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In this study we evaluated outcomes of patients with metastatic renal cell carcinoma who received immunotherapy before surgery. We found that receiving immunotherapy combinations before surgery can offer patients benefits in reducing tumor size and improving disease control., Background: Immunotherapy (IO) has improved outcomes for patients with metastatic renal cell carcinoma (mRCC). However, the timing of surgical intervention for cytoreductive nephrectomy (CN) is still controversial for this group of patients., Patients and Methods: We identified patients with mRCC receiving IO-based therapies and undergoing CN. Patients were divided into 2 cohorts: those who underwent upfront CN and those who underwent deferred CN. Pathologic and radiographic features along with clinical outcomes were systematically collected. Comparisons were performed using Chi-square test, paired t-Test or Mann-Whitney-U test. Progression Free survival (PFS) and Overall Survival (OS) were estimated using the Kaplan-Meier method., Results: Fifty-one patients with mRCC were included, with a median follow-up of 21 months. 38 (74.5%) patients received IO-based therapies prior to CN, while 13 (25.5%) patients underwent up-front CN. IO-based therapies reduced median tumor size from pretreatment 10 cm to 8.6 cm post-treatment when given prior to CN. IO-TKI had a trend toward higher tumor shrinkage (-2.3 vs -1.2 cm). Pathologic T downstaging occurred in 42% (n=16) of patients, 11% (n=4) of whom had pT0 disease. Thrombus downstaging occurred in 13% (n=6) of patients, all with either partial response (PR) or complete response (CR) in metastases. PFS (HR=0.7, 95% CI 0.29-1.98, p=0.58) and OS (HR 0.4, 95% CI 0.13-1.57, p=0.21) were not statistically significant between 2 cohorts., Conclusions: IO-based therapies, particularly IO-TKIs, resulted in pathologic necrosis and reductions in tumor size prior to deferred CN. PFS and OS were similar for patients who received either upfront IO-based therapy or after CN., Competing Interests: Disclosure James Brugarolas: Advisory board/consultant: Eisai, Johnson and Johnson, Exelixis, Telix. ayal Kapur: Advisory board/consultant: ClearNano. Hans Hammers: Advisory board/consultant-ARMO Biosciences, Inc., Bayer AG, Bristol-Myers Squibb, Corvus Pharmaceuticals, Exelixis, Inc., Eli Lilly and Company, Merck & Co., Inc.,Pfizer, Inc., Novartis International AG, and Surface Oncology, Inc.; PI/research funding-Bristol-Myers Squibb and Merck & Co., Inc., ararvive,Surface Oncology,NGM Biopharmaceutical. Qian Qin: Advisory board/consultant – Exelixis. Solomon Woldu: Advisory Role/consultant: Urogen pharma. Yair Lotan: Advisory role/Consultant: Nanorobotics, Photocure, Astra Zeneca, Merck, Fergene, Abbvie, Nucleix, Ambu, Seattle Genetics, Hitachi, Ferring Research, verity pharmaceutics, virtuoso surgical, Stimit, Urogen, Vessi medical, CAPs medical, Xcures, BMS, Nonagen, Aura Biosciences, Inc., Convergent Genomics, Pacific Edge, Pfizer, Phinomics Inc, CG oncology, Uroviu, On target lab, Promis Diagnostics, Valar labs, Uroessentials. Jeffrey Cadeddu: Advisory Role/consultant: DeepQure, Distalmotion, Ownership: Levita Mganetics, EtiraRx, Onconanno. Tian Zhang: PI/research funding – Research support (to UTSW) from CPRIT, Merck, Janssen, Astra Zeneca, Pfizer, Astellas, Eli Lilly, Tempus, ALX Oncology, Janux Therapeutics, Exelixis, FBD Biologics, Guardant, OncoC4; Consulting/advisory relationships: Merck, Exelixis, Sanofi-Aventis, Janssen, Astra Zeneca, Pfizer, Amgen, BMS, Seagen, Eisai, Aveo, Eli Lilly, Bayer, Gilead, Novartis, EMD Serono, Aravive, MJH Associates, Vaniam, Aptitude Health, Peerview, eChinaHealth., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To evaluate factors associated with simple nephrectomy at a safety net hospital with a diverse patient population and large catchment area. Simple nephrectomy is an underreported surgery. Performance of simple nephrectomy may represent a failure of management of underlying causes., Methods: We performed a retrospective review of simple nephrectomies performed at a major urban safety net hospital from 2014 to 2019. Detailed demographic, surgical, and renal functional outcomes were abstracted. We assessed the medical and social factors leading to performance of simple nephrectomy and report contemporaneous perception of preventability of the simple nephrectomy by the