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Background/aim: CheckMate 214 study revealed that nivolumab plus ipilimumab combination therapy showed a strong and durable effect compared to sunitinib for patients with advanced renal cell carcinoma (aRCC). Most of the patients underwent previous nephrectomy before systemic treatment. We retrospectively investigated the clinical outcomes of Japanese patients treated with cytoreductive nephrectomy following nivolumab plus ipilimumab for aRCC., Patients and Methods: Seventy-nine patients were treated with systemic therapy for aRCC between October 2018 and August 2021 at the Saitama Medical University International Medical Center. Ten of 61 patients treated with nivolumab plus ipilimumab underwent cytoreductive nephrectomy after the combined immunotherapy., Results: The median overall survival and progression-free survival were 24.3 and 15.9 months, respectively. The objective response rate was 50.8%; 9.8% of patients had a complete response, and the median time to objective response was 3.2 (range=1.3-19.7) months. The estimated percentage of patients who sustained an objective response at 30 months was 73.0%. Twenty-three patients (74%) in the complete or partial response (CR/PR) group, 11 patients (52%) in the stable disease (SD) group, and two patients (22%) in the progressive disease (PD) group had immune-related adverse events of grade 3 or higher, respectively. For all 10 patients, cytoreductive nephrectomy following nivolumab plus ipilimumab treatment were completed safely. Three patients achieved a pathological complete response without viable cancer cells. Only two patients had residual lesions on images after deferred cytoreductive nephrectomy; the remaining patients achieved radiological CR., Conclusion: Cytoreductive nephrectomy after nivolumab plus ipilimumab treatment could be useful in a limited number of cases, possibly resulting in curative nephrectomy due to the durable therapeutic effect of immunotherapy., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: The objective of this study was to develop a novel prognostication model in patients with treatment-naïve metastatic renal cell carcinoma (mRCC)., Methods: This study included 325 consecutive mRCC patients receiving first-line molecular-targeted therapy at 4 institutions. Potential parameters associated with overall survival (OS) in these patients were investigated to develop a novel stratification model., Results: Median OS of the 325 patients was 38 months. A multivariable analysis of several factors identified independent predictors associated with unfavorable OS as follows: no previous nephrectomy, Karnofsky performance status <80%, albumin (Alb) ≤3.5 g/dl, C-reactive protein (CRP) >0.5 mg/dl and neutrophil-to-lymphocyte ratio (NLR) >3. Of these 5 independent OS predictors, 3 numeric factors were used to develop the ACN (Alb, CRP, and NLR) model by dividing patients into 3 groups according to the positive numbers of these 3 numeric risk factors. Median OS durations were 63, 37, and 11 months in the favorable (n = 105, 32.3%, without risk factors), intermediate (n = 88, 27.1%, with a single risk factor), and poor (n = 132, 40.6%, with multiple risk factors) risk groups, respectively. The ACN model as a prognostication tool was shown to be superior to the Memorial Sloan Kettering Cancer Center (MSKCC) and the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) models by both the concordance index and decision curve analysis., Conclusions: The ACN model could stratify the prognostic risk of mRCC patients receiving first-line targeted therapy more accurately than the MSKCC and IMDC models., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: We evaluated the impact of discontinuation of first-line (1L) molecular-targeted therapy on prognostic outcomes among patients with metastatic renal cell carcinoma (mRCC)., Methods: Study patients with mRCC were treated with 1L molecular-targeted agents at 4 separate institutions. Prognostic outcomes in this patient cohort were analyzed retrospectively based on whether discontinuation of 1L therapy was related to adverse events (AEs) or progression of disease (PD)., Results: Of the 201 patients enrolled, 117 patients (58%) and 84 patients (42%) discontinued 1L targeted therapy due to PD and AEs, respectively. Second-line therapy was subsequently provided to 101 (86%) and 66 (79%) of the patients who discontinued 1L therapy secondary to PD or AEs, respectively. Patients who discontinued 1L therapy due to AEs were significantly older than those with PD. The progression-free survival and overall survival from the initiation of 1L targeted therapy were significantly longer in patients who discontinued 1L therapy due to AE than in those who discontinued 1L therapy due to PD. The OS from the initiation of second-line targeted therapy was significantly longer in patients who discontinued 1L therapy due to AE than those with PD. Furthermore, AE as a reason for discontinuation of 1L targeted therapy as opposed to PD was independently associated with longer progression-free survival and OS as determined by multivariate analysis., Conclusions: Our findings suggest that mRCC patients who discontinue 1L therapy due to AEs have a more favorable prognosis than