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Purpose: There is sparse evidence on outcomes of resected occult LN metastases at the time of nephrectomy (synchronous disease). We sought to analyse a large international cohort of patients and to identify clinico-pathological predictors of long-term survival., Materials and Methods: We collected data of consecutive patients who underwent nephrectomy and LND for T any cN0-1pN1 and cM0-1 RCC at 7 referral centres between 1988 and 2019. Patients were stratified into four clinico-pathological groups: (1) cN0cM0-pN1, (2) cN1cM0-pN1(limited, 1-3 positive nodes), (3) cN1cM0-pN1(extensive, > 3 positive nodes), and (4) cM1-pN1. Overall survival (OS) was estimated using the Kaplan-Meier method, and associations with all-cause mortality (ACM) were evaluated using Cox models with multiple imputations., Results: Of the 4370 patients with LND, 292 patients with pN1 disease were analysed. Median follow-up was 62 months, during which 171 patients died. Median OS was 21 months (95% CI 17-30 months) and the 5-year OS rate was 24% (95% CI 18-31%). Patients with cN0cM0-pN1 disease had a median OS of 57 months and a 5-year OS rate of 43%. 5-year OS (median OS) decreased to 29% (33 months) in cN1cM0-pN1(limited) and to 23% (23 months) in cN1cM0-pN1(extensive) patients. Those with cM1-pN1 disease had the worst prognosis, with a 5-year OS rate of 13% (9 months). On multivariable analysis, age (p = 0.034), tumour size (p = 0.02), grade (p = 0.02) and clinico-pathological group (p < 0.05) were significant predictors of ACM., Conclusion: Depending on clinico-pathological group, grade and tumour size, 5-year survival of patients with LN metastases varies from 13 to 43%. Patients with resected occult lymph node involvement (cN0/pN1 cM0) have the best prognosis with a considerable chance of long-term survival., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Purpose: To investigate the natural history and follow-up after kidney tumor treatment of Von Hippel-Lindau (VHL) patients., Materials and Methods: A multi-institutional European consortium of patients with VHL syndrome included 96 non-metastatic patients treated at 9 urological departments (1987-2018). Descriptive and survival analyses were performed., Results and Limitations: Median age at VHL diagnosis was 34 years (IQR 25-43). Two patients (2.1%) showed only renal manifestations at VHL diagnosis. Concomitant involvement of Central Nervous System (CNS) vs. pancreas vs. eyes vs. adrenal gland vs. others were present in 60.4 vs. 68.7 vs. 30.2 vs. 15.6 vs. 15.6% of patients, respectively. 45% of patients had both CNS and pancreatic diseases alongside kidney. The median interval between VHL diagnosis and renal cancer treatment resulted 79 months (IQR 0-132), and median index tumor size leading to treatment was 35.5 mm (IQR 28-60). Of resected malignant tumours, 73% were low grade. Of high-grade tumors, 61.1% were large > 4 cm. With a median follow-up of 8 years, clinical renal progression rate was 11.7% and 29.3% at 5 and 10 years, respectively. Overall mortality was 4% and 7.5% at 5 and 10 years, respectively. During the follow-up, 50% of patients did not receive a second active renal treatment. Finally, 25.3% of patients had CKD at last follow-up., Conclusions: Mean period between VHL diagnosis and renal cancer detection is roughly three years, with significant variability. Although, most renal tumors are small low-grade, clinical progression and mortality are not negligible. Moreover, kidney function represents a key issue in VHL patients., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Introduction: Recent trials have emphasized the importance of a precise patient selection for cytoreductive nephrectomy (CN). In 2013, a nomogram was developed for pre- and postoperative prediction of the probability of death (PoD) after CN in patients with metastatic renal cell carcinoma. To date, the single-institutional nomogram which included mostly patients from the cytokine era has not been externally validated. Our objective is to validate the predictive model in contemporary patients in the targeted therapy era., Methods: Multi-institutional European and North American data from patients who underwent CN between 2006 and 2013 were used for external validation. Variables evaluated included preoperative serum albumin and lactate dehydrogenase levels, intraoperative blood transfusions (yes/no) and postoperative pathologic stage (primary tumour and nodes). In addition, patient characteristics and MSKCC risk factors were collected. Using the original calibration indices and quantiles of the distribution of predictions, Kaplan-Meier estimates and calibration plots of observed versus predicted PoD were calculated. For the preoperative model a decision curve analysis (DCA) was performed., Results: Of 1108 patients [median OS of 27 months (95% CI 24.6-29.4)], 536 and 469 patients had full data for the validation of the pre- and postoperative models, respectively. The AUC for the pre- and postoperative model was 0.68 (95% CI 0.62-0.74) and 0.73 (95% CI 0.68-0.78), respectively. In the DCA the preoperative model performs well within threshold survival probabilities of 20-50%. Most important limitation was the retrospective collection of this external validation dataset., Conclusions: In this external validation, the pre- and postoperative nomograms predicting PoD following CN were well calibrated. Although performance of the preoperative nomogram was lower than in the internal validation, it retains the ability to predict early death after CN.