surgeon., Results: Eighty-five patients underwent simple nephrectomy during the study period; 55% were non-white, 77% were women, and the median age at time of surgery was 46 years. The most common medical factors contributing to simple nephrectomy were stone disease in 55.3%, followed by retained ureteral stent (30.6%) and stricture (30.6%). The most common social factors were lack of insurance (58.5%), substance abuse issues (32.3%), mental health issues (24.6%), and immigration status (18.5%). In 38.8% of cases, the provider felt the surgery was preventable if medical factors leading to simple nephrectomy were properly addressed., Conclusions: Simple nephrectomy is a common surgery in the safety net hospital setting. Both medical and sociologic factors can lead to simple nephrectomy, and awareness of these factors can lead efforts to mitigate them. This review has led to the implementation of strategies to minimize occurrences of retained stents in our patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: Despite immune checkpoint inhibitor (ICI) approval for metastatic renal cell carcinoma (mRCC) in 2015, cytoreductive nephrectomy (CN) is guided by extrapolation from earlier classes of therapy. We evaluated survival outcomes, timing, and safety of combining CN with modern immunotherapy (IO) for mRCC., Methods: From 96,329 renal cancer cases reported to the NCDB between 2015 and 2016, we analyzed 391 surgical candidates diagnosed with clear cell mRCC treated with IO ± CN and no other systemic therapies. Primary outcome was overall survival (OS) stratified by the performance of CN (CN + IO vs. IO alone). Secondary outcomes included OS stratified by the timing of CN, pathologic findings, and perioperative outcomes., Results: Of 391 patients, 221 (56.5%) received CN + IO and 170 (43.5%) received IO only. Across a median follow-up of 14.7 months, patients who underwent CN + IO had superior OS (median NR vs. 11.6 months; hazard ratio 0.23, P < 0.001), which was upheld on multivariable analyses. IO before CN resulted in lower pT stage, grade, tumor size, and lymphovascular invasion rates compared to upfront CN. Two of 20 patients (10%) undergoing CN post-IO achieved complete pathologic response in the primary tumor (pT0). There were no positive surgical margins, 30-day readmissions, or prolonged length of stay in patients undergoing delayed CN., Conclusion: Using a large, national, registry-based cohort, we provide the first report of survival outcomes in mRCC patients treated with CN combined with modern IO. Our findings support an oncologic role for CN in the ICI era and provide preliminary evidence regarding the timing and safety of CN relative to IO administration., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Radical nephrectomy with inferior vena cava thrombectomy (RN-IVCT) is a complicated procedure for which the impact of hospital case volume on overall survival (OS) is unknown., Objective: To assess the degree to which renal cell carcinoma (RCC) with inferior vena cava tumor thrombus (IVC-TT) care is centralized and to evaluate the impact of hospital case volume on outcomes following RN-IVCT., Design, Setting, and Participants: The National Cancer Data Base was queried for patients with pT3b-c RCC treated with RN-IVCT. Hospitals were classified by case volume percentile as low (<75th percentile, <0.67 cases annually), intermediate (75th-95th percentile, 0.67-2.99 cases annually), or high (>95th percentile, >3 cases annually)., Outcome Measurements and Statistical Analysis: The primary outcome was OS. Secondary outcomes were short-term (30- and 90-d) mortality rates according to hospital case volume. Kaplan-Meier curves and Cox regression model were used to evaluate OS and the effect of covariables., Results and Limitations: There were 2664 cases of RN-IVCT for pT3b-c tumors reported by 573 institutions, of which 435, 108, and 30 were classified as low, intermediate, and high volume, accounting for 28.5%, 34.5%, and 37% of cases, respectively. Treatment at high-volume institutions was associated with better OS: the median OS was 42, 53, and 60 months for low, intermediate and high-volume centers, respectively (p=0.009). After multivariable adjustment, treatment at a high-volume institution was associated with a 24% relative risk reduction for all-cause mortality compared to treatment at a low-volume institution (hazard ratio 0.76, 95% confidence interval 