Preoperative fibrinogen/CRP score predicts survival in upper urothelial tract carcinoma patients undergoing radical curative surgery.

PURPOSE: Upper tract urothelial carcinoma (UTUC) represents an often aggressive malignancy associated with poor prognosis. Therefore, finding reliable prognostic biomarkers in patients undergoing curative surgery for improved risk stratification is crucial. We evaluated the prognostic value of the Fibrinogen/C-reactive protein (FC)-score in a cohort of surgically treated UTUC patients. METHODS: 170 patients with radiologically and histologically verified UTUC who underwent radical curative surgery between 1990 and 2020, were included. The FC-score was calculated for each patient, with patients receiving 1 point each if Fibrinogen and/or CRP levels were elevated above the 25th or 75th percentile, respectively. Patients were divided into three subgroups according to their FC-score of 0, 1 or 2 point(s). Kaplan-Meier analysis, uni- and multivariable Cox proportional hazard models were implemented. We determined cancer-specific survival (CSS) as primary endpoint, whereas overall survival (OS) and recurrence-free survival (RFS) were considered secondary endpoints. RESULTS: High FC-score (2 points) was significantly associated with adverse histological features such as vascular invasion (OR = 4.08, 95%CI 1.18-14.15, p = .0027) and tumour necrosis (OR = 6.67, 95%CI 1.35-32.96, p = 0.020). Both, uni- and multivariable Cox proportional hazard models showed the FC-score as a significant predictor for CSS (univariable analysis: FC-score = 1: HR = 1.90, 95%CI 0.92-3.93, p = 0.085 | FC-score = 2: HR = 2.86, 95%CI 1.22-6.72, p = 0.016). Furthermore, in univariable analysis, patients with higher FC-score had significantly shorter OS (FC-score = 1: HR = 1.32, 95%CI 0.70-2.49, p = 0.387 | FC-score = 2: HR = 2.19, 95%CI 1.02-4.67, p = 0.043). However, this did not prevail in multivariable analysis. CONCLUSION: The FC-score represents a novel potential biomarker in patients with UTUC undergoing radical curative surgery.

Long-Term Results after Suprapubic ARC Procedure for the Treatment of Stress Urinary Incontinence in Women: A Retrospective Data Analysis.

INTRODUCTION: The aim of this study was to evaluate long-term safety and efficacy of the suprapubic arc (SPARC) procedure for the surgical treatment of stress urinary incontinence (SUI). MATERIALS AND METHODS: 139 female patients treated by SPARC were included in this retrospective analysis, whereby 126 patients were available for follow-up after 1 year, 70 after 6 years, and 41 after 9 years. The cough test, pad test, uroflowmetry, and post-void residual volume measurements were performed. Severity of bother (visual analogous scale [VAS] 0-10), continence, and the satisfaction rate were assessed. Objective cure was defined as a negative cough test and pad weight ≤1 g, subjective cure as no urine loss during daily activities and no usage of pads. The VAS, pad weight, number of pads per day, and maximal flow rate were compared preoperatively and postoperatively. RESULTS: Objective cure rates at 1, 6, and 9 years were 78.6, 71.4, and 70.7% and subjective cure rates were 72.2, 55.7, and 65.8%, respectively. The VAS, pad weight, number of pads, and maximal flow rate decreased significantly. Study limitations include a relatively small sample size and the retrospective fashion of the analysis. CONCLUSIONS: In the long-term context, SPARC showed to represent an efficient and safe procedure for treatment of female SUI.

Special Issue on Molecular Research Efforts in Urothelial Carcinoma: Summary of Included Topics.

This Special Issue of International Journal of Molecular Sciences (IJMS) covers one of the most intriguing and emerging fields in terms of molecular oncology and uro-oncologic research efforts over the recent years, namely urothelial carcinoma of the bladder (UCB), as well as urothelial carcinoma of the upper urinary tract (UTUC). A total of 8 articles published in this Special Issue highlight the current progress in molecular oncology and cancer genetics in UCB, including a wide range of research topics, such as FGFR-inhibitors, sarcopenia in UCB, molecular predictors of response following neoadjuvant chemotherapy, exercise cardiac training impacts in the murine UCB model, Obatoclax, tropomyosins as potential biomarkers, immunotherapeutic approaches, as well as a transcriptional analysis of immunohistochemically defined UCB-subgroups. Find a brief summary of the respective articles below.