those who discontinue therapy due to PD., Competing Interests: Conflicts of interest The authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background/aim: The therapeutic outcomes of patients with metastatic renal cell carcinoma (mRCC) have dramatically improved with the introduction of molecular-targeted agents. The observational multicenter study was conducted to develop a novel stratification system for the intermediate risk group of the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model., Patients and Methods: The present study included 252 Japanese patients with mRCC who received first-line molecular-targeted therapy at four institutions., Results: The 252 patients were classified into the favorable, intermediate, and poor risk groups by the IMDC model. For the intermediate risk group, multivariate analysis of the six factors included in the IMDC model revealed that a low performance status, anemia, and a high platelet count were independent predictors of poor overall survival (OS). The intermediate risk group was subsequently divided into the following two groups (int -group 1 and 2) by the three independent OS predictors. Significant differences in the OS were noted among the IMDC favorable risk group, int-group 1, int-group 2, and poor risk group., Conclusion: The novel stratification presented in this study could be a useful tool for further prognostication of patients with mRCC classified into the intermediate risk group according to the IMDC model after first-line molecular-targeted therapy., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: International Metastatic Renal Cell Carcinoma Database Consortium model predicts the outcomes of metastatic renal cell carcinoma stratified into favorable, intermediate, and poor risk groups (FG, IG, and PG, respectively), with approximately 50% of patients being classified as IG. We aimed to generate better risk model based on the sub-classification of IG., Methods: We analyzed records of 213 consecutive patients receiving molecular targeted therapy. Age, gender, histology, type of initial molecular targeted therapy, serum laboratory data, previous nephrectomy and immunotherapy, and metastatic sites were used for IG sub-stratification. Modified and original models were compared using a concordance correlation coefficient analysis., Results: Median follow-up was 17.8 months. Serum albumin, serum C-reactive protein, and bone metastases were independent predictors of overall survival (OS) in IG. IG was sub-classified into low-, middle-, and high-risk IG according to the number of predictors. The following modified model was developed: modified FG (FG & low-risk IG), modified IG (middle-risk IG), and modified PG (PG & high-risk IG). Concordance indices for original and modified models were 0.68 and 0.73, respectively (P < 0.001). OS was significantly longer in modified PG treated with mammalian target of rapamycin inhibitors as second-line therapy than with tyrosine kinase inhibitors, whereas this was not observed in the original model., Conclusions: We successfully developed modified IMDC model using a two-step process: the original IMDC plus an IG sub-stratification, and demonstrated that it predicts outcomes more accurately than original model., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The objective of this prospective study was to identify baseline angiogenic and inflammatory markers in serum as well as the baseline levels of immune cells in whole blood to predict progression-free survival in patients with metastatic renal cell carcinoma treated with sunitinib. Blood samples were collected at baseline in all 90 patients to analyze serum angiogenic and inflammatory markers together with peripheral blood immunological marker. The association between each marker and sunitinib efficacy was analyzed. Univariate and multivariate Cox proportional model analyses were used to assess the correlation between those markers with survival. Baseline levels of interleukin-6, interleukin-8, high sensitivity C-reactive protein and myeloid-derived suppressor cells were significantly higher in patients who progressed when compared with those with clinical benefit. Analysis by the Cox regression model showed that baseline interleukin-8, high sensitivity C-reactive protein and percentage of T helper type 1 cells were significantly associated with progression-free survival in univariate analysis. Furthermore, in multivariate analysis, those three markers were independent indices to predict progression-free survival. In conclusion, angiogenic (interleukin-8), inflammatory (interleukin-6, high sensitivity C-reactive) and immunologic (myeloid-derived suppressor cells, percentage of T helper type 1 cells) markers at baseline would predict the response to sunitinib therapy and/or disease progression in patients with metastatic renal cell carcinoma., (© 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Purpose: The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk model has been designed for prognostification in patients with metastatic renal cell carcinoma (mRCC) treated with targeted therapy. One factor is neutrophil count; however, increasing evidence has suggested the superiority of neutrophil-to-lymphocyte ratio (NLR) for predicting outcome. In this