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Background: The aim of this study is to evaluate the perioperative and long-term functional outcomes of laparoscopic (LPN) and robot-assisted partial nephrectomy (RAPN) in comparison to laparoscopic radical nephrectomy (LRN) in obese patients diagnosed with renal cell carcinoma., Methods: Clinical data of 4325 consecutive patients from The Italian REgistry of COnservative and Radical Surgery for cortical renal tumor Disease (RECORD 2 Project) were gathered. Only patients treated with transperitoneal LPN, RAPN, or LRN with Body Mass Index (BMI) ≥30 kg/m 2 , clinical T1 renal tumor and preoperative estimated glomerular filtration rate (eGFR) ≥60 mL/min, were included. Perioperative, and long-term functional outcomes were examined., Results: Overall, 388 patients were included, of these 123 (31.7%), 120 (30.9%) and 145 (37.4%) patients were treated with LRN, LPN, and RAPN, respectively. No significant difference was observed in preoperative characteristics. Overall, intra and postoperative complication rates were comparable among the groups. The LRN group had a significantly increased occurrence of acute kidney injury (AKI) compared to LPN and RAPN (40.6% vs. 15.3% vs. 7.6%, P=0.001). Laparoscopic RN showed a statistically significant higher renal function decline at 60-month follow-up assessment compared to LPN and RAPN. A significant renal function loss was recorded in 30.1% of patients treated with LRN compared to 16.7% and 10.3% of patients treated with LPN and RAPN (P=0.01)., Conclusions: In obese patients, both LPN and RAPN showcased comparable complication rates and higher renal function preservation than LRN. These findings highlighted the potential benefits of minimally invasive PN over radical surgery in the context of obese individuals.

Background: It is unknown whether previously reported other-cause mortality (OCM) advantage of partial cytoreductive nephrectomy (PCN) vs. radical cytoreductive nephrectomy (RCN) still applies to contemporary clear cell metastatic renal cell carcinoma (ccmRCC) patients., Materials and Methods: We relied on the Surveillance, Epidemiology and End Results (SEER) database (2004-2019) to identify ccmRCC patients treated with PCN and RCN. Temporal trends of PCN rates within the SEER database were tabulated. After propensity score matching (PSM), cumulative incidence plots depicted 5-year OCM and cancer-specific mortality (CSM) of PCN and RCN patients. Multivariable Cox regression models tested for differences between PCN vs. RCN., Results: Of 5149 study patients, 237 (5%) underwent PCN vs. 4912 (95%) RCN. In the SEER database 2004 to 2019, rates of PCN in ccmRCC patients increased from 3.0% to 8.0% (estimated annual percent change [EAPC]: 3.0%; P = .04). After PSM, 5-year OCM rates were 2.4 vs. 7.5% for respectively PCN vs. RCN patients (P = .036). 5-year CSM rates were 50.8 vs. 53.6% for respectively PCN and RCN patients (P = .57). In multivariable Cox regression models, PCN was associated with lower OCM (Hazard Ratio (HR): 0.39; 95% confidence interval (CI): 0.18-0.84; P = .02) but did not affect CSM rates (HR: 0.99; 95% CI: 0.76-1.29; P = .96)., Conclusions: We confirm the existence of OCM advantage after PCN vs. RCN in contemporary ccmRCC patients., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The prognostic significance of number and location of organ-specific metastatic sites in treated metastatic clear cell renal carcinoma (ccmRCC) patients is object of debate. The current study aimed to test the association between number and location of organ-specific metastatic sites and overall survival (OS) in ccmRCC., Materials and Methods: Within Surveillance, Epidemiology and End Results database (2010-2018), all ccmRCC patients treated with cytoreductive nephrectomy and/or systemic therapy were identified. Kaplan-Meier plots and Cox regression models focused on: A). number of organ-specific metastatic sites: solitary vs. 2 vs. 3 or more; B). solitary organ-specific metastatic sites (lung vs. bone vs. liver vs. brain); C). combinations of 2 and 3 or more different organ-specific metastatic sites., Results: Of 4,527 patients (median OS: 19 months), 3,054 (67%) harbored solitary organ-specific metastatic sites (27 months) vs. 1,153 (25%) combinations of 2 different organ-specific metastatic sites (12 months) vs. 320 (8%) combinations of 3 or more different organ-specific metastatic sites (7 months). In patients with solitary organ-specific metastatic sites, bone metastases portended the longest median OS (median OS: 31 months) vs. liver metastases portended the shortest median OS (16 months). Both were independent predictors of OS (multivariable hazard ratio, bone: 0.87; liver: 1.21). Median OS was similarly poor in patients with combinations of 2 different organ-specific metastatic sites (9-13 months), regardless of their location. The same pattern applied to patients with combinations of 3 or more different organ-specific metastatic sites (6-7 months)., Conclusions: Solitary organ-specific metastatic sites portend the most favorable OS (16-31 months). Solitary bone metastases yield the longest vs. liver metastases the shortest OS. Invariably poor OS applies to combinations of 2 (9-13 months), as well as 3 or more different organ-specific metastatic sites (6-7 months), regardless of their location., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: To test for regional differences in clear cell metastatic renal cell carcinoma (ccmRCC) patients across the USA., Methods: The Surveillance, Epidemiology, and End Results (SEER) database (2000-2018) was used to tabulate patient (age at diagnosis, sex, race/ethnicity), tumor (N stage, sites of metastasis) and treatment characteristics (proportions of nephrectomy and systemic therapy), according to 12 SEER registries. Multinomial regression models, as well as multivariable Cox regression models, tested the overall mortality (OM) adjusting for those patient, tumor and treatment characteristics., Results: In 9882 ccmRCC patients, registry-specific patient counts ranged from 4025 (41%) to 189 (2%). Differences across registries existed for sex (24-36% female), race/ethnicity (1-75% non-Caucasian), N stage (N1 25-35%, NX 3-13%), proportions of nephrectomy (44-63%) and systemic therapy (41-56%). Significant inter-registry differences remained after adjustment for proportions of nephrectomy (46-63%) and systemic therapy (35-56%). Unadjusted 5-year OM ranged from 73 to 85%. In multivariable analyses, three registries exhibited significantly higher OM (SEER registry 5: hazard ratio (HR) 1.20, p = 0.0001; SEER registry 7:HR 1.15, p = 0.008M SEER registry 10: HR 1.15, p = 0.04), relative to the largest reference registry (n = 4025)., Conclusion: Important regional differences including patient, tumor and treatment characteristics exist, when ccmRCC patients included in the SEER database are studied. Even after adjustment for these characteristics, important OM differences persisted, which may require more detailed analyses to further investigate these unexpected differences., (© 2023. The Author(s).)

Background: Accurate prediction of cancer control outcomes in renal cell carcinoma (RCC) patients is important for counselling, follow-up planning, and selection of appropriate adjuvant trial designs., Objective: To develop and externally validate a novel contemporary population-based model for predicting cancer-specific mortality-free survival (CSM-FS) in surgically treated papillary RCC (papRCC) patients and to compare it with established risk categories (Leibovich 2018)., Design, Setting, and Participants: Within the Surveillance, Epidemiology, and End Results database (2004-2019), we identified surgically treated papRCC patients (n = 3978). The population was randomly divided into development (50%, n = 1989) and external validation (50%, n = 1989) cohorts. Of the external validation cohort, 97% (n = 1930) of patients were included in a head-to-head comparison of the Leibovich 2018 risk categories addressing nonmetastatic patients., Outcome Measurements and Statistical Analysis: Univariable Cox regression models tested the statistical significance in the prediction of CSM-FS. The most parsimonious model with the best validation metrics was selected as the multivariable nomogram. Accuracy, calibration, and decision curve analyses (DCAs) tested the Cox regression-based nomogram, as well as the Leibovich 2018 risk categories in the external validation cohort., Results and Limitations: Age at diagnosis, grade, T stage, N stage, and M stage qualified for inclusion in the novel nomogram. In external validation, the accuracy of the novel nomogram was 0.83 at 5 yr and 0.80 at 10 yr. In nonmetastatic patients, 5- and 10-yr accuracy of the novel nomogram was 0.77 and 0.76, respectively. Conversely, 5- and 10-yr accuracy of the Leibovich 2018 risk categories was 0.70 and 0.66, respectively. The novel nomogram exhibited smaller departures from ideal predictions in calibration plots and higher net benefit in DCAs, when it was compared with the Leibovich 2018 risk categories. Limitations include the retrospective nature of the study, absence of a central pathological review, and inclusion of only North American patients., Conclusions: The novel nomogram may represent a valuable clinical aid, when papRCC CSM-FS predictions are required., Patient Summary: We developed an accurate tool to predict death due to papillary kidney cancer in a North American population., (Copyright © 2023 European Association of Urology. All rights reserved.)