MiR-371a-3p Serum Levels Are Increased in Recurrence of Testicular Germ Cell Tumor Patients.

Metastatic testicular germ cell tumors (TGCTs) are a potentially curable disease by administration of risk-adapted cytotoxic chemotherapy. Nevertheless, a disease-relapse after curative chemotherapy needs more intensive salvage chemotherapy and significantly worsens the prognosis of TGCT patients. Circulating tumor markers (ß-subunit of human chorionic gonadotropin (ß-HCG), alpha-Fetoprotein (AFP), and Lactate Dehydrogenase (LDH)) are frequently used for monitoring disease recurrence in TGCT patients, though they lack diagnostic sensitivity and specificity. Increasing evidence suggests that serum levels of stem cell-associated microRNAs (miR-371a-3p and miR-302/367 cluster) are outperforming the traditional tumor markers in terms of sensitivity to detect newly diagnosed TGCT patients. The aim of this study was to investigate whether these miRNAs are also informative in detection of disease recurrence in TGCT patients after curative first line therapy. For this purpose, we measured the serum levels of miR-371a-3p and miR-367 in 52 samples of ten TGCT patients at different time points during disease relapse and during salvage chemotherapy. In our study, miR-371a-3p levels in serum samples with proven disease recurrence were 13.65 fold higher than levels from the same patients without evidence of disease (p = 0.014). In contrast, miR-367 levels were not different in these patient groups (p = 0.985). In conclusion, miR-371a-3p is a sensitive and potentially novel biomarker for detecting disease relapse in TGCT patients. This promising biomarker should be investigated in further large prospective trials.

Critical evaluation of the potential prognostic value of the pretreatment-derived neutrophil-lymphocyte ratio under consideration of C-reactive protein levels in clear cell renal cell carcinoma.

BACKGROUND: We investigated the prognostic value of the pretreatment-derived neutrophil-lymphocyte ratio (dNLR) and original NLR in relation to the commonly used inflammation marker C-reactive protein (CRP) in a large cohort of patients with clear cell renal cell carcinoma (RCC). METHODS: Clinicopathological data from 587 consecutive non-metastatic clear cell RCC patients, operated between 2000 and 2010 at a single tertiary academic center, were evaluated retrospectively. Patients were categorised according to a cutoff value derived from receiver operating curve analysis. Overall (OS), cancer-specific (CSS) as well as metastasis-free survival (MFS) were assessed using the Kaplan-Meier method and multivariate Cox proportional models were applied. Spearman's rank correlation coefficient tested the association between dNLR and other markers of the systemic inflammatory response. RESULTS: The significant correlation between pretreatment NLR and dNLR was strong (ρ=0.84), whereas between dNLR and CRP it was weak (ρ=0.18). In multivariate analyses, dNLR achieved independent predictor status regarding CSS (P=0.037) and MFS (P=0.041), whereas CRP was confirmed as independent predictor of OS (P=0.010), CSS (P=0.039) and MFS (P=0.005), respectively. The NLR failed to reach independent predictor status regarding OS, CSS and MFS when CRP was included into the multivariate model. CONCLUSIONS: In the cohort studied, an elevated (⩾10.0) pretreatment CRP level and elevated dNLR (>2) were robust independent predictors of CSS and MFS. Our data suggest that CRP might be superior to both NLR and dNLR.

Blood Platelet Volume Represents a Novel Prognostic Factor in Patients with Nonmetastatic Renal Cell Carcinoma and Improves the Predictive Ability of Established Prognostic Scores.

PURPOSE: The average size of blood platelets determined by mean platelet volume might represent a biologically meaningful parameter in carcinogenesis and potentially serve as a novel prognostic biomarker in renal cell carcinoma. MATERIALS AND METHODS: In this retrospective analysis of the records of 652 patients we evaluated the potential prognostic value of mean platelet volume and its ability to improve existing risk assessment tools used in adjuvant clinical trials in nonmetastatic renal cell carcinoma cases. Associations of mean platelet volume with baseline covariates and clinical outcomes (recurrence, and death from renal cell carcinoma and other causes) were assessed with the competing risk estimators of Kaplan-Meier, and Marubini and Valsecchi, respectively. Univariable and multivariable Cox proportional hazard models were constructed. The Harrell c-index was applied to test improvements in the predictive accuracy of the established Leibovich prognosis score. RESULTS: Small platelet volume was associated with large tumors (p = 0.043), high Fuhrman grade (p = 0.001), sarcomatoid components (p <0.0001), histological tumor necrosis (p = 0.044) and vascular invasion (p = 0.022). On univariable and multivariable analyses small platelet volume accurately predicted recurrent renal cell carcinoma (continuously and binary coded) and cancer specific survival. Adding mean platelet volume to the Leibovich prognosis score improved its discriminative performance (c-index = 0.83, p = 0.004). CONCLUSIONS: Mean platelet volume represented a highly significant predictor of recurrence and cancer specific death in patients with renal cell carcinoma. This parameter improved the accuracy of the Leibovich prognosis score to better predict long-term outcomes in localized renal cell carcinoma cases after curative surgical resection.