study, we evaluate the prognostic effect of NLR levels on patients with mRCC treated with targeted therapy, and then we compare the predictive accuracy of the IMDC risk model and its modified one by using NLR, instead of neutrophil count., Patients and Method: A total of 277 patients are included for the analysis. All patients underwent targeted therapies and associated outcome are assessed using multivariate analysis., Results: Pretreatment NLR levels are elevated in 30.3% and 23.1% of patients in the first-line and subsequent second-line setting, respectively. Kaplan-Meier curves reveal that elevated pretreatment NLR is significantly associated with poor overall survival (OS) since first-line (P<0.001) and second-line targeted therapy administration (P<0.001). Also, multivariate analyses show that elevated pretreatment NLR is an independent predictor for poor OS since first-line and second-line targeted therapy administration. The addition of NLR to the IMDC risk model, instead of neutrophil count, significantly improves the predictive accuracy for OS, and estimated gain is 1.7% and 6.2% in first-line and second-line targeted therapy, respectively., Conclusion: Changes in NLR levels could be predictive for prognosis in patients with mRCC treated with first-line and second-line targeted therapy. The addition of NLR significantly improves the predictive accuracy of the IMDC risk model in the first-line and subsequent second-line setting., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Relative dose intensity (RDI) is a simple index for evaluation of the amount of drug administered per unit time. We retrospectively investigated the prognostic impact of RDI for patients with metastatic renal cell carcinoma (mRCC) treated with second-line targeted therapy., Methods: We enrolled 168 patients with mRCC. We assessed RDI at 4 weeks after second-line targeted therapy induction., Results: The median follow-up after second-line targeted therapy was 18.1 months. The median time-to-treatment-failure (TTF) and overall survival (OS) were 4.9 and 25.4 months, respectively. In the Kaplan-Meier analysis, the median OS of patients with second-line RDI < 0.7 was significantly shorter than those with RDI ≥ 0.7 (12.1 vs. 31.3 months; P = .030). In the subgroup analysis, second-line RDI was definitely prognostic in the poor-risk group of the International Metastatic Renal Cell Carcinoma Database Consortium criteria, showing second-line RDI was an independent predictor for both TTF (hazard ratio [HR], 3.6; 95% confidence interval [CI], 1.6-8.0; P = .002) and OS (HR, 3.1; 95% CI, 1.1-8.4; P = .026). Also, assessing the type of second-line regimen, the multivariate analysis showed that second-line RDI was an independent prognostic indicator of TTF (HR, 1.7; 95% CI, 1.0-2.9; P = .040) and OS (HR, 2.7; 95% CI, 1.3-5.7; P = .009) in patients treated with everolimus. In this group, the median TTF and OS of patients with RDI < 0.7 were 2.4 and 11.1 months, and those with RDI ≥ 0.7 were 5.3 and 25.9 months, respectively., Conclusion: The results suggest that second-line RDI may be a prognostic predictor for patients with mRCC treated with second-line targeted therapy, particularly in both the International Metastatic Renal Cell Carcinoma Database Consortium poor-risk group and everolimus-treated group., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: To investigate the impact of perioperative plasma fibrinogen level as a biomarker of oncological outcome in localised renal cell carcinoma (RCC)., Patients and Methods: We consecutively identified 601 patients with localised RCC who underwent curative surgery at a single institution. Subsequent disease recurrence and cancer-specific survival (CSS) were assessed using the Kaplan-Meier method. To evaluate the independent prognostic impact of plasma fibrinogen level, multivariate analysis was performed for these outcomes., Results: Using the defined threshold level of preoperative plasma fibrinogen of ≥420 mg/dL as elevated, we found 56 patients (9.3%) with an elevated plasma fibrinogen level preoperatively. In Kaplan-Meier analysis, there was a significant difference in disease-free survival and CSS rates between patients with and without preoperative plasma fibrinogen levels of ≥420 mg/dL. Multivariate analysis showed that elevated preoperative plasma fibrinogen level was an independent predictor of subsequent disease recurrence and cancer-specific mortality. In a subgroup analysis of the elevated preoperative plasma fibrinogen level group, postoperative normalisation of plasma fibrinogen level was significantly associated with CSS, showing that patients with non-normalised plasma fibrinogen levels tended to have a higher incidence of cancer-specific mortality after surgery., Conclusion: Patients with elevated preoperative plasma fibrinogen levels could be significantly predicted to have subsequent tumour metastasis and cancer-specific mortality, while there was a significant difference in CSS between patients in the normalised and non-normalised postoperative plasma fibrinogen groups. While these are hypothesis generating results, plasma fibrinogen levels may be a useful biomarker due to its low cost and ease of assessment., (© 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.)

