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• T1a RCC treated with surgical resection had a recurrence rate of 5.4%. • The most common sites of recurrence were lungs, loco-regional, and bone. • Histology and grade were predictors for recurrence and cancer specific survival. Stage migration in renal cell carcinoma (RCC) has led to an increasing proportion of diagnosed small renal masses. Emerging knowledge regarding heterogeneity of RCC histologies and consequent impact on prognosis led us to further explore outcomes and predictive factors in surgically-treated T1a RCC. The INMARC database was queried for T1aN0M0 RCC. Patients were stratified into groups based on recurrence. Primary outcome was overall survival (OS). Multivariable analyses (MVA) were performed for factors associated with recurrence, cancer-specific (CSM), and all-cause mortality (ACM). Kaplan-Meier analyses (KMA) assessed survival by histology and grade. Subset analysis for time to recurrence was conducted for grade and histologic groups and compared with recent AUA follow-up guidelines [low-risk (AUA-LR), intermediate-risk (AUA-IR), high-risk (AUA-HR), and very-high risk (AUA-VHR) groups]. We analyzed 1,878 patients (median follow-up 35.2 months); 101 (5.4%) developed recurrence. MVA for recurrence demonstrated increasing age (P = 0.026), male sex (P = 0.043), diabetes (P = 0.007), high/unclassified grade (P < 0.001–0.007), and variant histology (P = 0.017) as independent risk factors for increased risk, while papillary (P = 0.016) and chromophobe (P = 0.049) were associated with decreased risk. MVA identified high/unclassified grade (P = 0.003–0.004) and pT3a upstaging (P = 0.043) as predictive factors for worsened risk of CSM while papillary (P = 0.034) was associated with improved risk. MVA for ACM demonstrated increasing age (P < 0.001), non-white (P < 0.001), high-grade (P = 0.022), variant histology (P = 0.049), recurrence (P = 0.004), and eGFR<45 at last follow-up (P < 0.001) to be independent risk factors. KMA comparing clear cell, chromophobe, papillary, and variant RCC revealed significant differences for 5-year CSS (P = 0.018) and RFS (P < 0.001), but not OS (P = 0.34). Median time to recurrence was 23.8 months for low-grade (AUA-LR), 17.3 months for high-grade (AUA-IR), 18 months for pT3a upstaging (AUA-HR), and 12 months for variant histology (AUA-VHR; P < 0.001). We noted differential outcomes in T1a RCC based on histology and grade for recurrence and CSM, while renal functional decline in addition to pathological factors and recurrence were predictive for ACM. Our findings support recently promulgated AUA follow-up guidelines for low-grade and variant histology pT1a RCC, but call for consolidation of follow-up protocols for high-grade pT1a and pT3a upstaged patients, with intensification of frequency of imaging follow-up in pT1a high-grade RCC. [ABSTRACT FROM AUTHOR]

The concept of "trifecta" since its first description has become a convenient tool to assess perioperative outcomes after partial nephrectomy (PN) for renal cell carcinoma (RCC). Emerging studies have demonstrated a positive association between trifecta achievement and improved survival and functional outcomes after PN. Recently, preoperative C-reactive protein (CRP) has been advocated as a useful tool to predict oncological outcome and renal functional decline. Herein we sought to integrate preoperative CRP into trifecta criteria to increase its prognostic capability. We examined our prospective database of patients with localized RCC (cT1-T3) who underwent PN. Trifecta was defined as negative surgical margins, no major postoperative complications of Clavien Dindo grade ≥3, and perioperative eGFR decrease of <30%. The