0.65-0.89; p=0.001). There was no significant difference in short-term mortality following RN-IVCT when stratified by hospital case volume., Conclusions: Higher hospital case volume was associated with longer OS for patients undergoing RN-IVCT. These findings support efforts to centralize care for cases of advanced RCC., Patient Summary: In this study we looked at the impact of hospital case volume on survival following surgery for renal cell carcinoma and inferior vena cava thrombectomy. Survival was significantly better in high-volume hospitals performing three or more procedures per year., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: A prospective study of partial vs. radical nephrectomy demonstrated worse overall survival in patients undergoing partial nephrectomy which appeared to be driven by cardiovascular outcomes. We sought to determine if the blood pressures or use of antihypertensive medications differed between patients who underwent partial or radical nephrectomy., Materials and Methods: A tertiary-referral institutional renal mass database was queried for patients between 2006 and 2012 undergoing partial or radical nephrectomy. Serial blood pressure follow-up, clinicopathologic variables, and changes in medications were collected. Patients were excluded for inadequate data, noncurative-intent surgery, noncancer surgical indication, and absence of medication information. Time-dependent hemodynamic changes were compared by split-plot analysis of variance and addition to antihypertensive regimen was studied as time-to-event survival analyses with Kaplan-Meier curves and a Cox proportional hazards model., Results: A final cohort of 264 partial nephrectomy and 130 radical nephrectomy cases were identified. Patients undergoing partial nephrectomy were younger, more likely to have T1 tumors, and had lower preoperative creatinine (P<0.001 for all). No differences were noted on postoperative hemodynamics (P>0.05). Significantly more patients who underwent partial nephrectomy added antihypertensive medications postoperatively (P≤0.001) and surgical treatment remained as a significant independent predictor on Cox regression (hazard ratio = 2.51, P = 0.002). Limitations include the retrospective nature of the study and potential for unidentified confounders., Conclusion: Hemodynamic parameters after radical or partial nephrectomy may be different. The etiology of this observation, is currently unexplored. Additional prospective mechanistic investigations are warranted., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To improve risk stratification for recurrence prognostication in patients with localised clear cell renal cell carcinoma (ccRCC)., Patients and Methods: In all, 367 patients with non-metastatic ccRCC were included. The cohort was divided into a training and validation set. Using tissue microarrays, immunostaining was performed for 24 biomarkers representative of key pathways in ccRCC. Using Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression, we identified several markers that were used to construct a risk classifier for risk of disease recurrence., Results: The median (interquartile range) follow-up was 63.5 (24.0-85.3) months. Five out of 24 markers were selected by LASSO Cox regression for the risk classifier: N-cadherin, E-cadherin, Ki67, cyclin D1 and phosphorylated eukaryotic initiation factor 4E binding protein-1 (p-4EBP1). Patients were classified as either low, intermediate or high risk of disease recurrence by tertiles of risk score. The 5-year recurrence-free survival (RFS) was 93.8%, 87.7% and 70% for patients with low-, intermediate- and high-risk scores, respectively (P < 0.001). Patients with a high marker score had worse RFS on multivariate analysis adjusted for age, gender, race and the Mayo Clinic Stage, Size, Grade, and Necrosis (SSIGN) score (hazard ratio 3.66, 95% confidence interval 1.58-8.49, P = 0.003 for high vs low marker score in the overall cohort). The five-marker classifier increased the concordance index of the clinical model in both the training and validation sets., Conclusion: We developed a five-marker-based prognostic tool that can effectively classify patients with ccRCC according to risk of disease recurrence after surgery. This tool, if prospectively validated, could provide individualised risk estimation for patients with ccRCC., (© 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.)