Purpose: To investigate the prognostic effect of the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model reclassification after targeted therapy administration in metastatic renal cell carcinoma (mRCC)., Patients and Method: A total of 245 mRCC patients treated with targeted therapy are included. The IMDC model reclassification is performed at 1 month after treatment induction of both first-line and second-line targeted therapy., Results: Of the 245 patients, 74 (30.2%) are divided into different risk groups by the IMDC model reclassification after first-line targeted therapy, and patients newly classified with intermediate risk tend to have better overall survival than those remaining in the primary poor-risk group (P = 0.018). Of the 119 patients treated with subsequent second-line targeted therapy, 25 (21.0%) are divided into different risk groups by the IMDC model reclassification after second-line targeted therapy, and patients newly classified with poor risk tend to have increased all-cause mortality compared with those remaining in the primary intermediate-risk group (P = 0.007), whereas patients newly classified with intermediate risk tend to have better overall survival than those remaining in the primary poor-risk group (P = 0.034)., Conclusion: Approximately a quarter of the mRCC patients are classified into different risk groups of the IMDC model following targeted therapy administration in the first-line and second-line settings. There is a significant difference in overall survival of subgroups after the IMDC model reclassifications., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Current guidelines do not yet provide any recommendations for adjuvant chemotherapy in patients with upper tract urothelial carcinoma managed with radical nephroureterectomy. We evaluated whether an adjuvant chemotherapeutic regimen would affect the clinical outcome in patients with high risk upper tract urothelial carcinoma., Materials and Methods: We identified 873 patients who had undergone radical nephrouretectomy for localized upper tract urothelial carcinoma at 14 Japanese institutions between 1993 and 2011. We assessed whether the type of regimen, such as methotrexate, vinblastine, doxorubicin and cisplatin, and gemcitabine and cisplatin, in an adjuvant setting, could affect the subsequent clinical outcome of patients with upper tract urothelial carcinoma., Results: On multivariate analysis pathological T stage, tumor grade, lymphovascular invasion and lymph node involvement were prognostic factors for recurrence-free survival and cancer specific survival. We defined 229 patients with 3 or more of these factors as the high risk group. In an analysis according to adjuvant regimen, Kaplan-Meier curves showed that the 1 and 2-year recurrence-free survival rates in the methotrexate, vinblastine, doxorubicin and cisplatin treated group were 71.4% and 47.9%, which were significantly higher than in the gemcitabine and cisplatin treated group (48.2% and not reached, p=0.022) or those not treated with adjuvant chemotherapy (53.4% and 39.6%, p=0.039). Similar results were observed in terms of cancer specific survival., Conclusions: Our study showed that pT3-4, tumor grade 3, positive lymphovascular invasion and lymph node involvement were independent risk factors for disease mortality in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy. In the high risk group methotrexate, vinblastine, doxorubicin and cisplatin adjuvant chemotherapy contributed to improve subsequent mortality compared to gemcitabine and cisplatin or no adjuvant chemotherapy., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the site-specific pattern of disease recurrence and/or metastasis and the associated patient outcomes after radical nephroureterectomy (RNU) in upper tract urothelial carcinoma (UTUC)., Methods: A total of 733 patients with UTUC from a retrospective multi-institutional cohort were included, with a median follow-up of 34 months. Associated patient outcomes were analyzed by multivariate analysis. To evaluate the influence of primary tumor location, we divided it into four areas: renal pelvis, and upper, middle, and lower ureter., Results: A total of 218 patients experienced disease recurrence, with the majority of relapses occurring within the first 3 years. Cumulative incidence rates of first disease recurrence at 1 and 3 years were 18.9 and 29.8 %, respectively. Of these patients, 38.5 % developed distant recurrence; 17.4 % experienced both local and distant recurrences; and 44.0 % developed isolated local recurrence. The predominant sites of distant metastasis were lung, liver, and bone. Multivariate analysis revealed that the prevalence of local recurrence and lung metastasis was significantly associated, with primary tumor location being independent of other clinicopathological variables. Lower/middle ureter tumors had a higher rate of local recurrence in the pelvic cavity, and renal pelvic tumors had a higher prevalence of distant relapse in the lungs. Similar results were obtained when rerunning the data set by excluding patients who received adjuvant chemotherapy (n = 131)., Conclusions: This multi-institutional study provided a detailed picture of metastatic behavior after RNU, and primary tumor locations were associated with unique patterns of metastatic spread in UTUC patients.