Background: It is unknown whether the survival benefit of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) applies to patients with primary tumor size ≤4 cm., Objective: To test the association between CN on overall survival (OS) of mRCC patients with primary tumor size ≤4 cm., Design, Setting, and Participants: Within the Surveillance, Epidemiology, and End Results (SEER) database (2006-2018), all mRCC patients with primary tumor size ≤4 cm were identified., Outcome Measurements and Statistical Analysis: Propensity score matching (PSM), Kaplan-Meier plots, multivariable Cox regression analyses, and 6-mo landmark analyses addressed OS according to CN status. Sensitivity analyses examined specific populations of special interest: systemic therapy exposed versus naïve, clear-cell (ccmRCC) versus non-clear-cell (non-ccmRCC) mRCC histology, historical (2006-2012) versus contemporary (2013-2018), and young (≤65 yr) versus old (>65 yr) patients., Results and Limitations: Of 814 patients, 387 (48%) underwent CN. After PSM, the median OS was 44 versus 7 mo (Δ = 37 mo; p < 0.001) in CN versus no-CN patients. CN was associated with higher OS in overall population (multivariable hazard ratio [HR]: 0.30; p < 0.001) as well as in landmark analyses (HR: 0.39; p < 0.001). In all sensitivity analyses, CN was independently associated with higher OS: systemic therapy exposed, HR: 0.38; systemic therapy naïve, HR: 0.31; ccmRCC, HR: 0.29; non-ccmRCC, HR: 0.37; historical, HR: 0.31; contemporary, HR: 0.30; young, HR: 0.23; and old, HR: 0.39 (all p < 0.001)., Conclusions: The current study validates the association between CN and higher OS in patients with primary tumor size ≤4 cm. This association is robust, controlled for immortal time bias, and valid across systemic treatment exposure, histologic subtypes, years of surgery, and patient age., Patient Summary: In the current study, we tested the association between cytoreductive nephrectomy (CN) and overall survival in patients with metastatic renal cell carcinoma and small primary tumor size. We found a strong association between CN and survival, which persists even after several significant variations in patient and tumor characteristics., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: To date, five trials testing the effect of adjuvant systemic therapy in surgically treated non-metastatic renal cell carcinoma included patients with non-clear cell histology. We tested the effect of papillary vs. chromophobe histological subtype, stage, and grade on 10-year cancer-specific survival, in patients eligible for ≥1 such trial., Methods: We identified patients meeting ASSURE, SORCE, EVEREST, PROSPER, or RAMPART trial inclusion criteria in the SEER (2000-2018) database. Kaplan-Meier analyses estimated 10-year survival rates and multivariable Cox regression models tested for the independent predictor status of histological subtype, stage, and grade., Results: We identified 5465 (68%) papillary and 2562 (32%) chromophobe renal cell carcinoma patients. Cancer-specific survival rates at 10 years were 77% in papillary vs. 90% in chromophobe. In multivariable Cox regression models applied to papillary patients, cancer-specific mortality independent predictor status was reached for T3G3-4 (HR 2.9), T4Gany (HR 3.4), TanyN1G1-2 (HR 3.1), and TanyN1G3-4 (HR 8.0, P<0.001), relative to T1/2Gany. In multivariable Cox regression models applied to chromophobe patients, mortality independent predictor status was reached for T3G3-4 (HR 3.6), T4Gany (HR 14.0), TanyN1G1-2 (HR 5.7), and TanyN1G3-4 (HR 15.0, P<0.001), relative to T1/2Gany., Conclusions: In surgically treated non-metastatic intermediate/high-risk renal cell carcinoma patients, papillary histologic subtype exhibited worse cancer-specific survival than chromophobe histologic subtype. Although stage and grade represented independent predictors in both histological subtype groups, the magnitude of their effect was invariably worse in chromophobe than in papillary patients. In consequence, papillary and chromophobe patients should be considered separate entities instead of being combined under the non-clear cell designation.

Introduction: Controlled contemporary analyses of mortality in metastatic collecting duct renal cell carcinoma (mcdRCC) are unavailable. We addressed this knowledge gap and tested rates of treatment and associated mortality in patients with mcdRCC., Patients and Methods: Within Surveillance, Epidemiology, and End Results database (2004-2018), we identified 155 mcdRCC patients. Kaplan-Meier plots and Cox proportional hazards regression models tested the effect of treatment (cytoreductive nephrectomy [CN] alone vs. systemic therapy [ST] alone vs. combination of both CN + ST) on overall mortality (OM)., Results: In the overall cohort (n = 155), 57 patients (37%) were treated with combination of both CN + ST, 46 (30%) underwent CN alone, 28 (18%) received ST alone, and 24 (15%) had none/unknown treatment. According to age categories (≤ 59 vs. 60-69 vs. ≥ 70 years), rates of combination of both CN + ST were 45% vs. 45% vs. 14%, respectively. CN alone was the most frequent type of treatment in patients aged ≥ 70 (50%). Median overall survival was 4.0 months for CN alone vs. 5.5 months for ST alone vs. 9.0 months for combination of both CN+ST. In multivariable Cox regression models, where CN alone was the referent, the use of ST alone and combination of both CN + ST were respectively associated with a HR of 0.74 (P = .3) and 0.43 (P < .001), after adjustment for all covariates., Conclusions: In mcdRCC patients, concomitant use of CN and ST results in lowest mortality, followed by ST alone, and CN alone. In consequence combination of both CN + ST should be recommended whenever applicable., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: To quantify differences in five-year overall survival (OS) between clear cell metastatic renal cell carcinoma (ccmRCC) patients and age- and sex-matched population-based controls, especially when race/ethnicity is considered., Methods: We relied on the Surveillance, Epidemiology and End Results database (2006-2016) to identify newly diagnosed (2006- 2011) ccmRCC patients of either Caucasian, Hispanic, African American, or Asian/Pacific Islander race/ethnicity. For each case, we simulated an age- and sex-matched control (Monte Carlo simulation), relying on Social Security Administration Life Tables with five-year follow-up. We compared OS between ccmRCC patients and controls. Multivariable Cox regression models tested for race/ethnicity effect on OS., Results: Of 3067 ccmRCC patients, 2167 (71%) were Caucasians vs. 488 (16%) Hispanics vs. 216 (7%) African Americans and 196 (6%) Asians/Pacific Islanders. At five years, OS difference between ccmRCC patients vs. population-based controls was greatest in African Americans (11 vs. 94%, Δ = 84%), followed by Hispanics (16 vs. 94%, Δ = 77%), Caucasians (16 vs. 89%, Δ = 73%) and Asians/Pacific Islanders (19 vs. 88%, Δ = 70%). In multivariable Cox regression models, African Americans exhibited highest Hazard Ratio for death (HR 1.3, p= 0.003)., Conclusion: Relative to Life Tables' derived age- and sex-matched controls, ccmRCC patients exhibit drastically worse OS, especially African Americans., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Collecting duct carcinoma (CDC) is a rare renal malignancy. We relied on a large population-based cohort to address epidemiology, clinical characteristics, and treatment of CDC patients. We also tested survival in the overall cohort, as well as in stage-specific fashion., Materials and Methods: Within Surveillance, Epidemiology, and End Results (2004-2018) database, we identified 399 CDC patients. Based on Kaplan-Meier plots survival estimates, conditional survival rates were derived according to disease stage. Cox regression models tested for predictors of cancer specific mortality (CSM)., Results: Overall, 273 (68.4%) patients were male, 236 (59.2%) had T3-4 stages, 148 (37.1%) had lymph node invasion, and 156 (39.1%) had distant metastases at initial diagnosis. Nephrectomy alone was commonest in stage I-II (n = 91/99, 92%) and III (n = 94/116, 81%). Combination of both nephrectomy and systemic therapy was commonest in stage IV (n = 62/172, 36%). In the overall cohort, median cancer specific survival was 18 months. Provided a disease-free interval of 24 months, five-year Kaplan-Meier estimated survival at diagnosis increased from 74.2 to 91.0% in stage I-II, from 31.1 to 65.3% in stage III, and from 6.3 to 34.1% in stage IV. In multivariable Cox regression models addressing CSM, systemic therapy (Hazard Ratio [HR]: 0.47, P = 0.020), nephrectomy (HR: 0.37, P < 0.001) and combination of both (HR: 0.28, P < 0.001) exhibited a strong protective effect., Conclusion: Despite its highly aggressive phenotype and dismal survival, CDC is sensitive to nephrectomy and/or systemic therapy. Moreover, even for advanced stage, a more favorable prognosis can be achieved in patients, who benefit of disease-free interval after diagnosis and initial treatment., Competing Interests: Conflict of interest The authors declare that there is no conflict of interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Collecting duct carcinoma (CDC) is biologically more aggressive than clear cell renal cell carcinoma (ccRCC). We tested for differences in cancer specific mortality (CSM) rates according to CDC vs. ISUP (International Society of Urological Pathology) 4 ccRCC histological subtype. We hypothesized that the survival disadvantage still applies, even after most detailed adjustments., Methods: Within Surveillance, Epidemiology, and End Results database (2004-2018), we identified 380 CDC vs. 6273 ISUP 4 ccRCC patients of all stages. Propensity score matching (age, sex, race/ethnicity, T, N, and M stages, nephrectomy, and systemic therapy status), Kaplan-Meier plots and multivariable Cox regression models were used., Results: All 380 CDC were matched (1:2) with 760 ISUP4 ccRCC patients. Prior to matching CDC patients exhibited higher rates of lymph node invasion (37.6 % vs. 14.7 %, p < 0.001), and of distant metastases (40.8 % vs. 30.4 %, p < 0.001). Systemic therapy rates were higher in CDC (29.5 % vs. 20.5 %, p < 0.001). However, nephrectomy rates were higher in ISUP4 ccRCC patients (97.5 % vs. 84.7 %, p < 0.001). After matching, in multivariable Cox regression models addressing CSM, CDC was associated with a HR of 1.5 (p < 0.001) in the overall population vs. 1.9 (p = 0.014) in stage I-II vs. 1.4 (p = 0.022) in stage III vs. 1.6 in stage IV (p < 0.001), relative to ISUP4 ccRCC., Conclusion: CDC patients exhibited 40-90 % higher CSM than their ISUP4 ccRCC counterparts in the overall analysis, as well as in stage specific analyses. The CSM disadvantage applies despite higher rates of systemic therapy in CDC patients., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Large-scale analyses addressing cancer-specific mortality (CSM) in T1a renal cell carcinoma (RCC) patients treated with local tumor destruction (LTD), relative to partial nephrectomy (PN), are scarce., Objective: To compare CSM after LTD versus PN., Design, Setting, and Participants: Within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2018), we identified patients with clinical T1a stage RCC treated with LTD or PN., Outcome Measurements and Statistical Analyses: After 1:1 ratio propensity score matching (PSM) between patients treated with LTD versus PN, competing risks regression (CRR) models addressed CSM, after adjustment for other-cause mortality (OCM) and other covariates (age, tumor size, tumor grade, and histological subtype)., Results and Limitations: Relative to the 35 984 PN patients, 5936 LTD patients were older and more frequently harbored unknown RCC histological subtype or unknown grade. After 1:1 PSM that resulted in 5352 LTD versus 5352 PN patients, the 10-yr CSM rate was 8.7% versus 5.5%. In multivariable CRR models, LTD was associated with higher CSM, relative to PN (hazard ratio [HR]: 1.58, p < 0.001). Subgroup analyses revealed invariably higher CSM after LTD versus PN in patients with tumor size ≤3 cm (10-yr CSM 7.2% vs 5.3%, multivariable HR: 1.47, p < 0.001) and in patients with tumor size 3.1-4 cm (10-yr CSM 11.4% vs 6.1%, multivariable HR: 1.72, p < 0.001). Lack of information regarding earlier cancer controls, retreatment, tumor location within the kidney, and type of surgery represented limitations., Conclusions: In T1a RCC patients, LTD is invariably associated with higher CSM relative to PN, even after adjustment for OCM and all available patient and tumor characteristics, and regardless of tumor size considerations. However, the magnitude of CSM disadvantage was more pronounced in LTD patients with tumor size 3.1-4 cm than in those with tumor size ≤3 cm., Patient Summary: In patients with small renal masses, we observed higher cancer-specific death rates for local tumor destruction (LTD) than for partial nephrectomy. The LTD disadvantage was more pronounced for patients with tumor size 3.1-4 cm, but was also present in those with tumor size ≤3 cm., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: Guidelines suggest less favorable cancer control outcomes for local tumor destruction in T1a renal cell carcinoma patients with tumor size 3.1-4 cm. We compared cancer-specific mortality between cryoablation vs heat-based thermal ablation in patients with tumor size 3.1-4 cm, as well as in patients with tumor size ≤3 cm., Materials and Methods: Within the Surveillance, Epidemiology, and End Results database (2004-2018), we identified patients with clinical T1a stage renal cell carcinoma treated with cryoablation or heat-based thermal ablation. After up to 2:1 ratio propensity score matching between patients treated with cryoablation vs heat-based thermal ablation, we addressed cancer-specific mortality relying on competing risks regression models, adjusted for other-cause mortality and other covariates (age, tumor size, tumor grade, and histological subtype)., Results: Of 1,468 assessable patients with tumor size 3.1-4 cm, 1,080 vs 388 were treated with cryoablation vs heat-based thermal ablation, respectively. After up to 2:1 propensity score matching that resulted in 757 cryoablations vs 388 heat-based thermal ablations, in multivariable competing risks regression models, heat-based thermal ablation was associated with higher cancer-specific mortality (HR:2.02, P < . 001), relative to cryoablation. Of 4,468 assessable patients with tumor size ≤3 cm, 3,354 vs 1,114 were treated with cryoablation vs heat-based thermal ablation, respectively. After up to 2:1 propensity score matching that resulted in 2,217 cryoablations vs 1,114 heat-based thermal ablations, in multivariable competing risks regression models, heat-based thermal ablation was not associated with higher cancer-specific mortality (HR:1.13, P = . 5) relative to cryoablation., Conclusions: Our findings corroborated that in cT1a patients with tumor size 3.1-4 cm, cancer-specific mortality is twofold higher after heat-based thermal ablation vs cryoablation. Conversely, in patients with tumor size ≤3 cm either ablation technique is equally valid. These findings should be considered at clinical decision making and informed consent.

