The role of adjuvant treatment in high-risk muscle-invasive urothelial carcinoma after radical surgery is not clear. In a phase 3, multicenter, double-blind, randomized, controlled trial, we assigned patients with muscle-invasive urothelial carcinoma who had undergone radical surgery to receive, in a 1:1 ratio, either nivolumab (240 mg intravenously) or placebo every 2 weeks for up to 1 year. Neoadjuvant cisplatin-based chemotherapy before trial entry was allowed. The primary end points were disease-free survival among all the patients (intention-to-treat population) and among patients with a tumor programmed death ligand 1 (PD-L1) expression level of 1% or more. Survival free from recurrence outside the urothelial tract was a secondary end point. A total of 353 patients were assigned to receive nivolumab and 356 to receive placebo. The median disease-free survival in the intention-to-treat population was 20.8 months (95% confidence interval [CI], 16.5 to 27.6) with nivolumab and 10.8 months (95% CI, 8.3 to 13.9) with placebo. The percentage of patients who were alive and disease-free at 6 months was 74.9% with nivolumab and 60.3% with placebo (hazard ratio for disease recurrence or death, 0.70; 98.22% CI, 0.55 to 0.90; P<0.001). Among patients with a PD-L1 expression level of 1% or more, the percentage of patients was 74.5% and 55.7%, respectively (hazard ratio, 0.55; 98.72% CI, 0.35 to 0.85; P<0.001). The median survival free from recurrence outside the urothelial tract in the intention-to-treat population was 22.9 months (95% CI, 19.2 to 33.4) with nivolumab and 13.7 months (95% CI, 8.4 to 20.3) with placebo. The percentage of patients who were alive and free from recurrence outside the urothelial tract at 6 months was 77.0% with nivolumab and 62.7% with placebo (hazard ratio for recurrence outside the urothelial tract or death, 0.72; 95% CI, 0.59 to 0.89). Among patients with a PD-L1 expression level of 1% or more, the percentage of patients was 75.3% and 56.7%, respectively (hazard ratio, 0.55; 95% CI, 0.39 to 0.79). Treatment-related adverse events of grade 3 or higher occurred in 17.9% of the nivolumab group and 7.2% of the placebo group. Two treatment-related deaths due to pneumonitis and one treatment-related death due to bowel perforation were noted in the nivolumab group. In this trial involving patients with high-risk muscle-invasive urothelial carcinoma who had undergone radical surgery, disease-free survival was longer with adjuvant nivolumab than with placebo in the intention-to-treat population and among patients with a PD-L1 expression level of 1% or more. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 274 ClinicalTrials.gov number, NCT02632409.)

PD-1/PD-L1 axis plays an important role in maintaining homeostasis and prevention from autoimmunity; however, in the tumor microenvironment, PD-1/PD-L1 interaction is responsible for the evasion of immune surveillance by tumor cells. We therefore hypothesized that single nucleotide polymorphisms (SNPs) in genes encoding PD-1 and PD-L1 molecules are associated with the development and outcome of renal cell carcinoma (RCC). Here we genotyped nine polymorphisms: five of PDCD1: rs36084323G>A, rs11568821G>A, rs2227981C>T, rs10204525G>A, rs7421861T>C and four of PD-L1: rs822335C>T, rs4143815G>C, rs4742098A>G, rs10815225G>C in 237 RCC patients (including 208 with clear cell RCC (ccRCC)) and 256 controls, with application of allelic discrimination method with use of TaqMan Assays. Interestingly, we found the SNP-SNP interaction between rs10815225 and rs7421861 polymorphisms associated with ccRCC risk. The rs7421861 TC genotype decreased the risk of ccRCC development compared to TT and CC genotypes in the group of rs10815225 GC + CC individuals (OR = 0.21, CI95% = 0.08; 0.54). While possessing of rs10815225 GC or CC genotype increased susceptibility to ccRCC when compared to rs10815225 GG genotype in individuals with rs7421861 TT or CC genotype (OR = 2.40, CI95% = 1.25; 4.61). In conclusion, genetic variants in PDCD1 and PD-L1 genes, especially taken together as SNP-SNP interactions, can be considered to be ccRCC risk factors.