primary outcome was all-cause mortality (ACM), and the secondary outcome was de novo eGFR of <45mL/min/1.73m2 (CKD-S3b). We performed multivariate analysis (MVA) using Cox regression to analyze the association between preoperative CRP and trifecta for ACM. Cut-point analysis using the concordance probability method identified CRP thresholds for low (LCRP) and high (HCRP) levels. Kaplan-Meier analysis (KMA) evaluated the overall survival (OS) and CKD-S3b progression-free survival, stratifying patients based on trifecta achievement and preoperative CRP levels. We proposed a new trifecta stratification based on the survival distributions. The Aikaike Information Criterion (AIC) was used to assess the performance of the proposed classification. 456 patients over a 34-months follow-up period were analyzed, with 316 (67.9%) achieving trifecta. MVA revealed CRP (HR;1.01,;p=0.007) as associated with higher ACM risk.;Trifecta was associated with reduced risk (HR 0.38,;p=0.004). Cut-point analysis established HCRP as ≥5 mg/L. KMA demonstrated trends in the trifecta group with 5-year OS rates of 95.6% for LCRP and 90.1% for HCRP (p=0.13). In the non-trifecta group, rates were 91.3% for LCRP and 59.7% for HCRP (p<0.001). 5-year CKD-S3b-free survival rates in the trifecta group were 83.9% (LCRP) and 80.9% (HCRP,;p=0.80), whereas rates in the non-trifecta group were 91.5% vs. 63.2%, respectively (p<0.001). Proposed risk stratification system is low (trifecta+LCRP), intermediate (trifecta+HCRP; no-trifecta+LCRP), and high (no-trifecta+HCRP). Proposed stratification;demonstrated lower AIC, translating to superior performance, in predicting ACM and CKD-S3b compared to trifecta (369.921 vs. 381.272; 661.783 vs.671.321, respectively). Our findings suggest that non-trifecta patients with low preoperative CRP demonstrated similar outcomes to patients who achieved trifecta. Together these findings suggest that preoperative CRP could identify a subgroup of patients at risk for adverse outcomes. Further investigation is warranted. [ABSTRACT FROM AUTHOR]

Partial nephrectomy (PN) has emerged as the reference standard management of localized renal masses, yet the use of PN in T3a renal cell carcinoma (RCC) is controversial, due to concerns about potential of increased procedure-related complications and oncological risk for T3a renal masses. Herein we sought to evaluate outcomes of patients treated with partial and radical nephrectomy (RN) in pT3aN0M0 RCC utilizing a propensity score match model. We conducted a multi-institutional retrospective analysis of pT3aN0M0 RCC patients who underwent PN or RN.;Type of surgery performed was made by individual surgeons in the context of shared decision making. Patients with clinical metastasis at time of surgery were excluded. A propensity score match (PSM) in a 1:1 ratio was conducted, within a caliper width of 0.1, using age at surgery, sex, body mass index (BMI), tumor histology, tumor size, cT stage, presence of positive surgical margin (SM), and tumor necrosis. Primary outcome was all-cause mortality/overall survival (ACM/OS), and secondary outcomes were cancer-specific mortality/ cancer-specific survival (CSM/CSS), recurrence/progression free survival (PFS) and new onset de novo;eGFR<45mL/min/1.73m2;(CKD-S3b). Kaplan Meier analysis (KMA) and multivariable analysis (MVA) via Cox regression were fitted to;delineate survival;outcomes and their predictors.;Multivariable logistic regression (MLR) was fitted to elucidate predictors of CKD-S3b at last follow up. After PSM 345 patients, were matched to the RN [n=161 (46.6%)] and the PN [n=184 (53.3%)] group; median follow up time 36 (IQR 14-70.5) months. MVA revealed,;age [hazard ratio (HR)1.03, p=0.022],;tumor