Purpose: To test the hypothesis that cytoreductive nephrectomy (CN) improves overall survival (OS) of patients with synchronous metastatic renal cell carcinoma (mRCC), who subsequently receive targeted therapies (TT)., Methods: We identified 261 patients who received TT for synchronous mRCC with or without prior CN. To achieve balance in baseline characteristics between groups, we used the inverse probability of treatment weighting (IPTW) method. We conducted OS analyses, including IPTW-adjusted Kaplan-Meier curves, Cox regression models, interaction term, and landmark and sensitivity analyses., Results: Of the 261 patients, 97 (37.2%) received CN and 164 (62.8%) did not. IPTW-adjusted analyses showed a statistically significant OS benefit for patients treated with CN (HR 0.63, 95% CI 0.46-0.83, P = 0.0015). While there was no statistically significant difference in OS at 3 months (P = 0.97), 6 months (P = 0.67), and 12 months (P = 0.11) from diagnosis, a benefit for the CN group was noted at 18 months (P = 0.005) and 24 months (P = 0.004). On interaction term analyses, the beneficial effect of CN increased with better performance status (P = 0.06), in women (P = 0.03), and in patients with thrombocytosis (P = 0.01)., Conclusions: IPTW-adjusted analysis of our patient cohort suggests that CN improves OS of patients with synchronous mRCC treated with TT. On the whole, the survival difference appears after 12 months. Specific subgroups may particularly benefit from CN, and these subgroups warrant further investigation in prospective trials.

Objective: To assess the association of smoking status with standard clinicopathological features and overall survival (OS) in a large multi-institutional cohort of patients with metastatic renal cell carcinoma (mRCC) treated with cytoreductive nephrectomy (CNT)., Methods: A total of 613 patients with mRCC treated with CNT in US and Europe institutions between 1990 and 2013 were included. Smoking history comprised smoking status, smoking duration in years, number of cigarettes per day and years since smoking cessation. Cumulative smoking exposure was categorized as light short term, heavy long term and moderate. Association between smoking history and OS was assessed by Cox regression logistic analysis., Results: One hundred and seventy-one patients (27.9 %) never smoked, 193 (31.5 %) were former smokers and 249 (40.6 %) were current smokers. Smoking status was associated with a higher number of metastases (p < 0.001) and an abnormal preoperative corrected calcium level (p = 0.01). Median follow-up was 16 (IQR 7-24) months. Current smokers had a shorter OS than never and former smokers (log rank, p = 0.004). Smoking status was significantly associated with OS in univariable analysis (HR 1.45; 95 % CI 1.16-1.82; p < 0.001), and in multivariable analysis that adjusted for established prognostic factors (HR 1.46; 95 % CI 1.16-1.84; p = 0.002). Daily consumption of more than 20 cigarettes, more than 20 years of smoking exposure and heavy long exposure were all independent prognosticators of worse OS., Conclusions: Current smoking and a higher cumulative smoking exposure are associated with a higher risk of death in patients with mRCC treated with CNT. Even at this stage, smoking negatively affects kidney cancer outcomes.