Background: Few studies have discussed the prognostic impact of serum C-reactive protein (CRP) level in upper tract urothelial carcinoma (UTUC)., Objective: To investigate whether the perioperative level of CRP provides additional prognostic information following radical nephroureterectomy (RNU)., Design, Setting, and Participants: A total of 564 patients with UTUC from a retrospective multi-institutional cohort were included. The median follow-up was 32 mo., Intervention: All patients underwent RNU without neoadjuvant chemotherapy, while 106 patients (18.8%) received adjuvant chemotherapy., Outcome Measurements and Statistical Analysis: Associations between perioperative CRP level and outcome were assessed using multivariate analysis. A serum CRP level >0.50mg/dl was defined as elevated., Results and Limitations: Preoperative CRP (pre-CRP) level was elevated in 136 patients (24.1%). Multivariate analysis showed that pre-CRP elevation was an independent predictor of subsequent disease recurrence (hazard ratio [HR]: 1.47 for CRP 0.51-2.00; HR: 1.89 for CRP >2.00). Five-year recurrence-free survival rates were 69.2% in patients with pre-CRP levels ≤ 0.50 mg/dl, 54.3% in patients with pre-CRP levels between 0.51 and 2.00 mg/dl, and 35.4% in patients with pre-CRP levels >2.00 mg/dl (p<0.001). Similar results were found in cancer-specific mortality, showing that pre-CRP elevation was an independent predictor of worse outcome (HR: 1.74 for CRP 0.51-2.00; HR: 2.31 for CRP >2.00). In a subgroup analysis of the elevated pre-CRP group, postoperative normalisation of CRP level was an independent predictor of better outcome. This study is limited by its retrospective nature as well as its heterogeneous group of patients and variable follow-up protocols resulting from the multi-institution design., Conclusions: Serum CRP may become a possible biomarker in UTUC, suggesting that patients with an elevated pre-CRP level could be predicted to have subsequent disease recurrence and cancer-specific mortality, while postoperative normalisation of CRP level was an independent predictor for prognosis., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: To investigate oncological outcomes and prognostic factors in patients with upper tract urothelial carcinoma (UTUC) who experienced disease recurrence after radical nephroureterectomy (RNU). Few studies have focused on the clinical courses of patients who experienced disease recurrence after RNU., Patients and Methods: A total of 204 UTUC patients who experienced disease recurrence from a retrospective multi-institutional cohort were included in the present study. Associated patient outcomes were analyzed using multivariate analysis., Results: The mean time from RNU to first disease recurrence was 15.0 months and ≈90% of patients experienced disease recurrence within the first 3 years after RNU. During a median follow-up of 8.1 month after disease recurrence, 165 patients died from UTUC and five patients died from other causes. In the 204 cohorts, 1- and 3-year cancer-specific survival rates were 40.2% and 9.7%, respectively, and 1- and 3-year overall survival rates were 39.5% and 9.4%, respectively. After disease recurrence, 132 patients underwent systemic chemotherapy, and a subgroup analysis of patients who underwent systemic chemotherapy multivariate analysis showed that performance status, the presence of liver metastasis and the number of recurrence sites were independently prognostic of cancer-specific and overall survival after relapsing. According to three significant variables, 1- and 3-year cancer-specific survival rates were 72.7% and 20.8% in patients with no risk factors, 46.5% and 7.5% in patients with one risk factor, and 26.4% and 4.4% in patients with two or three risk factors, respectively (P < 0.001)., Conclusions: Most patients died from UTUC within 3 years, even though systemic chemotherapies were administered after relapsing. Multivariate analysis showed that performance status, the presence of liver metastasis and the number of recurrence sites were independently related to poor survival after systemic chemotherapy., (© 2013 BJU International.)