Purpose: Systemic therapies (ST) improved contemporary survival rates, relative to historical in clear cell metastatic renal carcinoma (ccmRCC) patients. The magnitude of this improvement is unknown according to race/ethnicity., Methods: Within the SEER registry (2000-2017), ccmRCC patients were stratified according to race/ethnicity (Caucasian, Hispanic, African American, Asian) and historical (2000-2009) vs contemporary (2010-2017) years of diagnosis. Competing risks regression (CRR) with adjustment for other-cause mortality and Poisson smoothed cumulative incidence plots addressed cancer-specific mortality (CSM)., Results: Of 10,141 mRCC patients, 4316 (43%) vs 5825 (57%) were diagnosed in historical vs contemporary era. Of 4316 historical patients, 3203 (74%) vs 593 (14%) vs 293 (7%) vs 227 (5%) were Caucasian, Hispanic, African American and Asian. Of 5825 contemporary patients, 4124 (71%) vs 977 (17%) vs 362 (6%) vs 362 (6%) were Caucasian, Hispanic, African American and Asian. Between 2000 and 2017, ST rates ranged from 12 to 57% in Caucasians, 2 to 57% in Hispanics, 33 to 50% in African Americans, 17 to 70% in Asians and universally increased toward a plateau in 2010. In Caucasians, CSM decreased from 80 to 74% vs 79 to 74% in Hispanics vs 79 to 77% in African Americans, but not in Asians (67-73%). Nonetheless, these rates translated into independent predictor status of contemporary years of diagnosis in all race/ethnicity groups: CSM hazard ratios of 0.75, 0.75, 0.73 and 0.80 in, respectively, Caucasian, Hispanic, African American and Asian., Conclusions: In all race/ethnicity groups, contemporary ST rates increased and improved CSM rates have also been recorded., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: We tested for other-cause mortality (OCM) differences according to race/ethnicity in metastatic renal cell carcinoma (mRCC). Such differences may affect treatment considerations., Methods: Within the Surveillance, Epidemiology, and End Results Research Plus repository (2000-2018), we identified clear cell (ccmRCC) and non-clear cell (non-ccmRCC) mRCC patients and stratified according to race/ethnicity: Caucasian vs. Hispanic vs. African American vs. Asian. Poisson smoothed cumulative incidence plots and competing risks regression (CRR) models addressing OCM, after adjustment for cancer-specific mortality , were fitted. Subsequently, multivariable logistic regression models tested access to cytoreductive nephrectomy (CNT) and systemic therapy (ST)., Results: Of 10,958 ccmRCC patients, 7,892 (72%), 1,743 (16%), 688 (6%), and 635 (6%) were Caucasian, Hispanic, African American, and Asian, respectively. Of 1,239 non-ccmRCC patients, 799 (64%), 106 (9%), 278 (22%), and 56 (5%) were Caucasian, Hispanic, African American, and Asian, respectively. In multivariable CRR models, OCM was higher in African Americans vs. Caucasians in ccmRCC (HR:1.55; CI:1.19-2.01; P < 0.001) and in non-ccmRCC (HR:1.54; CI:1.01-2.35; P = 0.04). In multivariable logistic regression models, African Americans with ccmRCC were less likely to undergo CNT (OR:0.72, CI:0.60-0.86; P < 0.001), but more likely to undergo ST (OR:1.34, CI:1.11-1.61; P = 0.002)., Conclusions: In this retrospective analysis, African Americans with ccmRCC and non-ccmRCC exhibited higher OCM than Caucasians. Based on higher OCM, African Americans were less likely to undergo CNT, but more likely to benefit from ST., Competing Interests: Conflict of interest The authors declare that there is no conflict of interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Multiple systemic immune-oncology (IO) combination therapies have demonstrated overall survival (OS) benefits in metastatic renal clear cell carcinoma (mRCC). However, the magnitude of benefits over time has not been compared in a structured fashion. To assess OS and progression free survival (PFS) efficacy as reflected by hazard ratios [HR]) according to the duration of follow-up over time for each of four IO combination therapies. A systematic PubMed (MEDLINE) literature review was performed (January, 1, 2016 to February, 20, 2022). Only phase III randomized clinical trials with proven OS benefit relative to sunitinib were included. These search criteria yielded four eligible RCTs: CheckMate 214 (nivolumab plus ipilimumab), Keynote 426 (pembrolizumab plus axitinib), CheckMate 9ER (nivolumab plus cabozantinib), CLEAR (lenvatinib plus pembrolizumab). OS and PFS HRs were tabulated for all four studies including all reported timepoints. Median follow-up ranged from 25-68 months for CheckMate 214 (5 timepoints), 13-43 months for Keynote 426 (3 timepoints), 18-33 months for CheckMate 9ER (3 timepoints) and 27-34 months for CLEAR (2 timepoints). Respective OS and PFS HRs were 0.68-0.72 and 0.98-0.86, 0.53-0.73 and 0.69-0.68, 0.60-0.70 and 0.51-0.56, 0.66-0.72 and 0.39-0.47 for CheckMate 214, Keynote 426, CheckMate 9ER and CLEAR. Regarding OS HRs virtually no change was recorded over time for CheckMate 214, but a decrease in magnitude occurred in the three IO-TKI remaining studies. Regarding PFS HRs, no benefit was recorded for CheckMate 214. Statistically significant benefit was recorded in the remaining IO-TKI studies. However, it also decreased with longer follow-up. It remains to be seen, whether further 'slippage' of efficacy will persist as the data matures further for all IO-TKI combinations., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: To investigate perioperative complication rates at radical nephrectomy (RN) according to inferior vena cava thrombectomy (IVC-T) status and stage (metastatic vs non-metastatic) within kidney cancer patients., Materials and Methods: We ascertained perioperative complication rates within the National Inpatient Sample database (2016-2019). First, log-link linear Generalized Estimating Equation function (GEE) regression models (adjusted for hospital clustering and weighted for discharge disposition) tested complication rates in IVC-T patients, according to metastatic stage. Subsequently, a subgroup analysis relied on RN patients with or without IVC-T. Here, multivariable logistic regression models tested complication rates in RN patients according to IVC-T status, after propensity score matching including metastatic stage., Results: Of 26,299 RN patients, 461 (2%) patients underwent IVC-T. Of those, 252 (55%) were non-metastatic vs 209 (45%) were metastatic. Rates of acute kidney injury (AKI), transfusion, cardiac, thromboembolic and other medical complications in non-metastatic vs metastatic patients were 40 vs 40%, 25 vs 22%, 21 vs 23%, 19 vs 14% and 38 vs 40%, respectively (all p ≥ 0.2). Metastatic stage in IVC-T patients did not predict differences in complications in log-link linear GEE regression models (all p > 0.1). However, in logistic regression models with propensity score matching, relying on the overall cohort of RN patients, IVC-T status was associated with higher complication rates (all p < 0.001): AKI (Odds ratio [OR]:2.60; 95%-CI [95%-Confidence interval: 1.97-3.44), transfusions (OR:2.40; 95%-CI: 1.72-3.36), cardiac (OR:2.27; 95%-CI: 1.49-3.47), thromboembolic (OR:9.07; 95%-CI: 5.21-16.58) and other medical complications (OR:2.01; 95%-CI: 1.52-2.66)., Conclusions: The current analyses indicate that presence of concomitant IVC-T is associated with higher complication rate at RN. Conversely, metastatic stage has no effect on recorded complication rates., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Data in patients with malignant melanoma, who have been previously treated with pembrolizumab as adjuvant therapy, show a reduction in pembrolizumab efficacy upon rechallenge. We examined this scenario in patients with non-metastatic renal cell carcinoma (RCC) eligible for adjuvant pembrolizumab after nephrectomy. We hypothesized that a proportion of such patients will either require re-treatment with pembrolizumab upon metastatic progression prior to cancer-specific mortality (CSM) or die from other cause mortality (OCM)., Materials and Methods: We identified within the SEER database 10,635 patients, between 2004 and 2017, with a diagnosis of non-metastatic intermediate-high and high risk RCC, who had undergone nephrectomy and fulfilled criteria for enrollment in KEYNOTE-564. Kaplan-Meier analyses addressed overall survival (OS), CSM and OCM., Results: 9,825 (92.4%) of the 10,635 patients had intermediate-high risk RCC and 9,456 (88.9%) underwent radical nephrectomy. Additionally, 760 (7.1%) harbored sarcomatoid features. In Kaplan-Meier analyses, median OS was 9.8 (9.1-11.4) years. At 10-years of follow-up, CSM rate was 36% and OCM rate was 22%., Conclusions: Based on CSM, our observations indicate that by 10-years of follow-up 36% of patients treated with adjuvant pembrolizumab will require a rechallenge, in a setting where a checkpoint inhibitor may have reduced efficacy. Moreover, at 10-years of follow-up, 22% of patients with RCC, previously treated with adjuvant pembrolizumab, will die of other causes. These percentages should be strongly considered prior to routine use of adjuvant pembrolizumab, especially given an OS benefit has not been proven., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The objective of this study was to evaluate the usefulness of pre-operative visceral (VAT) and subcutaneous adipose tissue (SAT) evaluation in the prediction of acute kidney injury (AKI) and decrease of eGFR at 12 months after radical nephrectomy (RN)., Methods: We relied on 112 patients who underwent RN between January 2010 and March 2017 at a single institution. Images from the pre-operatory CT scan were analyzed and both SAT and VAT assessments were carried out on a cross-sectional plane. eGFR was measured before surgery, at 7 days, and 12 months after surgery. ROC analysis was used to compare the diagnostic value of BMI, VAT ratio, and abdominal circumference in predicting AKI. Logistic regression models were fitted to predict the new onset of AKI, and the progression from chronic kidney disease (CKD) stage 1-3a to CKD stage 3b or from 3b to 4 at 12 months follow-up. Two logistic regression models were also performed to assess the predictors for AKI and CKD stage progression. The predictive accuracy was quantified using the receiver operating characteristic-derived area under the curve., Results: Sixty-six patients (58.9%) had AKI after RN. Thirty-five (31.3%) patients were upgraded to CKD IIIb or from CKD stage IIIb to CKD IV. In the ROC analysis, VAT% performed better than the BMI and abdominal circumference (AUC=0.66 vs. 0.49 and 0.54, respectively). At multivariable analyses, VAT reached an independent predictor status for AKI (OR: 1.03) and for CKD stage at 12-month follow-up (OR: 1.05). Inclusion of VAT% into the multivariable models was associated with the highest accuracy both for AKI (AUC=0.700 vs. 0.570) and CKD stage progression (AUC=0.848 vs. 0.800)., Conclusions: In patients undergoing RN, preoperative visceral adipose tissue ratio significantly predicts AKI incidence and is significantly predictive of 12-month CKD stage worsening.