Validation of the Preoperative Platelet-to-Lymphocyte Ratio as a Prognostic Factor in a European Cohort of Patients with Upper Tract Urothelial Carcinoma.

INTRODUCTION: This study is aimed at investigating the potential prognostic impact of the preoperatively assessed platelet-to-lymphocyte ratio (PLR) in a European cohort of patients with non-metastatic upper tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: Clinicopathological data from 180 consecutive non-metastatic UTUC patients, operated between 1990 and 2012 at a single tertiary academic center, were evaluated retrospectively. The preoperative PLR was assessed one day before surgery. Patients were categorized using a PLR cut-off value according to receiver-operating curve analysis. Cancer-specific survival (CSS) and overall survival (OS) were assessed using the Kaplan-Meier method. Additionally, multivariate proportional Cox regression models were applied. RESULTS: In multivariate analyses, age at the date of surgery (<65 vs. ≥65 years, hazard ratio (HR) 1.827, 95% CI 1.051-3.175, p = 0.033), pathologic T-stage (pT1 vs. pT2-4, HR 1.873, 95% CI 1.066-3.292, p = 0.029), and pretreatment PLR (<150.0 vs. ≥150.0, HR 1.782, 95% CI 1.041-3.050, p = 0.035) were independent predictors of OS. Regarding CSS, pathologic T-stage (pT1 vs. pT2-4, HR 2.176, 95% CI 1.062-4.460, p = 0.034) and pretreatment PLR (<150.0 vs. ≥150.0, HR 2.026, 95% CI 1.045-3.930, p = 0.037) were considered independent predictors. CONCLUSIONS: In the cohort studied, patients with an elevated (≥150.0) preoperative PLR had a higher cancer-specific mortality and overall mortality after radical surgery for UTUC, compared with those with a low pretreatment PLR.

MicroRNAs Associated with Von Hippel-Lindau Pathway in Renal Cell Carcinoma: A Comprehensive Review.

Renal cell carcinoma (RCC) are the most common renal neoplasia and can be divided into three main histologic subtypes, among which clear cell RCC is by far the most common form of kidney cancer. Despite substantial advances over the last decade in the understanding of RCC biology, surgical treatments, and targeted and immuno-therapies in the metastatic setting, the prognosis for advanced RCC patients remains poor. One of the major problems with RCC treatment strategies is inherent or acquired resistance towards therapeutic agents over time. The discovery of microRNAs (miRNAs), a class of small, non-coding, single-stranded RNAs that play a crucial role in post-transcriptional regulation, has added new dimensions to the development of novel diagnostic and treatment tools. Because of an association between Von Hippel-Lindau (VHL) genes with chromosomal loss in 3p25-26 and clear cell RCC, miRNAs have attracted considerable scientific interest over the last years. The loss of VHL function leads to constitutional activation of the hypoxia inducible factor (HIF) pathway and to consequent expression of numerous angiogenic and carcinogenic factors. Since miRNAs represent key players of carcinogenesis, tumor cell invasion, angiogenesis, as well as in development of metastases in RCC, they might serve as potential therapeutic targets. Several miRNAs are already known to be dysregulated in RCC and have been linked to biological processes involved in tumor angiogenesis and response to anti-cancer therapies. This review summarizes the role of different miRNAs in RCC angiogenesis and their association with the VHL gene, highlighting their potential role as novel drug targets.

Current Insights into Long Non-Coding RNAs in Renal Cell Carcinoma.

Renal cell carcinoma (RCC) represents a deadly disease with rising mortality despite intensive therapeutic efforts. It comprises several subtypes in terms of distinct histopathological features and different clinical presentations. Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts in the genome which vary in expression levels and length and perform diverse functions. They are involved in the inititation, evolution and progression of primary cancer, as well as in the development and spread of metastases. Recently, several lncRNAs were described in RCC. This review emphasises the rising importance of lncRNAs in RCC. Moreover, it provides an outlook on their therapeutic potential in the future.