necrosis (HR 3.79, p<0.001), SM (HR 2.97, p=0.015),;cT3 vs. cT1-T2;(HR 2.32, p=0.048) and intraoperative transfusion (HR 2.35, p=0.013) associated with ACM, while RN was not (p=0.1). MVA for CSM revealed,;cT3 vs. cT1-T2 (HR 3.80, p=0.025), and SM (HR 4.49, p=0.027) associated with CSM, while RN was not (p=0.1). MVA for recurrence revealed, SM (HR 2.59, p=0.015) as independent risk factor, while RN was not (p=0.4). KMA comparing PN vs. RN revealed 5-year OS of 87.5% vs. 81.3% (p=0.2,;Figure); 5-year CSS of 96.1% vs. 89.9% (p=0.09,;Figure) and 5-year PFS of 76.4% vs. 73.3% (p=0.9,;Figure). MLR revealed RN (OR 2.71, p=0.003) associated with development of new onset CKD-S3b. In a PSM model of pT3aN0M0, PN exhibited oncological equipoise while reducing risk of development of eGFR<45mL/min/1.73m.2;;PN may be considered as an alternative to RN in T3a RCC when prioritization of functional preservation is indicated. Further investigation is requisite. [ABSTRACT FROM AUTHOR]

The role of lymphadenectomy in localized renal cell carcinoma (RCC) remains controversial. We sought to develop a preoperative nomogram called NODESAFE (NODE SAFEty) to predict;nodal tropism (NT) defined as nodes invasion at the histological report (NI) or nodes metastasis (NM) at follow up. We conducted a retrospective analysis of the INMARC database of RCC patients who underwent primary surgical resection. Patients with clinical metastasis at presentation were excluded. NM was defined as development of a new adenopathy greater than 10mm at the CT scan during follow-up. NODESAFE model was constructed through a stepwise multivariable logistic regression (MLR) model. Accuracy was tested with receiver operator characteristic estimated area under the curve (AUC). Internal validation was performed through cross validation analysis. 2,297 patients met inclusion criteria. On MLR: cN (OR 5.90, p<0.001), tumor size≥6cm (OR 3.04, p<0.001), c-reactive protein≥8.5mg/L (OR 1.98, p=0.011), neutrophile-lymphocyte ratio≥2.5 (OR 1.74, p=0.034), low enhancement in CT imaging (OR 2.05, p=0.009), hypertension (OR 2.78, p<0.001) and Charlson Comorbidity Index≥6 (OR 2.57, p=0.001) were independent predictors for NT. NODESAFE model was constructed from these variables;(Figure 1).;AUC was 0.87 (Figure 2) and 0.84 after cross validation analysis. NODESAFE risk calculator is available at http://nodesafe.pythonanywhere.com/. 3.9% threshold probabilities displayed 73.5% sensitivity, 84.5% specificity and 98.8% negative predictive value. Combining clinical features, serum biomarkers and radiographic findings, we developed a model capable of predicting with accuracy nodes tropism. NODESAFE may refine clinical decision making with respect to the performance of lymphadenectomy at the time of surgery, post-surgical surveillance, and spur consideration for adjuvant therapy. [ABSTRACT FROM AUTHOR]

• The "obesity paradox" is not an observable phenomenon across different renal cortical tumors. • Obesity is not associated with improved survival and recurrence in nonclear cell renal cell carcinoma (RCC) and in nonmetastatic clear cell RCC while metastatic clear cell RCC patients with obesity had improved oncological outcomes, due to an increased metabolic reserve and associated heightened inflammatory state which could amplify treatment responses. To investigate impact of body mass index (BMI) on survival across different histologies and stages of renal cell carcinoma (RCC). We conducted a retrospective multicenter analysis of clear cell (ccRCC) and non-ccRCC. Obesity was defined according to the WHO criteria (non-Asian BMI >30 Kg/m2, Asian BMI >27.5 Kg/m2). Multivariable analysis (MVA) via Cox regression model was conducted for all-cause (ACM), cancer-specific mortality (CSM) and recurrence. A total of 3,880 patients with a median follow-up of 31 (IQR 9–64) months were analyzed. Overall, 1,373 (35.3%) were obese; 2,895 (74.6%) were ccRCC and 985 (25.3%) were non-ccRCC (chRCC 246 [24.9%], pRCC 469 [47.6%] and vhRCC 270 [27.4%]). MVA in ccRCC revealed obesity associated with decreased risk of ACM, CSM and recurrence (hazard ratio [HR] 0.80, P = 0.044; HR 0.71, P = 0.039; HR 0.73, P = 0.012, respectively), while in non-ccRCC was not associated with decreased risk of ACM, CSM, and recurrence (P = 0.84, P = 0.53, P = 0.84, respectively). Subset analysis in stage IV ccRCC demonstrated obesity as associated with a decreased risk of ACM, CSM, and recurrence (HR 0.68, P = 0.04; HR 0.59, P = 0.01; HR 0.59, P = 0.01, respectively), while in stage I–III ccRCC was not (P = 0.21; P = 0.30; P = 0.19, respectively). Our findings refute a broad "obesity paradox" for RCC. Obesity was not associated with improved survival in non-ccRCC and in nonmetastatic ccRCC, while metastatic ccRCC patients with obesity had improved survival outcomes. [ABSTRACT FROM AUTHOR]

C-reactive protein (CRP) is an inflammatory marker whose elevation has been associated with worsened outcomes in renal cell carcinoma (RCC). Most studies have focused on pre-treatment values however, and there is a dearth of literature on impact of CRP dynamics. We sought to evaluate the impact of C-reactive protein dynamics (CRP) in Renal Cell Carcinoma (RCC) as biomarker for recurrence. We conducted a two center retrospective analysis of patients undergoing surgery for RCC.;;In all patients presenting for surgery, CRP was collected pre-operatively and postoperatively at 3 months, 6 months, then annually thereafter. The most recent CRP before recurrence was used to calculate delta CRP (postoperative– preoperative-CRP). Cut-point analysis employing concordance probability method was performed to determine the thresholds for preoperative CRP and delta CRP. Based on the ROC analysis, patients were stratified by preoperative CRP [low ≤1.5 mg/L (LCRP) vs. high >1.5mg/L (HCRP)], and by delta-CRP ≤1.5 mg/L (low-delta) vs. >1.5mg/L high-delta. Primary outcome was predictors of recurrence and secondary outcome was overall survival (OS). Multivariable analysis (MVA) via Cox regression was fitted for predictor of recurrence and all-cause mortality (ACM). Kaplan-Meier analysis (KMA) was assessed to compare this stratification for progression free (PFS) and overall survival (OS). 1932 patients were analyzed [LCRP/low-delta 773 (40.1%), LCRP/high-delta 292 (15.1%), HCRP/low-delta 689 (35.6%), HCRP/high-delta 178 (9.2%)]. MVA showed that LCRP/high-delta (HR 2.02, p<0.001), HCRP/low-delta (HR 1.7, p<0.001), and HCRP/high-delta (HR 2.28, p<0.001) were independent predictors associated with increased risk of recurrence. MVA for ACM demonstrated HCRP/low-delta (HR 2.64, p<0.001) and HCRP/high-delta (HR 4.89, p<0.001), associated with increased risk of mortality while LCRP/low-delta was not (p=0.32). 5 years PFS (Figure 1) was 91.1% for LCRP/low-delta, 86.5% for LCRP/high-delta, 80.7% for HCRP/low-delta and 73.% for HCRP/high-delta (p<0.001). 5-year OS (Figure 2) was 96.1% for LCRP/low-delta, 94.9% for LCRP/high-delta, 85.7% for HCRP/low-delta and 76.8% for HCRP/high-delta (p<0.001) Our findings suggest that CRP-kinetics is an independent predictor of worsened survival outcomes and recurrence, as such might may thus identify a subgroup of patients in which closer follow up or consideration for adjuvant therapy may be of benefit. Further investigation is requisite. [ABSTRACT FROM AUTHOR]