Objective: To compare changes in renal function after radical nephrectomy for renal cell carcinoma (RCC) and radical nephroureterectomy for upper tract urothelial carcinoma (UTUC), and assess their effects on non-cancer-specific mortality (CSM)., Methods: Clinicopathologic data from 1114 patients with RCC or UTUC treated surgically from 1997 to 2013 were compiled. Patients who underwent nephron-sparing surgeries, had bilateral disease, received chemotherapy, or had <1 month of follow-up were excluded. Renal function (estimated glomerular filtration rate [eGFR]) was calculated preoperatively, 3 months postoperatively, and at last follow-up. Events were defined as ≥25% decline in eGFR from baseline. Event-free survival and non-CSM were assessed using Kaplan-Meier analysis. Multivariable Cox regression was performed to identify predictors of events., Results: Four hundred thirty-five patients were included (317 radical nephrectomy, 118 radical nephroureterectomy). Median follow-up was 38.2 months. UTUC patients were older (P < .001), had worse Charlson score (P < .001), and more frequently used tobacco (P = .006). Median baseline eGFR was lower in UTUC patients (58.4 vs 74.9, P < .001). RCC patients experienced a larger event rate following surgery at first (56.8% vs 31.4%, P < .001) and last (51.7% vs 35.6%, P = .003) follow-up than UTUC patients. On Kaplan-Meier analysis, UTUC patients exhibited worse non-CSM (P < .001). Postsurgical decline in renal function was a significant predictor of non-CSM in RCC patients at first (hazard ratio = 4.71, P = .041) and last (hazard ratio = 4.56, P = .018) follow-up, whereas this was not the case for UTUC patients., Conclusion: UTUC patients had worse baseline eGFR and overall health status than RCC patients. RCC patients experienced greater postsurgical declines in renal function. These results shed light on differences in patient characteristics between these forms of kidney cancer and guide expectations for postoperative renal function., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: To compare renal function changes after radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC) based on the presence of preoperative hydronephrosis., Materials and Methods: Clinicopathologic data of 208 patients with UTUC treated surgically from 1998 to 2013 were compiled. Patients with bilateral disease, less than 1 month follow up, missing hydronephrosis data, or who underwent nephron-sparing approaches were excluded. Estimated glomerular filtration rate (eGFR) was calculated preoperatively, at first follow up (within 3 months) and at last follow up using the Modification of Diet in Renal Disease equation. Events were defined as new-onset stage III chronic kidney disease (CKD) or worsening of CKD stage in preexisting CKD. Kaplan-Meier event-free survival was assessed. Cox regression was performed to identify predictors of events., Results: A total of 132 patients were analyzed, including 62 (47.0%) with hydronephrosis. Median follow up was 28.6 months. Patients with hydronephrosis had larger tumors (p = 0.045) and higher pathologic stage (p = 0.010) than those without hydronephrosis. Baseline eGFR was comparable between groups (p = 0.088). Patients without hydronephrosis experienced greater declines in eGFR following surgery (p < 0.001) and higher event rates at first (42.8% versus 24.2%, p = 0.028) and last (54.2% versus 30.6%, p = 0.008) follow up. On Cox regression, hydronephrosis predicted lower event likelihood in the long term (univariate HR 0.54, p = 0.033), while ureteral tumor location predicted lower event likelihood in the short term (HR 0.52, p = 0.030)., Conclusions: Patients with hydronephrosis undergoing RNU for UTUC experience less decline in renal function than those without hydronephrosis. Given the prevalence of renal dysfunction in patients with UTUC, our results may help inform preoperative counseling.