Background: To investigate the perioperative and morbidity outcomes after partial nephrectomy (PN) in patients with short life expectancy (SLE) (≥95% 10-year expected mortality (10y-EM)), to assess the main predictors of outcomes in this population and to compare these results with those of a group at the opposite upper range with long LE (LLE, ≤5% 10y-EM) relying on a multicenter Italian prospective registry of kidney surgery (the RECORD 2 project)., Methods: Clinical data of 4,325 patients undergone kidney surgery were collected at 26 urological Italian Centers from 2013 to 2016. SLE was defined as a ≥95% 10y-EM (assessed using the age-adjusted Charlson comorbidity index [CCI]). A multivariable logistic regression for overall postoperative complications, acute kidney injury (AKI), positive surgical margins (SM) and ∆ estimated glomerular filtration rate (eGFR) ≥25% at 2 years from surgery was performed in patients with SLE including clinically relevant variables. Adjusted outcomes reported as mean (SD) of the 2 groups were generated using separate multivariable logistic regression models and compared., Results: Overall, 559 patients with SLE were selected. Patients had an ASA score ≥3 in 58.4% of cases. A clinical T1a, T1b, and T2 stage was found in 412 (74.5%), 124 (22.4%), and 17 (3.1%) patients. The median PADUA score was 7 (6-8). Surgical and medical postoperative complication rates were registered in 14.8% and 6% cases. Postoperative AKI was reported in 27.3% cases, positive surgical margins (PSM) in 9.3% cases. In this subgroup of patients, ASA score, cerebrovascular disease, surgery in low volume centers, and open surgery were independent predictors of overall complications. ASA and PADUA scores, renal clamping, resection technique and lower eGFR at baseline were independent predictors of AKI. PADUA score, open approach and resection technique were independent predictors of PSM. Cardiovascular disease, hilar clamping, and resection technique were independent predictors of eGFR decrease >25% at 2 years from surgery. Patients with SLE were compared with those with LLE (n = 302). All analyzed parameters at baseline were significantly different among the groups with the exception of cancer laterality. After adjusting for several clinical variables, the SLE group had a significantly higher risk rate of adjusted overall postoperative complication rate compared to the LLE group (20.6% ± 0.36 vs. 9.9% ± 0.65, P < 0.0001), while the overall intraoperative complications (4.1% ±0.13 vs. 2.3% ± 0.23), overall postoperative major complications (3.8% ± 0.09 vs. 1.9% ± 0.14) adjusted AKI (24.2% ± 0.37 vs. 22.6% ± 0.92), positive surgical margins (8% ± 0.22 vs. 6.4% ± 0.49), and 2-year RF loss (13.4% ± 0.17 vs. 12.4% ± 0.74)., Conclusion: In selected patients with SLE, PN is feasible with an acceptable safety profile that is overall comparable to patients with no LE limitations. While a robotic approach and surgery performed in high volume centers could reduce the risk of complications, an off-clamp approach and a SE surgical technique may decrease the risk of postoperative AKI and of longer term eGFR decrease., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: to evaluate clinical predictors of positive surgical margins (PSMs) in a large multicenter prospective observational study and to develop a clinic nomogram to predict the likelihood of PSMs after partial nephrectomy (PN)., Materials and Methods: We prospectively evaluated 4308 patients who had surgical treatment for renal tumors between January 2013 and December 2016 at 26 urological Italian Centers (RECORd 2 project). Two multivariable logistic models were evaluated to predict the likelihood of PSMs. Center caseload was dichotomized using a visual assessment adjusted for several predictors of PSMs. A nomogram predicting PSMs was developed., Results: Overall, 2076 patients treated with PN were evaluated. pT1a, pT1b, pT2 and pT3a were recorded in 68.7%, 22.6%, 2.1% and 6.6% of the patients, respectively. PSMs were recorded in 342 (16.5%) patients. From a null multivariable model against number of PN/year, 60 PN/year were identified as the best cut-off to define a high-volume centre. At multivariable analysis, clinical stage (cT1a vs. cT2 [OR 1.94]; p = 0.03), volume centre (≤60 PN/year) (OR 2.22; p < 0.0001), imperative vs elective indication (OR 2.10; p = 0.04), surgical technique (laparoscopic vs. open [OR 1.62; p = 0.002), lymphovascular invasion (OR 2.27; p = 0.01) and upstaging to pT3a (OR 2.81; p < 0.0001) were independent predictors of PSMs. The final nomogram included age, ASA score, Charlson score, clinical tumor stage, surgical indication, surgical approach, surgical technique, PADUA score, clamp procedure and volume centre., Conclusions: PSMs after PN were significantly more likely in patients with lower clinical stage, higher PADUA score, in individuals referred to laparoscopic PN and in those treated at lower volume centers. We used these data to develop a nomogram to predict such risk., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objectives: Our aim was to determine whether using an organ transplant-based(TB) approach reduces postoperative complications(PCs) following radical nephrectomy(RN) and tumor thrombectomy(TT) in renal cell carcinoma(RCC) patients with level II-IV thrombi., Methods: A total of 390(292 non-TB/98 TB) IRCC-VT Consortium patients who received no preoperative embolization/IVC filter were included. Stepwise linear/logistic regression analyses were performed to determine significant multivariable predictors of intraoperative estimated blood loss(IEBL), number blood transfusions received, and overall/major PC development within 30days following surgery. Propensity to receive the TB approach was controlled., Results: The TB approach was clearly superior in limiting IEBL, blood transfusions, and PC development, even after controlling for other significant prognosticators/propensity score(P < .000001 in each case). Median IEBL for non-TB/TB approaches was 1000 cc/300 cc and 1500 cc/500 cc for tumor thrombus Level II-III patients, respectively, with no notable differences for Level IV patients(2000 cc each). In comparing PC outcomes between non-TB/TB patients with a non-Right-Atrium Cranial Limit, the observed percentage developing a: i) PC was 65.8%(133/202) vs. 4.3%(3/69) for ECOG Performance Status(ECOG-PS) 0-1, and 84.8%(28/33) vs. 25.0%(4/16) for ECOG-PS 2-4, and ii) major PC was 16.8%(34/202) vs. 1.4%(1/69) for ECOG-PS 0-1, and 27.3%(9/33) vs. 12.5%(2/16) for ECOG-PS 2-4. Major study limitation was the fact that all TB patients were treated by a single, experienced, high volume surgeon from one center (non-TB patients were treated by various surgeons at 13 other centers)., Conclusions: Despite this major study limitation, the observed dramatic differences in PC outcomes suggest that the TB approach offers a major breakthrough in limiting operative morbidity in RCC patients receiving RN and TT., (Copyright © 2019. Published by Elsevier Ltd.)