Renal cell cancer is the most common type of kidney cancer in adults, and clear cell renal cell carcinoma (ccRCC) is the most diagnosed type. T cell immunoglobulin and mucin-domain-containing-3 (TIM-3) belongs to immunological checkpoints that are key regulators of the immune response. One of the known TIM-3 ligands is galectin-9 (LGALS9). A limited number of studies have shown an association between TIM-3 polymorphisms and cancer risk in the Asian population; however, there is no study on the role of LGALS9 polymorphisms in cancer. The present study aimed to analyze the influence of TIM-3 and LGALS9 polymorphisms on susceptibility to ccRCC and patient overall survival (OS), with over ten years of observations. Using TaqMan probes, ARMS–PCR, and RFPL-PCR, we genotyped two TIM-3 single-nucleotide polymorphisms (SNPs): rs1036199 and rs10057302, and four LGALS9 SNPs: rs361497, rs3751093, rs4239242, and rs4794976. We found that the presence of the rs10057302 A allele (AC + AA genotypes) as well as the rs4794976 T allele (GT + TT genotypes) decreased susceptibility to ccRCC by two-fold compared to corresponding homozygotes. A subgroup analysis showed the association of some SNPs with clinical features. Moreover, TIM-3 rs1036199 significantly influenced OS. Our results indicate that variations within TIM-3 and LGALS9 genes are associated with ccRCC risk and OS.

Lowering morbidity and mortality after RC is subject of considerable interest. Lately, many evidence-based data on improvements in operative technique, anesthetic management, and patient care have been published. In this article, we present a review of literature on how to lower postoperative complications after RC. The Medline, and Web of Science databases were searched without a time limit on February 2016 using the terms 'cystectomy' in conjunction with 'radical', 'bladder cancer', 'complications' or 'management'. Boolean operators (NOT, AND, OR) were also used in succession to narrow and broaden the search. The search was limited to the English, Polish and Spanish literature. Many complications may be avoided by appropriate patient selection and meticulous introduction of care protocols. RC as treatment free of complications, even in the hands of an experienced urologist, does not exist. A large number of complications are acceptable in the name of good long-term results. Optimum results are possible with proper surgical technique, good patients and urinary diversion selection and proper patient management in the pre-, peri, and postoperative period.

Renal arterial embolization (RAE) is one of the adjunctive methods in the treatment of renal tumors. Embolization is performed in patients prior to nephrectomy, in patients with inoperable renal tumors as palliative treatment. The purpose of the study was to present and to analyze our own experiences in the embolization of renal tumors. A retrospective analysis of 33 patients treated using RAE between 2011 and 2013 was carried out. In 30 cases (91%), embolization was performed due to renal carcinoma and in 3 cases (9%) due to angiomyolipoma. In 11 patients intervention was performed as a palliative procedure because of advanced disease. Histoacrylic glue, polyvinyl alcohol, sponge pledgets and embolization coils were used for embolization. In 20 patients (61%), selective RAE was performed, whereas superselective RAE was carried out in 13 patients (39%). The technical success rate of RAE was 100%. In one case the procedure was complicated by reflux of the histoacrylic glue into the common femoral artery with its embolization that required surgical embolectomy. We used histoacrylic glue in 26 embolizations (79%), in 19 procedures (58%) as the only embolization agent. Polyvinyl alcohol was used in 10 procedures (30%), gelatin sponge pledgets and absolute ethanol in 6 patients (18%). In 4 cases (12%), coils were implemented. In 22 patients (67%), one or more components of postembolization syndrome (PES) developed. In all 22 patients with PES (100%), severe lumbar pain was observed and administration of analgesics proved necessary. In 10 patients treated by palliative embolization, both a regression of macrohaematuria and an increase in hemoglobin level were observed. In 10 further patients, the creatinine level decreased following RAE. RAE is an effective and minimally-invasive intervention burdened with low risk of major complications. PES occurs in about two-third of patients. In the majority of patients after palliative embolization, haematuria decreases and the quality of life improves.

Renal cell carcinoma (RCC) accounts for approximately 90–95% of all kidney cancers in adults, with clear cell RCC (ccRCC) being the most frequently identified subtype. RCC is known for its responsiveness to immunotherapy, making it an area of significant research interest. Immune checkpoint (IC) molecules, which regulate immune surveillance, are established therapeutic targets in RCC. The aim of this study was to analyze the influence of HVEM and CD160 gene polymorphisms on ccRCC susceptibility and patient overall survival (OS) over a ten-year period of observation. We genotyped three HVEM single nucleotide polymorphisms (SNPs): rs1886730, rs2234167, and rs8725, as well as two CD160 SNPs: rs744877 and rs2231375, in 238 ccRCC patients and 521 controls. Our findings indicated that heterozygosity within rs2231375 and/or rs2234167 increases ccRCC risk. Furthermore, in women, heterozygosity within HVEM SNPs rs8725 and rs1886730 is also associated with an increased ccRCC risk. The presence of a minor allele for rs1886730, rs2234167, rs8725, and rs2231375 was also correlated with certain clinical features of ccRCC. Moreover, rs1886730 was found to be associated with OS. In conclusion, our study highlights an association between HVEM and CD160 polymorphisms and the risk of developing ccRCC as well as OS.