Current Status of Long Non-Coding RNAs in Human Breast Cancer.

Breast cancer represents a major health burden in Europe and North America, as recently published data report breast cancer as the second leading cause of cancer related death in women worldwide. Breast cancer is regarded as a highly heterogeneous disease in terms of clinical course and biological behavior and can be divided into several molecular subtypes, with different prognosis and treatment responses. The discovery of numerous non-coding RNAs has dramatically changed our understanding of cell biology, especially the pathophysiology of cancer. Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts >200 nucleotides in length. Several studies have demonstrated their role as key regulators of gene expression, cell biology and carcinogenesis. Deregulated expression levels of lncRNAs have been observed in various types of cancers including breast cancer. lncRNAs are involved in cancer initiation, progression, and metastases. In this review, we summarize the recent literature to highlight the current status of this class of long non-coding lncRNAs in breast cancer.

Comprehensive Analysis of miRNome Alterations in Response to Sorafenib Treatment in Colorectal Cancer Cells.

MicroRNAs (miRNAs) are master regulators of drug resistance and have been previously proposed as potential biomarkers for the prediction of therapeutic response in colorectal cancer (CRC). Sorafenib, a multi-kinase inhibitor which has been approved for the treatment of liver, renal and thyroid cancer, is currently being studied as a monotherapy in selected molecular subtypes or in combination with other drugs in metastatic CRC. In this study, we explored sorafenib-induced cellular effects in Kirsten rat sarcoma viral oncogene homolog olog (KRAS) wild-type and KRAS-mutated CRC cell lines (Caco-2 and HRT-18), and finally profiled expression changes of specific miRNAs within the miRNome (>1000 human miRNAs) after exposure to sorafenib. Overall, sorafenib induced a time- and dose-dependent growth-inhibitory effect through S-phase cell cycle arrest in KRAS wild-type and KRAS-mutated CRC cells. In HRT-18 cells, two human miRNAs (hsa-miR-597 and hsa-miR-720) and two small RNAs (SNORD 13 and hsa-miR-3182) were identified as specifically sorafenib-induced. In Caco-2 cells, nine human miRNAs (hsa-miR-3142, hsa-miR-20a, hsa-miR-4301, hsa-miR-1290, hsa-miR-4286, hsa-miR-3182, hsa-miR-3142, hsa-miR-1246 and hsa-miR-720) were identified to be differentially regulated post sorafenib treatment. In conclusion, we confirmed sorafenib as a potential anti-neoplastic treatment strategy for CRC cells by demonstrating a growth-inhibitory and cell cycle-arresting effect of this drug. Changes in the miRNome indicate that some specific miRNAs might be relevant as indicators for sorafenib response, drug resistance and potential targets for combinatorial miRNA-based drug strategies.

The Preoperative AST/ALT (De Ritis) Ratio Represents a Poor Prognostic Factor in a Cohort of Patients with Nonmetastatic Renal Cell Carcinoma.

PURPOSE: Aminotransaminases, which are strongly involved in cellular metabolism and cancer cell turnover, represent easily measureable, potential blood based biomarkers. We evaluated the prognostic value of the preoperatively assessed AST/ALT (De Ritis) ratio on clinically meaningful end points in a large European cohort of patients with nonmetastatic renal cell carcinoma. MATERIALS AND METHODS: We retrospectively evaluated clinicopathological data on 698 patients with nonmetastatic renal cell carcinoma operated on between 2005 and 2013 at a single tertiary academic center. The potential prognostic value of the AST/ALT ratio was analyzed using the Kaplan-Meier method, and univariate and multivariate Cox proportional regression models. The impact of the ratio on the predictive accuracy of the Leibovich prognosis score was determined by the Harrell c-index. RESULTS: An increased (1.26 or greater) preoperative AST/ALT ratio was statistically significantly associated with several well established prognostic factors, including pathological T stage, as well as with histological tumor necrosis (p <0.05). On multivariate analysis an increased preoperative AST/ALT ratio was an independent prognostic factor for metastasis-free survival (HR 1.61, 95% CI 1.25-2.07, p <0.001) and overall survival (HR 1.76, 95% CI 1.34-2.32, p <0.001). The Harrell c-index was 0.77 using the Leibovich prognosis score and 0.81 when AST/ALT was added. CONCLUSIONS: In our study cohort with nonmetastatic renal cell carcinoma the preoperatively assessed AST/ALT ratio represented an independent prognostic factor. This ratio might further improve the predictive accuracy of well established prognosis scores.