To create and;validate;U.N.I.K.;(Urologic Non-neoplastic Investigation of Kidneys), a model capable of predicting the probability of benign lesion at final histological report in patients suspected of renal cell carcinoma (RCC). We quired the INMARC database for cT1/2 renal neoplasms who underwent surgery. Primary objective was the development of a model (U.N.I.K.) capable of predicting benign renal lesions (angiomyolipoma, oncocytoma and other benign neoplasia) through a stepwise multivariable logistic regression (MLR) model. Secondary outcomes include internal validation through cross validation, decision curve analysis (DCA) and calibration plot. Overall, 3,093were analyzed [2,876 RCC (92.9%) vs. 217 benign histology (7.1%)]. On MLR female sex (OR 2.36, p<0.001), diabetes mellitus (OR 2.90, p<0.001), tumor size<3cm (OR 3.56, p<0.001), preoperative-CRP<1mg/L (OR 1.77, p<0.001), preoperative-eGFR>100 mL/min/1.73m2;(OR 3.01, p<0.001), preoperative-platelet counts≥255×109/L (OR 1.48, p=0.017), preoperative calcium≥9.34mg/dL (OR 2.39, p<0.001), Charlson Comorbidity Index<3 (OR 1.78, p=0.005) and cystic lesion (OR 17.32, p<0.001) as independent predictors of benign lesion. U.N.I.K. nomogram was constructed from these predictors;(Figure 1a).;AUC (Figure 1b) of the model was 0.85, and 0.81;;after cross validation analysis. DCA and calibration plot are depicted in;Figure 2a-2b. 7% threshold probability showed 74.7% sensitivity, 80.1% specificity and 97.7% negative predictive value. Combining clinical features, serum biomarkers and radiographic findings, we have developed a point of care model (U.N.I.K.) capable of predicting, with significant accuracy, benign tumor in patients with cortical renal neoplasms being considered for surgical resection. U.N.I.K. nomogram may refine clinical decision making with respect to identification of patients with increased likelihood of benign tumor histology and reduce burden of surgical overtreatment. External validation is requisite. [ABSTRACT FROM AUTHOR]

Renal Cell Carcinoma (RCC) is a highly lethal neoplasm that accounts for 3% of tumors globally and is the deadliest of common urologic cancers. Current literature highlights tumor grade and pathological stage as the predominant prognostic factors for oncological outcome according to the American Joint Committee on Cancer (AJCC) classification. Although attempts have been made to further stratify survival outcomes using clinical and laboratory data, the TNM/AJCC staging, gold standard for RCC, has yet to incorporate these prognostic indices. Nevertheless, there is growing evidence supporting the value of C-reactive protein (CRP) as a predictor for oncological outcomes in RCC. We hypothesized that integrating the AJCC stage classification system with preoperative CRP will allow for more accurate staging, outcome detection, and clinical decision making, with respect to RCC;disease. We queried the International Marker Consortium for Renal cancer (INMARC) registry for patients older than 18 affected by RCC.;Multivariable analysis (MVA) via Cox regression was employed to test the efficacy of CRP predicting all-cause mortality (ACM). Cut-point analysis employing concordance probability method was performed to identify CRP thresholds for defining low (LCRP) and high CRP (HCRP). We sorted the cohort based on the results of the cut-point analysis (LCRP <5 mg/L; HCRP≥5 mg/L) for survival assessment. Kaplan-Meier analyses (KMA) were fitted to elucidate survival estimates stratifying for AJCC and CRP level. Proposed classification was based on the results of the KMA distributions for overall survival (OS). Performance of the proposed model was assessed with Akaike information criterion (AIC), and receiver operating characteristic curve (ROC) analysis using estimated area under the curve (AUC) for