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: The overall incidence of pulmonary metastasis of T1 renal cell carcinoma is low. We evaluated the usefulness of chest x-rays based on the current AUA (American Urological Association) guidelines and NCCN Guidelines® for T1a renal cell carcinoma surveillance., Materials and Methods: Between 2006 and 2012, 258 patients with T1a renal cell carcinoma were treated with partial nephrectomy, radical nephrectomy or radio frequency ablation with surveillance followup at our institution. A retrospective chart review was performed to identify demographics, pathological findings and surveillance records. The primary outcome was the incidence of asymptomatic pulmonary recurrences diagnosed by chest x-ray in cases of T1a disease. Our secondary outcome was a comparison of diagnoses by treatment modality (partial nephrectomy, radical nephrectomy or radio frequency ablation)., Results: Pulmonary metastases developed in 3 of 258 patients (1.2%) but only 1 (0.4%) was diagnosed by standard chest x-ray surveillance. Median followup in the entire cohort was 36 months (range 6 to 152) and 193 of 258 patients (75%) had greater than 24 months of followup. A mean of 3.3 surveillance chest x-rays were completed per patient. When assessed by treatment type, there was no significant difference in the recurrence rate for partial nephrectomy (0 of 191 cases), radical nephrectomy (0 of 22) or radio frequency ablation (1 of 45 or 2.2%) (p = 0.09)., Conclusions: Chest x-rays are a low yield diagnostic tool for detecting pulmonary metastasis in patients treated for T1a renal cel carcinoma. Treatment mode does not appear to influence the need for chest x-ray surveillance., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the prognostic significance of Forkhead Box A1 (FOXA1) expression in patients with upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU)., Materials and Methods: A retrospective analysis of 566 patients undergoing RNU at seven academic medical centers was performed. Tissue microarrays were subjected to immunohistochemistry using a commercially available polyclonal FOXA1 antibody. Logistic regression determined the association of FOXA1 expression with pathologic features and survival outcomes., Results: Three hundred twenty-two men and 244 women were included. The pathologic distribution of specimens included 53% muscle-invasive or greater (≥pT2), 74% high-grade, 16% with flat architecture, 13% with necrosis, 21% with lymphovascular invasion, 18% with concomitant carcinoma in situ, and 8% with positive lymph nodes. The median FOXA1 score was 5.0 (range: 0-8). Lower FOXA1 expression was significantly correlated with advanced pathologic stage (≥pT3) (P = .02), concomitant carcinoma in situ (P = .006), and renal pelvis (vs ureter) location (P < .0001). At a median follow-up of 27.0 months (range: 3-196), 139 patients (25%) experienced disease recurrence and 121 (21%) died from the disease. In a multivariate model, lower FOXA1 expression was independently associated with disease recurrence (hazard ratio [HR]: 1.11, 95% confidence interval [CI]: 1.05-1.62, P = .04), cancer-specific mortality (HR: 1.17, 95% CI: 1.03-1.92, P = .04), and all-cause mortality (HR: 1.08, 95% CI: 1.02-1.18, P = .05)., Conclusion: Lower FOXA1 expression is associated with adverse pathologic features and inferior survival outcomes for UTUC patients undergoing RNU. These data indicate lower FOXA1 expression may be a marker of aggressive disease in UTUC., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: We created a prognostic tool for the prediction of oncologic outcomes after radical nephroureterectomy (RNU) for high-grade non-metastatic upper tract urothelial carcinoma (UTUC)., Methods: UTUC collaboration was utilized to include 586 patients who underwent RNU for non-metastatic high-grade UTUC. Survival outcomes were compared according to a score defined based on the sum of the independent prognostic variables., Results: The study included 382 males with a median age 70 years (range 28-97). Independent prognostic factors included: T (t stage), A (architecture), LVI (lympho-vascular invasion) and L (lymphadenectomy). TALL score (1-7) was the sum of T (≤T1 = 1, T2 = 2, T3 = 3 and T4 = 4), A (papillary = 0 and sessile = 1), LVI (absent = 0 and present = 1) and L (lymphadenectomy = 0 and no lymphadenectomy = 1). Five-year disease-free survival (DFS) and cancer-specific survival (CSS) were stratified into four risk categories according to the TALL score: low (TALL 0-2; 86 % DFS and 90 % CSS), intermediate (TALL = 3; 71 % DFS and 75 % CSS), high (TALL = 4; 57 % DFS and 58 % CSS) and very high risk (TALL ≥ 5; 34 % DFS and 38 % CSS) using Kaplan-Meier survival analyses. TALL score was externally validated in a single-center cohort of 85 UTUC patients., Conclusions: We developed a multivariable prognostic tool for the prediction of oncological outcomes after RNU for high-grade UTUC. The score can be used for patient counseling, selection for adjuvant systemic therapies and design of clinical trials.