Background: Excision repair cross-complementing 1 (ERCC1) has been associated with outcomes of urothelial carcinoma of the bladder, but was not yet studied in upper tract urothelial carcinoma (UTUC). The aim of this study was to assess the prognostic role of ERCC1 expression in a large international cohort of UTUC patients., Methods: Immunohistochemical ERCC1 expression was evaluated in 716 UTUC patients who underwent radical nephroureterectomy with curative intent. ERCC1 was considered positive when the H-score was >1.0. Associations with overall survival and cancer-specific survival were assessed using univariable and multivariable Cox models., Results: ERCC1 was expressed in 303 tumors (42.3 %) and linked with the presence of tumor necrosis (16.2 vs. 10.4 %, p = 0.023), but not with any other clinical or pathological variable. ERCC1 status did not predict cancer-specific survival and overall survival on both univariable (p = 0.70 and 0.32, respectively) and multivariable analyses (p = 0.48 and 0.33, respectively)., Conclusions: ERCC1 is expressed in a significant proportion of UTUC and is linked with tumor necrosis, but its expression appears not to be associated with prognosis following radical nephroureterectomy.

Purpose: Pretreatment measurements of systemic inflammatory response, including the Glasgow prognostic score (GPS), the neutrophil-to-lymphocyte ratio (NLR), the monocyte-to-lymphocyte ratio (MLR), the platelet-to-lymphocyte ratio (PLR) and the prognostic nutritional index (PNI) have been recognized as prognostic factors in clear cell renal cell carcinoma (CCRCC), but there is at present no study that compared these markers., Methods: We evaluated the pretreatment GPS, NLR, MLR, PLR and PNI in 430 patients, who underwent surgery for clinically localized CCRCC (pT1-3N0M0). Associations with disease-free survival were assessed with Cox models. Discrimination was measured with the C-index, and a decision curve analysis was used to evaluate the clinical net benefit., Results: On multivariable analyses, all measures of systemic inflammatory response were significant prognostic factors. The increase in discrimination compared with the stage, size, grade and necrosis (SSIGN) score alone was 5.8 % for the GPS, 1.1-1.4 % for the NLR, 2.9-3.4 % for the MLR, 2.0-3.3 % for the PLR and 1.4-3.0 % for the PNI. On the simultaneous multivariable analysis of all candidate measures, the final multivariable model contained the SSIGN score (HR 1.40, P < 0.001), the GPS (HR 2.32, P < 0.001) and the MLR (HR 5.78, P = 0.003) as significant variables. Adding both the GPS and the MLR increased the discrimination of the SSIGN score by 6.2 % and improved the clinical net benefit., Conclusions: In patients with clinically localized CCRCC, the GPS and the MLR appear to be the most relevant prognostic measures of systemic inflammatory response. They may be used as an adjunct for patient counseling, tailoring management and clinical trial design.

Purpose: To investigate the efficacy and technical applicability of cavitron ultrasonic surgical aspirator (CUSA)-driven zero-ischemia open partial nephrectomy in patients with renal tumors., Materials and Methods: We prospectively collected data of 13 consecutive patients, who underwent open partial nephrectomy under non-ischemic conditions. Tumor resection was done using an ultrasonic device (CUSA/SONOCA 300). Demographic and laboratory data, tumor characteristics, perioperative, and postoperative variables were evaluated., Results: The median age was 60.0 years (range 40-76); body mass index 28.0 kg/m(2) (range 22.9-43.3); tumor size 37.0 mm (range 11-110 mm). Patient were stratified according to the PADUA score into low- (score 6-7; n - 4), intermediate- (score 8-9; n - 5), and high-risk (score of >10; n - 4) groups, and the median score was 9.0 (range 6-13; SD +2.3). The vast majority of kidney tumors were diagnosed incidentally (n - 11; 84.6 %). Median operative time was 175 min (55-270 min); median time of tumor extirpation was 12 min (6-25 min); and median blood loss was 250 ml. Serum creatinine, glomerular filtration rate, and hemoglobin were nearly unaltered before and after surgery in 11 cases (84.6 %). Three patients received a blood transfusion (Clavien-Dindo Grade II); one had Grade IIIa complication (insertion of double J stent without general anesthesia); and three had Grade IIIb complications (insertion of double J under general anesthesia)., Conclusions: The ultrasonic device demonstrated acceptable hemostatic and resection properties during open partial nephrectomy without ischemia. Our series showed promising perioperative and postoperative outcomes that may help in maximizing preservation of renal function in partial nephrectomy candidates.