ACM and cancer specific mortality (CSM). We identified 3,432 patients.;MVA showed HCRP as an independent predictor associated with ACM (HR;2.50, p<0.001). Comparing stage I/LCRP vs. stage I/HCRP 5-years KMA for OS was 93.9% vs. 83.6% (p<0.001); for;stage II/LCRP vs. stage II/HCRP;was 94.2% vs 76.6% (p<0.001). Comparing stage I/HCRP vs. stage III/low-CRP 5-years OS was 83.6% vs. 84.6% (p=0.8); for;stage II/HCRP vs IV/LCRP was 76.6% vs 77.2%. (p=0.6); for stage IV/LCRP vs. stage III/HCRP was 77.2% vs. 60.5% (p=0.002). Proposed classification is depicted in;Figure 1.;AUC for proposed classification showed improved performance relative to AJCC in predicting ACM and CSM (0.72 vs 0.67, p<0.001; 0.80 vs 0.78, p<0.001, respectively,;Figure 2). On MVA proposed classification exhibited lower AIC compared to AJCC which is indicative of a superior model (ACM: 9209.661 vs. 9398.321; CSM: 4514.647 vs. 4628.922). We present a pragmatic and easy to use stratification system that exhibits increased prognostic performance, as compared to the current AJCC staging system, by utilizing CRP. Our analyses, reveals that tumors formally staged as AJCC stage II with high CRP,;exhibit long term detrimental characteristics;equivalent to AJCC stage IV with low CRP.;Our results call for a reconsideration of the current anatomopathological paradigm of RCC staging and to reflect a more nuanced perspective that includes biological features as well. Our proposal classification, which serves as a trait d'union between biological and staging data, could potentially identify patients with worse prognostic outcomes in a cost-effective fashion. Further investigation is requisite. [ABSTRACT FROM AUTHOR]

While hypertension (HTN) is an important co-morbidity, it's not included in the Charlson Comorbidity Index (CCI), which assess impact of comorbidities on survival, and;impact of HTN on oncologic outcomes in Renal Cell Carcinoma (RCC) is uncertain. We sought to analyze the impact of HTN on RCC outcomes in a contemporary cohort of patients who underwent surgery. We performed a multi-center retrospective analysis of patients who underwent radical (RN) or partial nephrectomy (PN) for RCC utilizing the INMARC;database. Primary outcome was;all-cause mortality (ACM); secondary outcomes included cancer-specific mortality (CSM), and recurrence. Multivariable analysis (MVA) via cox regression were fitted to elucidate predictors for outcomes, and Kaplan-Meier analyses (KMA), were performed to analyze overall survival (OS), cancer-specific survival (CSS) and recurrence-free survival (RFS). We analyzed 4859 patients (2,018 with HTN/2841 without HTN); median follow-up 55.5 months. MVA revealed age (HR 1.01, p<0.001), HTN (HR 1.44, p<0.001), CCI (HR 1.04, p<0.001), tumor size (HR 1.04, p<0.001), RN (HR 1.36, p<0.001), stage IV (HR 1.86, p=0.003), and tumor necrosis (HR 1.23, p=0.005), as associated with increased risk of ACM.;MVA for CSM revealed HTN (HR 1.42, p=0.001), CCI (HR 1.07, p<0.001), tumor size (HR 1.04, p=0.003), and stage IV (HR 2.71, p<0.001) as associated with increased risk of CSM. MVA for recurrence revealed HTN (HR 1.36, p<0.001), tumor size (HR 1.07, p<0.001), and stage IV (HR 3.25, p<0.001), as;;associated with recurrence. KMA comparing non HTN vs. HTN revealed 5-year OS of 88.2% vs. 72.2%, 5-year CSS of 94% vs. 83.8%, and 5-year RFS of 93.1% vs. 82.8% (all p<0.001,;Figure). Hypertension is an independent risk factor for worsened oncologic and survival outcomes in patients undergoing surgical treatment for RCC. Further investigation is warranted to confirm these findings and elucidate mechanisms of action and explore strategies to improve outcomes with improved control of hypertension. [ABSTRACT FROM AUTHOR]