Purpose: To compare renal function outcomes in patients undergoing radical nephroureterectomy (RNU) or partial (distal) ureterectomy (PU) for upper tract urothelial carcinoma (UTUC)., Methods: Clinicopathologic data of patients undergoing RNU or PU for UTUC from 1998 to 2012 were compiled. Glomerular filtration rate was calculated preoperatively and postoperatively using the Modification of Diet in Renal Disease equation. We defined "event" as new-onset stage III chronic kidney disease (CKD) or worsening of CKD stage with preexisting CKD. Event-free survival was assessed with Kaplan-Meier methods. Cox regression analyses were performed to identify predictors of events., Results: In total, 193 patients underwent RNU (n = 143) or PU (n = 50) over a median follow-up of 25.9 months. Overall, 15% of patients died of UTUC. High tumor grade (85.9% vs. 66.0%, P = 0.003) and locally advanced stage (>pT2, 37.8% vs. 18.0%, P = 0.014) were significantly more frequent in the RNU cohort. Stage III or higher CKD was present in 61% of RNU patients vs. 48% of PU patients (P = 0.135) at baseline. Although total event rate was higher in the PU cohort (66% vs. 43.4%, P = 0.008), event rates within the first 3 months of surgery were similar between the groups (P = 0.572). Adjuvant chemotherapy was the only predictor of events on Cox regression., Conclusions: Rates of new-onset CKD or worsening of CKD stage were similar in patients treated with RNU and PU. Adjuvant chemotherapy may have a more significant effect on renal outcomes than surgical approach, warranting further investigation. Consideration should be given to preoperative chemotherapy, as adjuvant chemotherapy is limited by decreased renal function following surgery., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Conditional survival (CS) provides better estimates of the survival probability at each follow-up time, and its usefulness has been proven in several solid malignancies., Objective: To assess the changes in 5-yr CS rates after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) and to determine how well-established prognostic factors evolve over time., Design, Setting, and Participants: We analysed data from 3544 patients treated with RNU at 15 international academic centres between 1989 and 2012., Intervention: RNU., Outcomes Measurements and Statistical Analysis: Conditional intravesical recurrence-free (IVRFS), cancer-specific survival (CSS), and overall survival (OS) estimates were calculated using the Kaplan-Meier method. A multivariable Cox regression model was used to calculate proportional hazard ratios for the prediction of mortality., Results and Limitations: The 5-yr bladder cancer recurrence-free survival, CSS, and OS rates were 54.9%, 72.2%, and 62.6%, respectively. Given a 1-, 2-, 3-, and 4-yr survivorship, the 5-yr conditional OS rates improved to 65.2%, 69.3%, 71.5%, and 73.0%, respectively. The 5-yr CS improvement was primarily noted among surviving patients with advanced-stage disease. The impact of pathologic parameters on CS estimates decreased over time for both CSS and OS, whereas the impact of age and gender increased with survivorship. No survival benefit was noted regarding the adjuvant chemotherapy status. Findings were confirmed upon multivariable analyses. Tumour location, the presence of carcinoma in situ, and the type of bladder cuff excision were continuously predictive for IVRFS whatever the survivorship. A limitation is the retrospective design., Conclusions: CS analysis demonstrates that the patient risk profile evolves during the post-RNU follow-up. The probability of survival markedly increases over time in patients having high-stage disease. The impact of prognostic pathologic features decreases over time and can disappear for long-term CS., Patient Summary: In this study, we found that the risk of intravesical recurrence, cancer-specific survival, and overall mortality evolves over the follow-up after surgery. Taking into account the survivorship provides better estimates of the survival probability at each follow-up time., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: To test the hypothesis that perioperative blood transfusion (PBT)impacts oncologic outcomes of patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC)., Methods: Retrospective analysis of 2492 patients