Objective: A reliable prognostic indicator in patients with pathologic T1a renal cell carcinoma has not yet been fully elucidated. The aim of this study was to investigate the prognosis of pathologic T1a renal cell carcinoma cases with a special focus on pathological factors., Methods: The study population consisted of 338 patients diagnosed with solitary renal cell carcinoma at our hospital between 1996 and 2009. The relationship between disease progression and clinicopathologic features was analyzed retrospectively to determine if it affected recurrence and distant metastasis., Results: The Fuhrman nuclear grade distribution between the tumors was 1, 2, 3 and 4 in 68 (20.1%), 242 (71.6%), 21 (6.2%) and 7 cases (2.1%), respectively. A total of 11 subjects were identified as having recurrent tumors (3.3%), 9 of whom had metastatic lesions. Multivariate analysis showed that the appearance of tumor Grade 3 and 4 (hazard ratio: 13.0, 95% confidence interval: 3.90-43.0, P < 0.001) was an independent risk factor for tumor recurrence, while no significant correlation was found between tumor recurrence and age, gender, tumor side, tumor size, surgical methods, histology, microvascular invasion or surgical margin status. The 5-year recurrence-free survival rate was 67.8% in patients with a high nuclear grade tumor, and 96.8% in their counterparts., Conclusions: High nuclear grade is possibly one of the most important prognostic factors for predicting tumor recurrence and metastasis after surgery in pathologic T1a renal cell carcinoma. Thus, careful follow-up may be required in patients with pathologic T1a renal cell carcinoma of a high nuclear grade.

Purpose: Recently several prognostic nomograms have been developed to predict the prognosis of malignant diseases, including renal cell carcinoma. However, to our knowledge a preoperative prognostic nomogram that predicts survival in patients with renal cell carcinoma is not available. We developed a preoperative nomogram based on the TNM classification that predicts cause specific survival in patients with renal cell carcinoma., Materials and Methods: A total of 545 patients with renal cell carcinoma, including metastatic disease, who underwent radical nephrectomy or nephron sparing surgery at our institution were included in the study. Cases were staged according to the 2002 UICC TNM system, 6th edition. T, N and M factors were used as prognostic factors and a Cox proportional hazards regression model was developed to predict cause specific survival. A nomogram to predict cause specific survival was developed by repeating the analysis on 200 bootstrap samples. To validate the nomogram a concordance index was estimated and calibration was also examined by plotting the predictions made by the nomogram., Results: Overall 1, 3 and 5-year patient survival was 95.2%, 92.0% and 89.9%, respectively. T, N and M factors were significant prognostic factors in the Cox proportional hazards regression model. Using the combined TNM factors we developed a nomogram predicting 1, 3 and 5-year cause specific survival rates. The nomogram had excellent ability to discriminate, as evidenced by a concordance index of 0.81, and it was generally well calibrated., Conclusions: The preoperative information shown by this nomogram may be important for obtaining informed consent from patients with renal cell carcinoma who have indications for surgery.

Purpose: Recent studies suggest that alterations in chromatin structure by histone acetylation may have an important role in the neoplastic process. We evaluated histone H3 acetylation in renal cell carcinoma and the effects of a histone deacetylase inhibitor on renal cancer cell lines., Materials and Methods: The expression of acetylated histone H3 (Lys9) in renal cell carcinoma and corresponding nonneoplastic tissue specimens was evaluated. We next assessed immunohistologically the relationships between acetylated histone H3 expression and clinicopathological parameters in 44 cases of renal cell carcinoma. Furthermore, we evaluated the effects of the histone deacetylase inhibitor depsipeptide on the renal cancer cell lines Caki-1, ACHN, 769P and 786O (ATCC)., Results: Acetylated histone H3 expression was decreased in 85.0% of renal cell carcinomas compared to levels in nonneoplastic tissue. Decreased expression was related to high nuclear tumor grade and advanced pathological tumor stage (p = 0.048 and 0.032, respectively). Depsipeptide inhibited cell line proliferation in a time and dose dependent manner. Depsipeptide induced apoptosis in Caki-1, ACHN and 786O, and induced G2 cell cycle arrest in 769P. Concomitantly depsipeptide increased acetylated histone H3 and p21(WAF/CIP1) expression, and induced Bcl-2 phosphorylation., Conclusions: These results suggest that the decreased acetylation of histone H3 is a common alteration in a malignant phenotype of renal cell carcinoma. Increasing the amount of acetylated histone H3 might be a therapeutic option for renal cell carcinoma.