Background/aim: Autophagy has been shown to be involved in cancer development and response to cancer therapy. In this study, genotypes of autophagic genes were analyzed to assess their correlation with the risk of clear cell renal cell carcinoma (ccRCC) and the outcome of patients treated with pazopanib for metastatic ccRCC., Materials and Methods: Single nucleotide polymorphisms (SNPs)were selected in the following genes: ATG4A (rs7880351), ATG4B (rs6709768), ATG4C (rs2886770, rs6670694, rs6683832), ATG5 (rs9373839, rs3804333, rs490010), ATG16L1 (rs6752107), ATG16L2 (rs10751215) and IRGM (rs10059011). The Kaplan-Meier method and log-rank test were used to evaluate differences between groups., Results: Forty patients with metastatic ccRCC treated with pazopanib were included in the analysis. ATG16L2rs10751215 was significantly less frequent in patients with ccRCC compared to the general population, suggesting its potential protective role, while ATG4Ars7880351, ATG4C rs6670694 and rs6683832 and ATG5 rs490010 were correlated with the progression-free survival (PFS) of patients treated with pazopanib., Conclusion: Our results suggest, for the first time, that autophagic gene SNPs are associated with ccRCC risk and patient outcome., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

We aimed to investigate the different outcomes in patients with metastatic renal cell carcinoma treated with second-line axitinib or everolimus after sunitinib. Patients treated in 16 oncological centres in Italy were included, and those receiving axitinib or everolimus from January 2013 onwards were analysed for outcomes. Descriptive statistical tests were used to highlight differences between groups. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Data on 634 patients with metastatic renal cell carcinoma treated with first-line sunitinib have been obtained. A total of 182 patients received a second-line therapy with everolimus (79 patients, 43%) or axitinib (103 patients, 57%), respectively. The median PFS was 4.6 [95% confidence (CI): 2.6-6.5] months for patients treated with everolimus and 5.5 (95% CI: 4.3-6.7) months for patients treated with axitinib (P=0.7). The median OS was 13.9 (95% CI: 10.4-17.4) months for patients treated with everolimus and 12.0 (95% CI: 7.9-16.2) months for patients treated with axitinib (P=0.3). No differences were found based on length of first-line treatment. Major limitations are the retrospective nature of the study and the lack of a prospective evaluation of the progression. This study reports no significantly differences between everolimus and axitinib in terms of both PFS and OS. Furthermore, the length of first-line treatment cannot be used as such a predictive factor and cannot suggest the use of a molecule compared with another.

