzalutamide was 29 478 rubles (11.7 %) less than for abiraterone + prednisolone. The 4 year total medical costs for enzalutamide was 318 thousand rubles (5.0 %) less than for abiraterone + prednisolone. Enzalutamide was also found to be cost – effective compared to abiraterone.

Conclusions. Enzalutamide is a rational option for mCRPC treatment.

Objective: to investigate whether it is expedient to use the selective vasopressinergic V1 receptor agonist Remestyp® (terlipressin) to reduce the amount of blood loss and the duration of urologic cancer surgery.

Materials and methods. Remestyp® was used as a selective vasopressor. The fact that the drugs in this group can be used in cancer surgery is due to their ability to induce pronounced vasospasm of the microvasculature of the parenchymal organs, by considerably reducing blood flow in the latter, which, by taking into account the abundant vascularization of tumor tissue with numerous arteriovenous anastomoses, allows more optimal surgical conditions to be created. At the same time, it should be noted that selective vasopressors do not enhance blood cell aggregation, which is especially important for urologic cancer patients who are often at an increased thrombosis risk due to the presence of comorbidity, advanced age and surgical duration. The retrospective and prospective studies enrolled 54 patients operated on for urologic cancer in the period from 2014 to 2015.

Results. Analysis of the results of the studies showed that the use of the drug from the group of vasopressinergic V1 receptor agonists resulted in decreased intraoperative blood loss in patients and contributed to a shorter surgical treatment duration.

Conclusion. The findings suggest that it is expedient to use selective vasopressors for surgical treatment quality improvement in urologic oncology.

Prostate cancer morbidity and mortality rates are steadily increasing in Russia and the world. The etiology of this cancer has not been adequately studied. In particular, the role of high-risk human papillomavirus types that are potent biological carcinogens in a number of other human organs remains unclear. Different laboratories worldwide continue to provide information, the authors of which make mutually exclusive conclusions regarding the involvement of these viruses in the genesis of prostate cancer. This review contains an analysis of the data available in the literature on the possible involvement of human papillomaviruses in prostate cancer.

Optimization of treatment of metastatic renal cell carcinoma (mRCC) is an important problem of modern oncological urology. Targeted drugs replaced immunotherapy with cytokines and became the new standard of treatment. Their introduction resulted in increased patients» lifespan and fundamentally changed treatment of kidney cancer. Since 2005, 9 targeted drugs and 1 combination of lenvatinib and everolimus were registered and approved for treatment of mRCC. All of these drugs, except cabozantinib, are available in Russia. Currently, in mRCC treatment subsequent prescription of the drugs is used, i. e. patients receive several lines of targeted therapy. We still can»t name the most effective sequence of the 1st and 2nd lines of mRCC therapy due to a lack of clear algorithms of drug prescription. Currently, axitinib, cabozantinib,  everolimus, nivolumab, and sorafenib (in alphabetic order) and the combination of lenvatinib and everolimus are recommended for the 2nd line of mRCC therapy. However, there weren’t any direct comparative studies of their effectiveness, and therefore knowledge about differences between the targeted agents can make the selection more straightforward.

More than 90 % of patients with metastatic castration-resistant prostate cancer (CRPC) have radiologically confirmed skeletal metastases. Traditional treatment methods such as administration of painkillers, external beam therapy, bisphosphonates or denosumab, as well as injections of strontium-89 or samarium-153 radionuclides, have only palliative effect and in some cases can postpone development of skeletal complications. Alpha-emitter radium-223 dichloride (Ra-223; alpharadin previously) is currently one of the known drugs with proven effectiveness in relation to increasing overall survival of patients with CRPC. Ra-223 was developed specifically for patients with CRPC and symptomatic skeletal metastases. The drug targets the areas of skeletal tissue remodeling. Ra-223 is the therapy of choice in patients with CRPC and skeletal metastases and without confirmed visceral metastases before and after docetaxel chemotherapy. Chemotherapy after treatment with Ra-223 is a possible and satisfactory tolerable treatment option. Combination of Ra-223 with abiraterone, enzalutamide, or denosumab is, apparently, effective and safe, but further studies are necessary.

Prostate cancer (PC) is now one of the most common malignancies among men. Radical prostatectomy is the most commonly used therapy option for patients with localized PC. The appropriateness of surgical treatment for locally advanced and lymphogenic metastatic PC remains controversial, as the probability of non-radical intervention increases significantly and the risk for disease progression becomes higher. At the same time, interest in surgical treatment in patients with PC at high risk of progression, including those with lymphogenic metastases has recently increased greatly. There are more and more studies demonstrating improved survival rates in patients with high-risk PC, including those with distant metastases, who have undergone radical prostatectomy and lymphadenectomy compared with a cohort of patients who have received only drug therapy In addition to the studies evaluating the efficiency of neoadjuvant therapy before surgery in patients with localized or locally advanced high-risk PC, there are also investigations considering this option in PC patients with lymphogenic metastases. The paper gives the results of a clinical observation that shows the high efficiency of a multimodal approach with neoadjuvant chemohormonal therapy, followed by surgical treatment in a patient with lymphogenic metastatic PC.

The last decade was marked by the rapid development of kidney cancer drug treatment and advent of targeted drugs aimed at inhibition of angiogenesis which plays a crucial role in tumor growth. Despite certain success, targeted antiangiogenetic therapy with tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors (mTOR), and monoclonal antibodies against vascular endothelial growth factor (VEGF) in most cases do not achieve long-term remission, are highly toxic, and never lead to full cure for the patients. Development of modern immunological approaches to application of inhibitors of the crucial immune response regulators opens up new possibilities in treatment of disseminated kidney cancer. In this review, results of the studies of nivolumab (PD-1 inhibitor), first checkpoint inhibitor registered for treatment of metastatic kidney cancer are presented.