Validation of the preoperative plasma fibrinogen level as a prognostic factor in a European cohort of patients with localized upper tract urothelial carcinoma.

PURPOSE: Fibrinogen is thought to have a potentially significant role in the progression and metastatic spread of different human cancers. A recent study from Asia indicated that elevated preoperative plasma fibrinogen might be associated with a worse outcome in patients with surgically treated localized upper tract urothelial carcinoma. We validated the prognostic impact of this potential biomarker in a European cohort of patients with localized upper tract urothelial carcinoma. MATERIALS AND METHODS: We evaluated data on 167 patients with nonmetastatic upper tract urothelial carcinoma who underwent surgery between 1990 and 2012 at a single tertiary academic center. Patients were categorized using an optimal cutoff value of preoperative plasma fibrinogen. Patient cancer specific and overall survival was assessed using the Kaplan-Meier method. Univariate and multivariate Cox regression models were performed for each end point. The influence of fibrinogen on the predictive accuracy of the multivariate model was further determined by the Harrell c-index. RESULTS: Multivariate analysis identified increased preoperative plasma fibrinogen as an independent prognostic factor for cancer specific survival (HR 3.00, 95% CI 1.32-6.80, p = 0.008) and overall survival (HR 2.48, 95% CI 1.31-4.68, p = 0.005). The estimated c-index of the multivariate model for cancer specific survival was 0.72 without fibrinogen and 0.74 when fibrinogen was added. The risk model that we developed significantly differentiated between low, intermediate and high risk groups for cancer related death (p <0.001). CONCLUSIONS: Elevated fibrinogen seems to represent a negative prognostic factor for cancer specific and overall survival in patients with upper tract urothelial carcinoma. This parameter should be considered an additional prognostic factor for upper tract urothelial carcinoma in the future.

Validation of pretreatment neutrophil-lymphocyte ratio as a prognostic factor in a European cohort of patients with upper tract urothelial carcinoma.

OBJECTIVE: To investigate the potential prognostic significance of the neutrophil-lymphocyte ratio (NLR) in a large European cohort of patients with upper urinary tract urothelial cell carcinoma (UUT-UCC). PATIENTS AND METHODS: We retrospectively evaluated data from 202 consecutive patients with non-metastatic upper urinary tract urothelial cell carcinoma (UUT-UCC), who underwent surgery between 1990 and 2012 at a single tertiary academic centre. Patients' cancer-specific survival (CSS) and overall survival (OS) were assessed using the Kaplan-Meier method. To evaluate the independent prognostic significance of the NLR, multivariate proportional Cox regression models were applied for both endpoints. RESULTS: A higher NLR was significantly associated with shorter CSS (P = 0.002, log-rank test), as well as with shorter OS (P < 0.001, log-rank test). Multivariate analysis identified a high NLR as an independent prognostic factor for patients' CSS (hazard ratio 2.72, 95% CI 1.25-5.93, P = 0.012), and OS (hazard ratio 2.48, 95% CI 1.31-4.70, P = 0.005). CONCLUSIONS: In the present cohort, patients with a high preoperative NLR had higher cancer-specific and overall mortality after radical surgery for UUT-UCC, compared with those with a low preoperative NLR. This easily identifiable laboratory measure should be considered as an additional prognostic factor in UUT-UCC in future.

Presence and extent of histological tumour necrosis is an adverse prognostic factor in papillary type 1 but not in papillary type 2 renal cell carcinoma.

AIMS: To date, only limited information is available on the prognostic significance of the presence and extent of histological tumour necrosis with regard to papillary renal cell carcinoma (RCC) types 1 and 2 subclassification. Thus, the aim of this study was to evaluate the prognostic impact of these pathological features on the clinical outcome in papillary subtypes. METHODS AND RESULTS: The influence of histological tumour necrosis on the clinical outcome in 177 patients with papillary RCC was evaluated. For papillary subtype 1, the presence of histological tumour necrosis was an independent negative prognostic factor for disease-free survival (P = 0.039), and a greater extent of necrosis (>20%) was significantly associated with both poor disease-free and overall survival (P = 0.033 and P = 0.041, respectively). Regarding papillary subtype 2, neither the presence nor extent of histological tumour necrosis was a statistically significant negative prognostic factor. CONCLUSION: Our findings suggest that the presence and extent of histological tumour necrosis are independent prognosticators in papillary RCC subtype 1, but not in papillary subtype 2. Thus, previously reported conflicting data regarding the prognostic impact of tumour necrosis in papillary RCC might be explained, in part, by heterogeneous subtypes.