with UTUC treated at 23 institutions with RNU between 1987 and 2007.Cox regression models addressed the association of PBT with disease recurrence, cancer-specific mortality and any-cause mortality., Results: A total of 510 patients (20.5%) patients received PBT. Within a median follow-up of 36 months (Interquartile range: 55 months), 663 (26.6%) patients experienced disease recurrence, 545 patients (21.9%) died of UTUC and 884 (35.5%) patients died from any cause. Patients who received PBT were at significantly higher risk of disease recurrence, cancer-specific mortality and overall mortality than patients not receiving PBT in univariable Cox regression analyses. In multivariable Cox regression analyses that adjusted for the effects of standard clinicopathologic features, PBT did not remain associated with disease recurrence (HR: 1.11; 95% CI 0.92-1.33, p = 0.25), cancer-specific mortality (HR: 1.09; 95% CI 0.89-1.33, p = 0.41) or overall mortality (HR: 1.09; 95% CI 0.93-1.28, p = 0.29)., Conclusions: In patients undergoing RNU for UTUC, PBT is associated with disease recurrence, cancer-specific survival or overall survival in univariable, but not in multivariable Cox regression analyses., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Intravesical recurrence after radical nephroureterectomy (RNU) is a frequent event requiring intense cystoscopic surveillance. Recently, a prospective randomized clinical trial has shown that a single intravesical postoperative dose of mitomycin C (MMC) reduces the absolute risk of intravesical recurrence after RNU., Objective: The aim of the current study was to identify predictors of intravesical recurrence and to develop a tool to allow a risk-stratified approach supporting patient counseling for cystoscopic surveillance and postoperative intravesical MMC administration., Design, Setting, and Participants: We performed a retrospective analysis of 1839 patients with upper tract urothelial carcinoma (UTUC). The data set was split into a development cohort of 1261 patients from North America and a validation cohort of 578 patients from Europe., Interventions: RNU with bladder cuff excision was performed. The surgical approach was open in 1424 patients (77.4%) and laparoscopic in 415 patients (22.6%)., Outcome Measurements and Statistical Analyses: Univariable and multivariable Cox regression models addressed time to intravesical recurrence after RNU. We developed a nomogram for prediction of the probability of intravesical recurrence at 3, 6, 9, 12, 18, 24, and 36 mo. Predictive accuracy was quantified using the concordance index. Decision curve analysis was performed to evaluate the clinical benefit associated with the use of our nomograms., Results and Limitations: With a median follow-up of 45 mo, intravesical recurrence occurred in 577 patients (31%). The probability of intravesical recurrence-free survival at 6, 12, 24, and 36 mo was 85% ± 1%, 78% ± 1%, 68% ± 1%, and 47% ± 2%, respectively. In multivariable Cox regression analysis, advanced age, male gender, ureteral tumor location, laparoscopic surgical technique, endoscopic distal ureteral management, previous bladder cancer, higher tumor stage, concomitant carcinoma in situ, and lymph node involvement were all significantly associated with intravesical recurrence (p values ≤ 0.04). The nomograms were highly accurate for predicting intravesical recurrence in the external validation cohort (concordance index of 67.8% and 69.0% for the reduced model and the full model, respectively), and calibration plots revealed only minor overestimation beyond 24 mo. If one decided to perform postoperative instillation based on the risk of intravesical recurrence of 15% at 24 mo, one would spare 23% of the patients while not preventing only 0.3% of intravesical recurrences. The lack of information on the stage and grade of the intravesical recurrences is the main limitation of the study., Conclusions: Intravesical recurrence after RNU is a common event in patients with UTUC. We developed nomograms that predict intravesical recurrence after RNU with reasonable accuracy. Such nomograms could improve the clinical decision-making process with regard to cystoscopic surveillance scheduling and postoperative intravesical instillations of MMC after RNU., (Copyright © 2013. Published by Elsevier B.V.)