Objectives: To study the effect of lymph node dissection (LND) at the time of nephrectomy and tumor thrombectomy on oncological outcomes in patients with renal cell carcinoma (RCC) and tumor thrombus., Patients and Methods: The records of 1,978 patients with RCC and tumor thrombus who underwent radical nephrectomy and tumor thrombectomy from 1985 to 2014 at 24 centers were analyzed. None of the patients had distant metastases. Extent and pathologic results of LND were compared with respect to cancer-specific survival (CSS). Multivariable Cox regression models were used to quantify the effect of multiple covariates., Results: LND was performed in 1,026 patients. In multivariable analysis, the presence of LN metastasis, the number of positive LNs, and LN density were independently associated with cancer-specific mortality (CSM). Clinical node-negative (cN-) disease was documented in 573 patients, 447 of them underwent LND with 43 cN- patients (9.6%) revealing positive LNs at pathology. LN positive cN- patients showed significantly better CSS when compared to LN positive cN+ patients. In multivariable analysis, positive cN status in LN positive patients was a significant predictor of CSM (HR, 2.923; P = 0.015)., Conclusions: The number of positive nodes harvested during LND and LN density was strong prognostic indicators of CSS, while number of removed LNs did not have a significant effect on CSS. The rate of pN1 patients among clinically node-negative patients was relatively high, and LND in these patients suggested a survival benefit. However, only a randomized trial can determine the absolute benefit of LND in this setting., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The role of lymph node dissection (LND) in renal cell carcinoma (RCC) is still under debate. We aimed to assess the utilization rates of LND over time in Europe., Methods: A multi-institutional database of 13,581 RCC patients who underwent radical nephrectomy (RN) or nephron sparing surgery (NSS) between 1988 and 2014 was created within an European consortium. We analysed temporal trends in the frequency of LND by using Joinpoint regression. Logistic regression models were used to identify predictors of LND., Results: Overall, 5114 patients (42.7%) underwent LND. Lymph node invasion was recorded in 566 cases (11% of LND patients) which represents 4.7% of the whole study cohort. A gradual decline in the use of LND started in the 1990s. After 2008 LND decreased significantly by 21.5% per year (95%CI -33.3 to -7.5, p < 0.01) until 2011 and stabilized thereafter (Annual Percentage Change 4.9%, 95%CI -3.4 to 13.8, p = 0.2). At multivariable analyses, patient age (OR 0.98, p < 0.0001), type of surgery (RN vs. NSS: OR 5.46, p < 0.0001), surgical approach (open vs. minimally invasive: OR 1.75, p < 0.0001), T stage (T2 vs. T1: OR 1.57; T3-4 vs. T1: OR 1.44, p < 0.0001), clinical tumour size (OR 1.14, p < 0.0001), and year of surgery (OR 0.95, p < 0.0001) were associated with higher probability of LND at nephrectomy., Conclusions: A trend towards lower LND was observed over time for RCC patients who underwent RN or NSS. LND is more frequently performed in younger patients, locally advanced diseases and in case of open surgery., (Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Renal cell carcinoma forming a venous tumor thrombus (VTT) in the inferior vena cava (IVC) has a poor prognosis. Recent investigations have been focused on prognostic markers of survival. Thrombus consistency (TC) has been proposed to be of significant value but yet there are conflicting data. The aim of this study is to test the effect of IVC VTT consistency on cancer specific survival (CSS) in a multi-institutional cohort., Methods: The records of 413 patients collected by the International Renal Cell Carcinoma-Venous Thrombus Consortium were retrospectively analyzed. All patients underwent radical nephrectomy and tumor thrombectomy. Kaplan-Meier estimate and Cox regression analyses investigated the impact of TC on CSS in addition to established clinicopathological predictors., Results: VTT was solid in 225 patients and friable in 188 patients. Median CSS was 50 months in solid and 45 months in friable VTT. TC showed no significant association with metastatic spread, pT stage, perinephric fat invasion, and higher Fuhrman grade. Survival analysis and Cox regression rejected TC as prognostic marker for CSS., Conclusions: In the largest cohort published so far, TC seems not to be independently associated with survival in RCC patients and should therefore not be included in risk stratification models. J. Surg. Oncol. 2016;114:764-768. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Purpose: There is no consensus regarding a protective effect on mortality due to a cause other than cancer in patients treated with elective nephron sparing surgery relative to their radical nephrectomy counterparts. We test whether the protective effect of nephron sparing surgery relative to radical nephrectomy is universal or present in specific subgroups of patients., Materials and Methods: A collaborative database of 5 institutions was queried to evaluate 1,783 patients without chronic kidney disease diagnosed with a clinical T1 renal mass that was treated with nephron sparing surgery or radical nephrectomy. Multivariable Cox regression analysis was done to assess the impact of surgery type (nephron sparing surgery vs radical nephrectomy) on other cause mortality after adjustment for patient and cancer characteristics. Interaction terms were used to test the hypothesis that the impact of surgery type varies according to specific subcohorts of patients., Results: Ten-year other cause mortality-free survival rates were 90% and 88% after nephron sparing surgery and radical nephrectomy, respectively. In the overall population radical nephrectomy was not associated with an increased risk of other cause mortality on multivariable analysis compared to nephron sparing surgery (HR 0.91, 95% CI 0.6-1.38, p = 0.6). However, radical nephrectomy increased the risk of other cause mortality according to the increasing baseline Charlson comorbidity index (interaction test p = 0.0008). For example, in a patient with a Charlson comorbidity index of 4 the probability of 10-year other cause mortality-free survival was 86% after nephron sparing surgery and 60% after radical nephrectomy., Conclusions: Elective nephron sparing surgery does not improve other cause survival relative to radical nephrectomy consistently in all patients with kidney cancer. Patients who are more ill with relevant comorbidities are those who benefit the most from nephron sparing surgery in terms of other cause mortality., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Unlabelled: A standardized histologic definition and classification of the patterns of renal tumor pseudocapsular invasion (RTPI) in renal cell carcinoma (RCC) is not available. We classified RTPI into 2 main histologic patterns: expansive and infiltrative RTPI. Patients with organ-confined RCC and infiltrative RTPI had a greater risk of cancer-specific death and might require stricter postoperative surveillance strategies., Introduction: A standardized histologic definition and classification of patterns of renal tumor pseudocapsular invasion (RTPI) in renal cell carcinoma (RCC) is not available. The aim of the present study was to propose a classification of RTPI patterns and assess their correlation with other pathologic features and prognosis., Patients and Methods: The renal tumor pseudocapsule was assessed by 2 expert genitourinary pathologists on the histologic slides of 190 specimens from radical nephrectomy performed for organ-confined (pT1-pT2) RCC. The histologic patterns of RTPI were classified and described. The association between the RTPI patterns and other pathologic features was assessed. The Kaplan-Meier method was used to calculate the survival functions, and Cox regression models were used to assess the predictors of cancer-specific survival., Results: RTPI was classified into 2 main histologic patterns (expansive and infiltrative). Expansive and infiltrative RTPI was observed in 39.5% and 51.6% of cases, respectively. A significant association between the RTPI pattern and Fuhrman grade (P = .006) and RCC histologic subtype (P = .034) was detected. Patients with infiltrative pseudocapsular invasion had significantly poorer 5- and 10-year cancer-specific survival rates than patients with expansive invasion or no invasion (93.6% vs. 98.9% and 84.9% vs. 93%, respectively; P = .039). The presence of infiltrative pseudocapsular invasion was a significant predictor of cancer-specific survival (hazard ratio 4.38, 95% confidence interval 1.04-20.27)., Conclusion: An expansive and an infiltrative RTPI pattern can be described. In our study, patients with organ-confined RCC and an infiltrative RTPI pattern had a greater risk of cancer-specific death and might require stricter postoperative surveillance strategies., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: The impact of cardiopulmonary bypass in level III-IV tumor thrombectomy on surgical and oncologic outcomes is unknown. We determine the impact of cardiopulmonary bypass on overall and cancer specific survival, as well as surgical complication rates and immediate outcomes in patients undergoing nephrectomy and level III-IV tumor thrombectomy with or without cardiopulmonary bypass., Materials and Methods: We retrospectively analyzed 362 patients with renal cell cancer and with level III or IV tumor thrombus from 1992 to 2012 at 22 U.S. and European centers. Cox proportional hazards models were used to compare overall and cancer specific survival between patients with and without cardiopulmonary bypass. Perioperative mortality and complication rates were assessed using logistic regression analyses., Results: Median overall survival was 24.6 months in noncardiopulmonary bypass cases and 26.6 months in cardiopulmonary bypass cases. Overall survival and cancer specific survival did not differ significantly in both groups on univariate analysis or when adjusting for known risk factors. On multivariate analysis no significant differences were seen in hospital length of stay, Clavien 1-4 complication rate, intraoperative or 30-day mortality and cancer specific survival. Limitations include the retrospective nature of the study., Conclusions: In our multi-institutional analysis the use of cardiopulmonary bypass did not significantly impact cancer specific survival or overall survival in patients undergoing nephrectomy and level III or IV tumor thrombectomy. Neither approach was independently associated with increased mortality on multivariate analysis. Greater surgical complications were not independently associated with the use of cardiopulmonary bypass., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to evaluate the predictors of positive margins in one of the largest available prospective multi-institutional studies., Patients and Methods: We evaluated all patients who underwent NSS for radiologically diagnosed kidney tumors between January 2009 and December 2012 at 19 urological Italian centers (Registry of Conservative Renal Surgery [RECORd] project). Preoperative and anthropometric data, comorbidities, intraoperative and postoperative outcomes, and histological findings were analyzed. The negative and PSMs were compared according to the clinical and surgical variables. Multivariable logistic regression models were applied to analyze predictors of PSMs., Results: Eight hundred consecutive patients were evaluated. Seven hundred sixty-one (95.1%) and 39 patients (4.9%) achieved negative and PSMs, respectively. Patients with PSMs were significantly older compared with those with negative margins (median age: 66.6 vs. 61.8 years, respectively; P = .001). A higher incidence of PSMs was observed when NSS was performed for renal masses located in the upper pole (P = .001). A lower rate of PSMs was found in patients treated with simple enucleation rather than standard PN (1.6% vs. 7.4%, respectively; P < .0001). A greater incidence of PSMs was found in Fuhrman 3/4 tumors (11.3%; P < .0001). At multivariable analysis, age (odds ratio [OR], 1.04; P = .01), upper pole tumor location (OR, 2.85; P = .005), standard PN (OR, 3.45; P = .004), and Fuhrman 3-4 nuclear grade (OR, 4.81; P = .001) were found to be independent predictors of PSMs., Conclusion: In our multi-institutional report, young age, simple enucleation, middle or lower tumor location, and low-grade tumor were demonstrated to be independent predictors of negative SMs., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: Nephron-sparing surgery (NSS) has become the standard of care for the surgical management of small and clinically localized renal cell carcinoma (RCC). The conservative management of those RCCs is increasing over time. Aim of this study was to report a snapshot of the clinical, perioperative and oncological results after NSS for RCC in Italy., Material and Methods: We evaluated all patients who underwent conservative surgical treatment for renal tumours between January 2009 and December 2012 at 19 urological Italian Centers (RECORd project). Perioperative, radiological and histopathological data were recorded. Surgical eras (2009 vs 2012 and year periods 2009-2010 vs 2011-2012) were compared., Results: Globally, 983 patients were evaluated. More recently, patients undergoing NSS were found to be significantly younger (p = 0.05) than those surgically treated in the first study period, with a significantly higher rate of NSS with relative and imperative indication (p < 0.001). More recently, a higher percentage of procedures for cT1b or cT2 renal tumours was observed (p = 0.02). Utilization rate of open partial nephrectomy (OPN) constantly decreased during years, laparoscopic partial nephrectomy (LPN) remained almost constant while robot-assisted partial nephrectomy (RAPN) increased. The rate of clampless NSS constantly increased over time. The use of at least one haemostatic agent has been significantly more adopted in the most recent surgical era (p < 0.001)., Conclusions: The utilization rate of NSS in Italy is increasing, even in elective and more complex cases. RAPN has been progressively adopted, as well as the intraoperative utilization of haemostatic agents and the rate of clampless procedures., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: Metastatic renal cell carcinoma can be clinically diverse in terms of the pattern of metastatic disease and response to treatment. We studied the impact of metastasis and location on cancer specific survival., Materials and Methods: The records of 2,017 patients with renal cell cancer and tumor thrombus who underwent radical nephrectomy and tumor thrombectomy from 1971 to 2012 at 22 centers in the United States and Europe were analyzed. Number and location of synchronous metastases were compared with respect to patient cancer specific survival. Multivariable Cox regression models were used to quantify the impact of covariates., Results: Lymph node metastasis (155) or distant metastasis (725) was present in 880 (44%) patients. Of the patients with distant disease 385 (53%) had an isolated metastasis. The 5-year cancer specific survival was 51.3% (95% CI 48.6-53.9) for the entire group. On univariable analysis patients with isolated lymph node metastasis had a significantly worse cancer specific survival than those with a solitary distant metastasis. The location of distant metastasis did not have any significant effect on cancer specific survival. On multivariable analysis the presence of lymph node metastasis, isolated distant metastasis and multiple distant metastases were independently associated with cancer specific survival. Moreover higher tumor thrombus level, papillary histology and the use of postoperative systemic therapy were independently associated with worse cancer specific survival., Conclusions: In our multi-institutional series of patients with renal cell cancer who underwent radical nephrectomy and tumor thrombectomy, almost half of the patients had synchronous lymph node or distant organ metastasis. Survival was superior in patients with solitary distant metastasis compared to isolated lymph node disease., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Although different prognostic factors for patients with renal cell carcinoma (RCC) and vena cava tumor thrombus (TT) have been studied, the prognostic value of histologic subtype in these patients remains unclear., Objective: We analyzed the impact of histologic subtype on cancer-specific survival (CSS)., Design, Settings, and Participants: We retrospectively analyzed the records of 1774 patients with RCC and TT who underwent radical nephrectomy and tumor thrombectomy from 1971 to 2012 at 22 US and European centers., Outcome Measurements and Statistical Analysis: Multivariable ordered logistic and Cox regression models were used to quantify the impact of tumor histology on CSS., Results and Limitations: Overall 5-yr CSS was 53.4% (confidence interval [CI], 50.5-56.2) in the entire group. TT level (according to the Mayo classification of macroscopic venous invasion in RCC) was I in 38.5% of patients, II in 30.6%, III in 17.3%, and IV in 13.5%. Histologic subtypes were clear cell renal cell carcinoma (cRCC) in 89.9% of patients, papillary renal cell carcinoma (pRCC) in 8.5%, and chromophobe RCC in 1.6%. In univariable analysis, pRCC was associated with a significantly worse CSS (p<0.001) compared with cRCC. In multivariable analysis, the presence of pRCC was independently associated with CSS (hazard ratio: 1.62; CI, 1.01-2.61; p<0.05). Higher TT level, positive lymph node status, distant metastasis, and fat invasion were also independently associated with CSS., Conclusions: In our multi-institutional series, we found that patients with pRCC and vena cava TT who underwent radical nephrectomy and tumor thrombectomy had significantly worse cancer-specific outcomes when compared with patients with other histologic subtypes of RCC. We confirmed that higher TT level and fat invasion were independently associated with reduced CSS., (Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Renal cell carcinoma (RCC) extension into the renal vein or the inferior vena cava occurs in 4%-10% of all kidney cancer cases. This entity shows a wide range of different clinical and surgical scenarios, making natural history and oncological outcomes variable and poorly characterized. Infrequency and variability make it necessary to share the experience from different institutions to properly analyze surgical outcomes in this setting. The International Renal Cell Carcinoma-Venous Tumor Thrombus Consortium was created to answer the questions generated by competing results from different retrospective studies in RCC with venous extension on current controversial topics. The aim of this article is to summarize the experience gained from the analysis of the world's largest cohort of patients in this unique setting to date.