Comparison of the 2002 and 2010 TNM classification systems regarding outcome prediction in clear cell and papillary renal cell carcinoma.

AIMS: A novel version of the tumour-node-metastasis (TNM) classification system for renal cell carcinoma (RCC) was introduced in 2010, although the prognostic significance with regard to different histological subtypes has not been explored. Therefore, the aim of our study was to compare the predictive ability of the 2002 and 2010 versions of the TNM classification system for clear cell and papillary RCC. METHODS AND RESULTS: Data from 2263 consecutive clear cell and 309 papillary RCC patients, operated at a single tertiary academic centre, were evaluated. According to TNM 2010, statistically significant differences for cancer-specific survival (CSS) were observed for pT1a versus pT1b (P < 0.001) and pT3a versus pT3b (P < 0.004) in clear cell RCC; and pT1b versus pT2a (P = 0.002) and pT3b versus pT3c (P = 0.046) in papillary RCC. The c-index for CSS in clear cell RCC was 0.74 and 0.73, and in papillary RCC 0.79 and 0.78, for the 2002 and 2010 versions of the TNM classification system, respectively. CONCLUSIONS: According to our data, the predictive ability of the 2010 version of the TNM classification system regarding CSS is not superior to the 2002 version, either in clear cell or in papillary RCC.

Tumour-associated macrophages might represent a favourable prognostic indicator in patients with papillary renal cell carcinoma.

AIMS: Tumour-associated macrophages (TAM) have been reported to be regulators of progression in various human cancers. We evaluated the prognostic relevance of TAM in a large series of patients with papillary renal cell carcinoma (PRCC). METHODS AND RESULTS: The impact of TAM on cancer-specific survival (CSS) in 177 patients with PRCC was assessed using the Kaplan-Meier method and log-rank test. A multivariate Cox regression analysis was performed with respect to CSS. The presence of TAM was noted in 112 of 177 (63%) tumours and was associated statistically significantly with favourable pathological parameters, including low pathological T stage, node-negative tumours, low tumour grade, absence of vascular invasion and papillary subtype (all P < 0.05), respectively. Five-year CSS probabilities for patients with TAM-positive tumours were 93.5%, compared with 72.5% in patients with TAM-negative tumours, respectively (P < 0.001). Multivariate analysis revealed node-positive tumours, distant metastases and UICC stage (I versus II-IV) as independent predictors of death from PRCC, whereas the presence of TAM was associated independently with favourable outcome (hazard ratio = 0.45, 95% confidence interval 0.24-0.84, P = 0.012). CONCLUSIONS: The presence of TAM was shown independently to reduce the risk of death from cancer by 55%. The presence of TAM should therefore become part of routine pathology reporting in PRCC.

Predictive ability of the 2002 and 2010 versions of the Tumour-Node-Metastasis classification system regarding metastasis-free, cancer-specific and overall survival in a European renal cell carcinoma single-centre series.

OBJECTIVE: To compare the predictive ability of the Tumour-Node-Metastasis (TNM) classification systems for renal cell carcinoma (RCC) using three different endpoints: metastasis-free (MFS); overall (OS); and cancer-specific survival (CSS). PATIENTS AND METHODS: Data from 2739 consecutive patients with RCC, who underwent surgery at a single academic centre, were evaluated using multivariate Cox proportional models, Harrell's concordance (c)-index and by applying decision curve analysis (DCA) with regard to MFS, OS and CSS. RESULTS: According to TNM 2010, significant differences for MFS were observed for pT1a vs pT1b, pT1b vs pT2a, pT3a vs pT3b and pT3b vs pT3c stages, respectively (all P < 0.05). With regard to OS, significant differences could be observed in pT1a vs pT1b and pT3a vs pT3b stages, respectively (all P < 0.05). The c-index for CSS, OS and MFS was slightly higher for the 2002 than for the 2010 version of the TNM classification system. Non-inferiority of the 2002 TNM system is supported by the results of the DCA. CONCLUSION: According to our data, the predictive ability of the 2010 version of the TNM classification system regarding three different clinical endpoints is not superior to the 2002 version of this staging system.