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Background: The Modified International Metastatic Renal Cell Carcinoma Dataset Consortium model (mIMDC) is a preoperative prognostic model for pT3cN0M0 renal cell carcinoma (RCC). This study aimed to validate the mIMDC and to construct a new model in a localized and locally advanced RCC (LLRCC). Methods: A database was established (the Michinoku Japan Urological Cancer Study Group database) consisting of 79 patients who were clinically diagnosed with LLRCC (cT3b/c/4NanyM0) and underwent radical nephrectomy from December 2007 to May 2018. Using univariable and multivariable analyses, we retrospectively analyzed disease-free survival (DFS) and overall survival (OS) in this database, constructed a new prognostic model according to these results, and estimated the model fit using c-index on the new and mIMDC models. Results: Independent poorer prognostic factors for both DFS and OS include the following: ≥ 1 Eastern Cooperative Oncology Group performance status, 2.0 mg/dL C-reactive protein, and > upper normal limit of white blood cell count. The median DFS in the favorable (no factor), intermediate (one factor), and poor-risk group (two or three factors) was 76.1, 14.3, and 4.0 months, respectively (P < 0.001). The 3-year OS in the favorable, intermediate, and poor-risk group were 92%, 44%, and 0%, respectively (P < 0.001). The c-indices of the new and mIMDC models were 0.67 and 0.60 for DFS (P = 0.060) and 0.74 and 0.63 for OS (P = 0.012), respectively. Conclusion: The new preoperative prognostic model in LLRCC can be used in patient care and clinical trials. [ABSTRACT FROM AUTHOR]

Background: This study is part of the SNPs in Nivolumab PD‐1 inhibitor for RCC (SNiP‐RCC). Here we aimed to reveal clinical factors for tumor response, progression, and survival in nivolumab for advanced clear cell renal cell carcinoma (RCC) in Japanese patients. Methods: We included patients from 23 institutions in Japan. We evaluated the objective response, radiographic progression‐free survival (PFS), overall survival (OS), and treatment‐related grade ≥ 3 (serious adverse events [SAEs]). Results: We included 222 patients. The median age was 69 years (interquartile range 62–74 years), and 71% of the patients were male. Pancreas metastasis, lung metastases, prior cytokine therapy, and SAEs, were associated with objective response. The median PFS was 18 months. Liver metastases (hazard ratio [HR], 1.61), age ≥ 75 (HR, 0.48), previous resection of primary sites (HR, 0.47), and SAEs (HR, 0.47) were independent prognostic factors for PFS. Karnofsky Performance Status <70 (HR, 2.90), high platelets (HR, 4.48), previous resection of primary sites (HR, 0.23), and pathological grade (HR, 0.19 for grade 2 and HR, 0.12 for grade 3) were independent prognostic factors for OS. SAEs were reported in 45 (20.3%) cases. In the group of patients with prior nephrectomy, SAEs were associated with objective response, PFS, and OS. Conclusion: The SNiP‐RCC study identified clinical parameters correlated with treatment outcomes in Japanese patients with priorly treated advanced clear cell RCC undergoing nivolumab monotherapy. [ABSTRACT FROM AUTHOR]

Background: We examined the relationship between the tumour microenvironment and the clinical efficacy of neoadjuvant chemotherapy in patients with cT2-4aN0M0 bladder cancer using multiplex fluorescence immunohistochemistry.Methods: The study retrospectively evaluated 51 patients who underwent radical cystectomy following neoadjuvant chemotherapy for cT2-4aN0M0 muscle-invasive bladder cancer. Patients were divided into responders (Results: The median age was 69 years; 39 patients were male. Twelve (23.5%), 17 (33.3%), 10 (19.7%) and 12 (23.5%) patients were pT0, pT1, pT2 and ≥pT3, respectively. Responders had a significantly higher 5-year cancer-specific survival rate (96.6%) than non-responders (48.4%; p = 0.0018). CD8+ T cell (p = 0.0056) and CD204+ cell (p = 0.0394) densities were significantly higher in the intratumoural area in non-responders than in responders. Patients with higher CD204+ cell densities in cancerous areas had worse prognosis.Conclusions: This comprehensive analysis of the immune microenvironment of a muscle-invasive bladder cancer specimen revealed that preexisting tumour-infiltrating proliferating CD8+ T cells and CD204+ cells are indicators of the response to neoadjuvant chemotherapy and that CD204+ cells can be considered an unfavourable prognostic factor in these patients. [ABSTRACT FROM AUTHOR]

A multicenter cooperative study was conducted to clarify the prognosis of Japanese patients with metastatic renal cell carcinoma in the era of molecular-targeted therapy and the clinical usefulness of the Japanese metastatic renal cancer ( JMRC) prognostic classification. Of 389 consecutive patients for whom treatment was started between 2008 and 2010 at 23 hospitals in Japan, 357 patients who received vascular endothelial growth factor receptor-tyrosine kinase inhibitor ( VEGFR- TKI) or cytokine as initial systemic therapy were the subject of the present study. Patients were classified into three prognostic groups according to the JMRC prognostic classification. The endpoints were progression-free survival ( PFS) and overall survival ( OS) after the start of the initial treatment. The median PFS and OS for the entire cohort of 357 patients were 9.1 and 27.2 months, respectively. VEGFR- TKI were selected for patients with multiple organ metastases, those with liver metastasis, and those with bone metastasis. The median PFS and OS were 11.0 and 23.2 months and 5.4 and 38.2 months in the VEGFR- TKI group and the cytokines group, respectively. The JMRC prognostic classification was useful as a prognostic model for PFS and OS (c-indexes: 0.613 and 0.630 in patients who initially received VEGFR- TKI and 0.647 and 0.642 in patients who received cytokines, respectively). The present study showed for the first time the prognosis of Japanese patients with metastatic renal cell carcinoma in the era of molecular-targeted therapy. The JMRC prognostic classification may be clinically useful as a prognostic model. [ABSTRACT FROM AUTHOR]