Background: Renal cell carcinoma (RCC) follows a variable clinical course related to disease stage and metastatic spread (including to bone). Molecular and genetic factors bear prognostic significance in RCC, including proteins involved in extracellular matrix invasion. Among these, bone sialoprotein (BSP) and osteopontin (OPN) are physiologically implicated in bone metabolism, and have a prognostic role in several tumors. BSP expression was also predictive of bone spread propensity in lung and prostate carcinoma. In RCC, no data are available for BSP, while OPN has been correlated with tumor stage, grade and survival. We aimed to define the predictive (of bone spread) and prognostic role of BSP and OPN immunohistochemical expression in clear cell RCC., Materials and Methods: from a series of 305 renal tumors resected between 1993 and 2002, 75 surgically resected clear cell RCCs with tissue material, clinical data and follow-up information available, were selected for the preliminary series; a second group of 126 chemo-naïve, radically-resected, consecutive RCCs was collected as a validation series. Immunohistochemical expression of BSP and OPN on paraffinized samples was evaluated by H-score [=Σ (intensity × percentage of positively stained cells)]., Results: In the preliminary series, BSP and OPN reactivity was found in 85% and 77% of cases, respectively. No predictive role of bone spread propensity of RCC was identified. Conversely, both BSP and OPN were significantly associated with shorter survival considering median (p=0.002) and upper quartile (p=0.03) expression values, respectively. In the validation group, a prognostic role was confirmed for BSP only (p=0.008), while OPN showed a trend of association with poorer survival (borderline p-value of 0.058)., Conclusion: BSP was shown for the first time to be an independent parameter associated with poor prognosis in RCC. Its coexpression with OPN identifies a subgroup of RCC having the worst outcome.

Unlabelled: Study Type - Outcomes (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? About 80% of RCCs have clear cell histology, and consistent data are available about the clinical and histological characteristics of this histological subtype. Conversely, less attention has been dedicated to the study of non-clear cell renal tumours Specifically, published data show that chromophobe RCC (ChRCC) have often favourable pathological stages and better nuclear grades as well as a lower risk of metastasizing compared with clear cell RCC (ccRCC). Patients with ChRCC were shown to have significantly higher cancer-specific survival (CSS) probabilities compared with ccRCC. However, an independent prognostic role of RCC histotype was not confirmed in some large multicenter series and only a few studies have focused on the oncological outcomes of ChRCC. The present study is one of the few to evaluate cancer-related outcomes of ChRCC and represents to our knowledge the largest series of ChRCCs. Consequently, the present findings may assist in elucidating the natural history of surgically treated ChRCC. The present study confirms that ChRCCs have good prognosis and a low tendency to progress and metastasize. Only 1.3% of patients presented with distant metastases at diagnosis, and the 5- and 10-year CSS were 93% and 88.9%, respectively. However, although ChRCCs are generally characterised by an excellent prognosis, we observed that patients with locally advanced or metastatic cancers as well as those with sarcomatoid differentiation have a poor outcome. The study also investigated prognostic factors for recurrence-free survival (RFS) and CSS for this RCC histotype. The definition of outcome predictors can be useful for patient counselling, planning of follow-up strategies, and patient selection for clinical trials. In the present study, gender, clinical T stage, pathological T stage, and presence of sarcomatoid differentiation were significantly associated with RFS and CSS at multivariable analysis. We also identified N/M stage as an independent predictor of CSS. Notably, as Fuhrman grade was not an independent predictor of cancer-related outcomes, the present study confirms that this histological variable is not a reliable prognostic factor for ChRCC., Objectives: To investigate cancer-related outcomes of chromophobe renal cell carcinoma (ChRCC) in a large multicentre dataset. To determine prognostic factors for recurrence-free survival (RFS) and cancer-specific survival (CSS) for this RCC histological type., Patients and Methods: In all, 291 patients with ChRCC were identified from a multi-institutional retrospective database including 5463 patients who were surgically treated for RCC at 16 Italian academic centres between 1995 and 2007. Univariable and multivariable Cox regression models were used to identify prognostic factors predictive of RFS and CSS after surgery for ChRCC., Results: At a median follow-up of 44 months, 25 patients (8.6%) had disease recurrence and 18 patients (6.2%) died from disease. The 5-year RFS and CSS rates were 89.3% and 93%, respectively. Gender (P= 0.014), clinical T stage (P= 0.017), pathological T stage (P= 0.003), and sarcomatoid differentiation (P= 0.032) were independent predictors of RFS at multivariable analysis. For CSS, there was an independent prognostic role for gender (P= 0.032) and T stage (P= 0.019) among the clinical variables and for T stage (P= 0.016), N/M stage (P= 0.023), and sarcomatoid differentiation (P= 0.015) among the pathological variables., Conclusions: Patients with ChRCC have a low risk of tumour progression, metastasis, and cancer-specific death. Patient gender, clinical and pathological tumour stage, and sarcomatoid differentiation are significant predictors of RFS and CSS for ChRCC., (© 2011 BJU INTERNATIONAL.)

Objectives: To investigate cancer-related outcomes and prognostic factors of papillary renal cell carcinoma (pRCC) in a large multicentre data set. Oncological outcome and prognostic factors of pRCC have been limitedly evaluated in comparison with the most common RCC subtype, clear cell RCC., Patients and Methods: From a multicentre retrospective database, including 5463 patients who were surgically treated for RCC at 16 Italian academic centres between 1995 and 2007, 577 patients with pRCC were identified. Univariable and multivariable Cox regression models were performed to identify prognostic factors predictive of recurrence-free survival (RFS) and cancer-specific survival (CSS) after surgery., Results: At a median (interquartile range) follow-up of 39.2 (21.7-72) months, 81 (14%) patients had experienced disease progression and 63 (11%) patients had died from disease; the 5-year RFS estimate was 85.5%. In multivariable analysis, pathological N stage (pooled P < 0.001), M stage (hazard ratio, 2.9; P= 0.007) and Fuhrman nuclear grade (pooled P= 0.039) were all independent predictors of RFS; the 5-year CSS estimate was 87.9%. In Cox multivariable analysis, an independent predictive role was reconfirmed for mode of presentation (pooled P= 0.038), pathological N stage (pooled P < 0.001), M stage (hazard ratio, 2.4; P= 0.049) and Fuhrman nuclear grade (pooled P= 0.037)., Conclusions: Patients with pRCC have a low risk of tumour recurrence and cancer-related death after surgery. Fuhrman nuclear grade was found to be a stronger predictor of both RFS and CSS, whereas only a non-statistically significant trend was found for the 2009 pathological T stage., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Objective of the study is to review the current 7th edition of the TNM classification of renal tumors and to perform a critical analysis of the recent evidence in order to identify the limitations of this new staging system. A search of the english literature was performed through the Medline and Pubmed database using the following keywords: renal cell carcinoma, staging system and TNM. Overall, 2600 references were initially scrutinized. Forty papers were selected based on their pertinence with the topic of the review, level of evidence provided and overall contribution to the field. Few changes have been made in the current version of the TNM staging system of renal tumors. pT2 tumors have been divided in 2 subgroups based on tumor size with a cut-off at 10 cm; the invasion of the renal vein was classified as pT3a; finally, the invasion of the ispsilateral adrenal gland was classified as pT4. However, other changes were suggested by the analysis of the recent literature and have not been introduced in this new version. Further improvements of the TNM classification for renal tumors are needed especially with regard to locally advanced tumors and node-positive disease, in order to improve the accuracy of this important prognostic tool in renal oncology.

Background: The prognostic significance of venous involvement and tumour thrombus level in renal cell carcinoma (RCC) remains highly controversial. In 2010, the American Joint Committee on Cancer (AJCC) and the Union International Centre le Cancer (UICC) revised the RCC staging system (7th edition) based on tumour thrombus level, differentiating the T stage of tumours limited to renal-vein-only involvement., Objective: We aimed to evaluate the impact of tumour thrombus extension in a multi-institutional cohort of patients., Design, Setting, and Participants: An international consortium of 11 institutions was established to retrospectively review a combined cohort of 1215 patients undergoing radical nephrectomy and tumour thrombectomy for RCC, including 585 patients with inferior vena cava (IVC) involvement or higher., Measurements: Predictive factors of survival, including histology, tumour thrombus level, nodal status, Fuhrman grade, and tumour size, were analysed., Results and Limitations: A total of 1122 patients with complete data were reviewed. The median follow-up for all patients was 24.7 mo, with a median survival of 33.8 mo. The 5-yr survival was 43.2% (renal vein involvement), 37% (IVC below the diaphragm), and 22% with caval involvement above the diaphragm. On multivariate analysis, tumour size (hazard ratio [HR]: 1.64 [range: 1.03-2.59]; p=0.036), Fuhrman grade (HR: 2.26 [range: 1.65-3.1]; p=0.000), nodal metastasis (HR: 1.32 [range: 1.09-1.67]; p=0.005), and tumour thrombus level (HR: 2.10 [range: 1.53-3.0]; p=0.00) correlated independently with survival., Conclusions: Based on analysis of the largest known cohort of patients with RCC along with IVC and atrial thrombus involvement, tumour thrombus level is an independent predictor of survival. Our findings support the changes to the latest AJCC/UICC staging system., (Copyright © 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

The role of percutaneous biopsy of renal masses has been traditionally limited by concerns about its safety, accuracy and sampling errors. The increasing incidence in the diagnosis of incidental small renal masses (SRMs), the development of conservative and minimally invasive treatments for low risk renal cell carcinomas (RCCs) and the discovery of novel targeted treatments for metastatic disease are now leading to wider indications for renal tumor biopsy. Percutaneous biopsy of renal tumors can be performed in an outpatient setting under ultrasound and/or CT guidance. 18 gauge needles loaded in an automatic biopsy gun are used to retrieve cores and 21 gauge needles to obtain FNA specimens through a 17 gauge coaxial cannula placed close to the tumor. A careful check of the quality of biopsies and aspirates is paramount to maximize the diagnostic yield of the procedure. With the development of new biopsy techniques the risk of tumor seeding appears negligible and significant bleeding is unusual and very rarely clinically significant. In centres with expertise, needle core biopsy with or without FNA can provide adequate specimens for an accurate diagnosis in over 90% of cases. Incidental SRMs are frequently detected in elderly patients and have a very heterogeneous biological behaviour At surgery up to one third have benign histologies and most of those that are malignant are low grade RCCs. Pretreatment percutaneous biopsy can significantly decrease the number of unnecessary surgeries for benign disease and assist the urologist in clinical decision making, especially for elderly and unfit patients who are possible candidates for active surveillance and/or minimally invasive ablative therapies. Finally, there is potential for stratifying initial therapy of metastatic RCC by histological subtype on needle biopsies.

