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PurposeWe hypothesized that two-tier re-classification of the “M” (metastasis) domain of the Tumor-Node-Metastasis (TNM) staging of Renal Cell Carcinoma (RCC) may improve staging accuracy than the current monolithic classification, as advancements in the understanding of tumor biology have led to increased recognition of the heterogeneous potential of metastatic RCC (mRCC).MethodsMulticenter retrospective analysis of patients from the REMARCC (REgistry of MetAstatic RCC) database. Patients were stratified by number of metastases into two groups, M1 (≤3, “Oligometastatic”) and M2 (>3, “Polymetastatic”). Primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival (CSS). Cox-regression and Kaplan-Meier (KMA) analysis were utilized for outcomes, and receiver operating characteristic analysis (ROC) was utilized to assess diagnostic accuracy compared to current “M” staging.Results429 patients were stratified into proposed M1 and M2 groups (M1 = 286/M2 = 143; median follow-up 19.2 months). Cox-regression revealed M2 classification as an independent risk factor for worsened all-cause mortality (HR=1.67, p=0.001) and cancer-specific mortality (HR=1.74, pConclusionSubclassification of Stage “M” domain of mRCC into two clinical substage categories based on metastatic burden corresponds to distinctive tumor groups whose oncological potential varies significantly and result in improved predictive capability compared to current staging.

BACKGROUND: Selection of patients for upfront cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) has to be improved. OBJECTIVE: To evaluate a new scoring system for the prediction of overall mortality (OM) in mRCC patients undergoing CN. DESIGN, SETTING, AND PARTICIPANTS: We identified a total of 519 patients with synchronous mRCC undergoing CN between 2005 and 2019 from a multi-institutional registry (Registry for Metastatic RCC [REMARCC]). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cox proportional hazard regression was used to test the main predictors of OM. Restricted mean survival time was estimated as a measure of the average overall survival time up to 36 mo of follow-up. The concordance index (C-index) was used to determine the model's discrimination. Decision curve analyses were used to compare the net benefit from the REMARCC model with International mRCC Database Consortium (IMDC) or Memorial Sloan Kettering Cancer Center (MSKCC) risk scores. RESULTS AND LIMITATIONS: The median follow-up period was 18 mo (interquartile range: 5.9-39.7). Our models showed lower mortality rates in obese patients (p = 0.007). Higher OM rates were recorded in those with bone (p = 0.010), liver (p = 0.002), and lung metastases (p < 0.001). Those with poor performance status (

INTRODUCTION AND OBJECTIVES: The role of cytoreductive nephrectomy (CN) in the setting of metastatic renal cell carcinoma (mRCC) is still object of great debate within the Urology community. In this regard, assessing the harms of CN is key to select patients most likely to benefit from this procedure. The aim of the study was to evaluate potential predictors of major complications (MC) after CN in a multicentre international cohort of patients with mRCC. METHODS: Data from patients with mRCC undergoing CN at 11 centers included in the REgistry of MetAstatic RCC (REMARCC) from January 2014 to December 2017 were retrospectively collected and analyzed. Patients with complete data on comorbidity profiles, intraoperative outcomes and perioperative complications formed the analytic cohort. Postoperative complications were assessed and graded using the modified Clavien-Dindo scale. MCs were defined as Clavien-Dindo grade 3 or more. Multivariable logistic regression analysiswas used to assess potential clinical predictors of 30-day readmission. RESULTS: Overall, 374 patients were included in the study. Twenty-three patients (6.1%) experienced MCs. Patient age, sex, BMI, Charlson comorbidity index, ECOG performance status, baseline Hb levels, estimated glomerular filtration rate, cT and cN status, as well as location of metastatic lesions, were comparable among patients who did and did not experience MCs. Conversely, median tumor size was significantly higher in patients experiencing MCs (11.0 vs 8.5 cm, p=0.002). Surgical approach was significantly different in the two study groups (87.0% of patients who experienced MCs were treated with open CN as compared to 65.4% of patients who did not; p=0.034). Performance of LDN was comparable among the study groups; on the contrary, removal of adjacent organs (43.5 % vs 23.4%, p=0.03), renal vein/vena cava thrombectomy (43.5% vs 17.4%, p=0.002) and metastasectomy at the time of CN (21.7% vs 7.1%, p=0.012) were significantly higher in patients who experienced MCs. Rate of hospital readmission within 30 days after surgery was significantly higher in patients who experienced MCs (11.1% vs 6.7%, p