Purpose: We determined prognostic factors associated with prolonged survival after metastasectomy for urothelial carcinoma. Materials and Methods: A total of 42 patients who underwent resection of urothelial carcinoma metastases with curative intent at 4 Japanese university hospitals were included in analysis. Of the patients 41 of 42 underwent systemic chemotherapy before and/or after metastasectomy. Overall survival was analyzed using the Kaplan-Meier method. The relationship between clinical characteristics and survival was analyzed using the log rank test. Results: Metastasectomy included lymph node dissection in 20 cases, pulmonary resection in 12, pelvic exenteration in 3, resection of local recurrence in 2, resection of subcutaneous metastasis in 2, liver resection in 1 and other in 2. Median overall survival was 29 months (IQR 19–80) from the initiation of treatment for metastases and 26 months (IQR 11–90) from metastasectomy. The overall 5-year survival rate after metastasectomy was 31%. On univariate analysis patients treated with metastasectomy for a solitary lung or solitary lymph node metastasis had significantly longer survival than the others who underwent metastasectomy (81 vs 19 months, log rank test p = 0.0296). Conclusions: Long-term cancer control could be achieved in a subgroup of patients who undergo metastasectomy, especially those with a solitary lung or solitary lymph node metastasis. [Copyright &y& Elsevier]

Purpose: The active form of vitamin D3, that is 1α,25-dihydroxyvitamin D3, binds with vitamin D receptor, which forms a complex with retinoid X receptors α, β and γ to manifest antitumor effects. We examined the expression of vitamin D receptor and retinoid X receptors in renal cell carcinoma and elucidated the prognostic significance of these receptors. Materials and Methods: We performed immunohistochemical examination of vitamin D receptor, and retinoid X receptors α, β and γ in nephrectomized specimens of 68 patients with renal cell carcinoma. We analyzed the correlation between the expression of these receptors and clinicopathological parameters or patient survival. Mean followup was 68.2 months. Results: No significant correlation was found between the expression of vitamin D receptor, retinoid X receptor α or β and clinicopathological parameters. In contrast, retinoid X receptor γ expression correlated significantly with tumor stage (p = 0.009) and distant metastasis (p = 0.005). The 5-year cancer specific survival rate was higher in patients with retinoid X receptor γ positive renal cell carcinoma than those with retinoid X receptor γ negative renal cell carcinoma (79.3% vs 40.0%, p <0.05). Cox regression analysis revealed that retinoid X receptor γ expression, tumor status and lymph node status were significant independent prognostic factors in patients with renal cell carcinoma (p <0.05). A significant correlation was observed between the expression of retinoid X receptor γ and tumor stage, distant metastasis or the 5-year cancer specific survival rate. Furthermore, retinoid X receptor γ expression was an independent prognostic factor in patients with renal cell carcinoma. Conclusions: Our observations suggest that alterations of vitamin D receptor and retinoid X receptor expression may be involved in renal carcinogenesis and retinoid X receptor γ expression may be a useful prognostic marker in patients with renal cell carcinoma. [Copyright &y& Elsevier]

Aim: Biological and epidemiologic data suggest that 1 alpha, 25 dihydroxyvitamin D3 (1,25(OH)2D3) levels may influence development of renal cell carcinoma. The vitamin D receptor (VDR) is a crucial mediator for the cellular effects of 1,25(OH)2D3 and additionally interacts with other cell signaling pathways that influence cancer progression. VDR gene polymorphisms may play an important role in risk of incidence for various malignant tumors. This study investigated whether VDR gene polymorphisms were associated with increased risk and prognosis of renal cell carcinoma (RCC) in a Japanese population. Methods: To analyze risk of RCC depending on VDR polymorphism, a case–control association study was performed. The VDR gene polymorphisms at three locations, BsmI, ApaI and TaqI, were genotyped in 135 RCC patients and 150 controls in a Japanese population. Logistic regression models were used to assess the genetic effects on prognosis. Results: Significant differences in the ApaI genotype were observed between RCC patients and controls (χ2 = 6.90, P = 0.032). No statistical significant difference was found in the BsmI and TaqI polymorphisms. The frequency of the AA genotype in the ApaI polymorphism was significantly higher in the RCC patients than in the controls (odds ratio, 2.59; 95% confidence intervals, 1.21–5.55; P = 0.012). Multivariate regression analysis showed that the AA genotype was an independent prognostic factor for cause-specific survival (relative risk 3.3; P = 0.038). Conclusion: The AA genotype at the ApaI site of the VDR gene may be a risk of incidence and poor prognosis factor for RCC in the Japanese population. Additional studies with a large sample size and investigation of the functional significance of the ApaI polymorphism in RCC cells are warranted. [ABSTRACT FROM AUTHOR]