Objective: To prospectively assess the clinical outcome of a series of papillary renal cell carcinomas (PRCCs) to identify possible prognostic clinical variables and tumour markers, as previous retrospective series of PRCC do not provide unanimous results on the prognostic utility of clinicopathological variables., Patients and Methods: Forty-six patients with PRCC (median follow-up 40 months) diagnosed in one institution from 1989 to 2002 were prospectively followed until May 2006. The pathology was reviewed, the PRCC subtyped (type 1 and 2) and immunohistochemistry assessed for MIB-1, vascular endothelial growth factor (VEGF), CD31 and c-met oncogenic protein, by a referee pathologist. Prognostic values were estimated by fitting a Cox model., Results: The 5-year survival rate was 49.5%; type 2 histology was predominant and was almost significant in the univariate analysis. Stage and MIB-1 were significant prognostic factors only in the univariate model, while the Cox model identified only the Fuhrman grade as an independent predictor of survival (hazard ratio 3.054; P = 0.007). MET expression, CD31 and VEGF had no prognostic utility., Conclusion: These patients with PRCC followed prospectively fared worse than in previously reported series. The Fuhrman grade was the sole independent predictor of survival.

Purpose: The prognostic accuracy of the current TNM 2002 staging system for locally advanced renal cell carcinoma has been questioned. To contribute to the development of a more accurate classification for this stage of disease we assessed the correlation between patterns of invasion in the pT3 category and outcomes in a large multi-institutional series., Materials and Methods: Pathological data and clinical followup on 513 pT3 renal cell carcinoma cases treated with radical nephrectomy between 1983 and 2005 at 3 Italian academic centers were retrospectively reviewed. Cause specific survival rates were calculated with the Kaplan-Meier method and multivariate analysis was performed using the Cox proportional hazards regression model., Results: Estimated overall 5-year cause specific survival was 50.1% at a median followup of 61.5 months in survivors. The current TNM classification was not a significant outcome prognosticator. Patients with a tumor invading only the perirenal or sinus fat were at lowest risk for death from the disease. Patients at intermediate risk had tumors with invasion of the venous system alone. Simultaneous perirenal fat and sinus fat invasion or perirenal fat and vascular invasion as well as adrenal gland involvement characterized high risk tumors. Low risk tumors could be further divided into 2 groups with different outcomes based on a size cutoff of 7 cm. Our classification was a significant predictor of survival on multivariate analysis as well as M stage, N stage, Fuhrman grade and tumor size., Conclusions: We confirm that the prognostic usefulness of the current 2002 TNM system for pT3 renal cell carcinoma is limited. We have identified 4 groups of tumors with distinct patterns of invasion and significantly different survival probabilities in this category. Large prospective series are needed to validate these findings.

Objective: The most commonly used staging system for renal cell carcinoma (RCC) is the tumor-node-metastasis (TNM) system. In the most recent TNM edition, lymph node (LN) involvement is defined as pN0, pN1, or pN2, depending on the number of metastatic LNs (none, 1, or >1). This study evaluated the prognostic value of this classification and tried to improve its clinical impact by considering an additional parameter, that is, LN density (ratio between number of positive LNs and total number of LNs retrieved)., Methods: All pathologic reports of radical nephrectomies performed for RCC in two urologic centers between November 1983 and December 1999 were reviewed. For each patient, complete clinical and pathologic data, number of LNs removed, location and number of positive LNs, and LN density were recorded. The Kaplan-Meyer method and the log-rank test were used to calculate cause-specific survival rates and to compare survival curves, respectively., Results: A total of 735 patients underwent radical nephrectomy. Lymphadenectomy was performed in 618 cases, and the rate of positive LNs was 14.2%. The 5-yr cause-specific survival rate of pN+ patients was 18%, with no statistically significant difference between pN1 and pN2. The average number of LNs removed was 13 (range, 1-35). The median number of LNs involved was 3 (range, 1-18). LN density ranged between 3.7% and 100% (median, 22.9%). The number of LNs removed had no impact on survival in pN+ patients. The only significant unfavorable prognostic factors were >4 LNs involved (p = 0.02) and LN density >60% (p = 0.01)., Conclusion: The results show that in RCC the current TNM stratification of positive LNs is not significantly correlated with prognosis. From our data it appears that classification as < or =4 or >4 LNs involved, supported by LN density, better reflects the impact of the disease on survival.

Purpose: We compared the status of the peritumoral parenchyma after open and laparoscopic nephron sparing surgery for renal cell carcinoma., Materials and Methods: The records of 64 consecutive patients who underwent nephron sparing surgery for renal cell carcinoma of 4 cm or less were reviewed retrospectively. Patients in group 1 underwent open retroperitoneal surgery (1998 to 2000) and patients in group 2 underwent laparoscopic (transperitoneal or retro peritoneal) surgery (2001 to March 2004). A single pathologist was employed to analyze the specimens, and comparative analysis included examination of tumor size, weight, histological cell type, intraoperative histological biopsies and margin status., Results: The 2 groups were comparable in terms of clinical data, and mean lesion size was 31.4 mm in group 1 and 32 mm in group 2. Positive margins were found in 1 of 30 patients in group 1 and in 1 of 34 in group 2 (p = 0.9). An analysis of margins was performed by taking measurements at the minimum and maximum points of the section. The minimum mean measurement was 2 mm in group 1 and 2.08 mm in group 2 (p = 0.75). The maximum mean measurement was 4.56 mm in group 1 and 5.2 mm in group 2 (p = 0.09). The difference between minimum and maximum margin thickness was 2.56 mm in group 1 and 3.16 mm in group 2 (p = 0.04). Mean followup for group 1 was 50 months (range 30 to 72) and 16 months (range 2 to 35) for group 2. One local recurrence was recorded in group 1 and treated with radical nephrectomy, while no recurrence was recorded in group 2., Conclusions: In this study we further confirmed the efficiency of resectioning lesions using laparoscopy. In our experience there is no difference between the 2 procedures in terms of efficient surgical margins. However, despite these encouraging results it is necessary to obtain more extensive followup data, which will allow us to be more specific in reporting on laparoscopic margin quality.

Objectives: The prognostic role of the invasion of the urinary collecting system (UCS) by renal cell carcinoma (RCC) has not attracted a notable amount of attention. The aim of this study was to investigate incidence and prognostic value of UCS involvement in RCC., Material and Methods: All pathological reports of radical nephrectomies performed in two centres of urology from November 1983 to December 1999 were reviewed in order to evaluate the invasion of the UCS (calices, renal pelvis, ureter). Patients were divided into two groups according to presence (Group 1) or absence (Group 2) of UCS invasion. The stage was determined according to the TNM 6th edition. Overall and cause-specific survival rates were evaluated. Univariate and multivariate analyses were performed., Results: The evaluable specimens were 671 from the 735 examined; in 64 cases it was not possible to ascertain or to exclude UCS involvement. Invasion of the UCS was found in 59 cases (8.8%). Median follow-up was 59.0 months (range 0-216). Tumours invading the UCS were usually symptomatic, with high nuclear grade and predominantly high stage. At univariate analysis the 5 year overall and cause-specific survival rates of tumours invading the UCS were significantly lower when compared to those without UCS invasion (42.8% versus 60.8% and 45.5% versus 64.7%, respectively). When groups were stratified, according to the pT category, the 5-year cause-specific survival rate was only significantly different for the pT2 category (33.3% versus 76.9%). At the multivariate analysis TNM staging, symptoms at diagnosis and tumour grade were the only independent prognostic factors., Conclusion: The invasion of the UCS by RCC is unusual, particularly in small tumours. UCS involvement does not represent an independent prognostic factor. However, in organ-confined tumours (i.e. pT2) UCS involvement has an influence on the prognosis and should be taken into account when planning adjuvant treatments and follow-up.

The occurrence of renal cell carcinoma is an exceptional phenomenon in an ectopic kidney. We describe a patient with renal cell cancer of the pelvic kidney who underwent radical nephrectomy at our institute. Preoperatively the patient underwent paramagnetic medium-enhanced magnetic resonance that provided an accurate description of the ectopic renal vessels. During surgery the anatomy of the vessels appeared exactly as described by the MR examination. Histological examination revealed a pT2N0GIV renal cell cancer. Nine months later the patient underwent control examinations, and no delayed complications had occurred. In our experience magnetic resonance provided an exact description of the ectopic kidney vascularization as confirmed by the surgical findings. Preoperative knowledge is important both for the surgeon during the dissection of the vessels and to plan correct lymphadenectomy on the basis of the vessel source identified at imaging., (Copyright 2004 S. Karger AG, Basel)