Background: There is a lack of consensus regarding the optimal approach to the bladder cuff during radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC)., Objectives: To compare the oncologic outcomes following RNU using three different methods of bladder cuff management., Design, Setting, and Participants: Retrospective analysis of 2681 patients treated with RNU for UTUC at 24 international institutions from 1987 to 2007., Intervention: Three methods of bladder cuff excision were performed: transvesical, extravesical, and endoscopic., Outcome Measurements and Statistical Analysis: Univariable and multivariable models tested the effect of distal ureter management on intravesical recurrence, recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS)., Results and Limitations: Of the 2681 patients, 1811 (67.5%) underwent the transvesical approach; 785 (29.3%), the extravesical approach; and 85 (3.2%), the endoscopic approach. There was no difference in terms of RFS, CSS, and OS among the three distal ureteral management approaches. Patients who underwent the endoscopic approach were at significantly higher risk of intravesical recurrence compared with those who underwent the transvesical (p=0.02) or extravesical approaches (p=0.02); the latter two groups did not differ from each other (p=0.40). Actuarial intravesical RFS estimates at 2 and 5 yr after RNU were 69% and 58%, 69% and 51%, and 61% and 42% for the transvesical, extravesical, and endoscopic approaches, respectively. In multivariate analyses, distal ureteral management (p=0.01), surgical technique (open vs laparoscopic; p=0.02), previous bladder cancer (p<0.001), higher tumor stage (trend; p=0.01), concomitant carcinoma in situ (CIS) (p<0.001), and lymph node involvement (trend; p<0.001) were all associated with intravesical recurrence. Excluding patients with history of previous bladder cancer, all variables remained independent predictors of intravesical recurrence., Conclusions: The endoscopic approach was associated with higher intravesical recurrence rates. Interestingly, concomitant CIS in the upper tract is a strong predictor of intravesical recurrence after RNU. The association of laparoscopic RNU with intravesical recurrence needs to be further investigated., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate the effect of distal ureter management on oncological outcomes in patients with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma., Methods and Materials: Retrospective review of patient records and operative reports was conducted on 122 patients who underwent RNU. Data were compared between 2 groups using substratification by distal ureter management (transvesical bladder cuff [TVBC]) vs. no TVBC)., Results: Mean patient age was 69.0 years and 63.1% were male. Median follow-up was 32.0 months. Most patients (n = 76, 62.3%) received a TVBC and 46 (37.7%) patients received no TVBC during RNU. There were no significant differences in clinicopathological variables between both groups except for a higher rate of lymphadenectomy during surgery in the TVBC group (38.2% vs. 15.2%). On multivariate analysis, intravesical recurrence (IVR) was not affected by distal ureter management but was affected by tumor multifocality (hazard ratio [HR] = 2.2; 95% confidence interval [CI], 1.2-4.0; P = 0.013). However, non-IVR-free survival (non-IVR FS) and cancer-specific survival (CSS) were independently influenced by T stage (HR = 4.9; 95% CI, 1.5-16.3; P = 0.010 for non-IVR FS and HR = 6.3; 95% CI, 1.7-23.1; P = 0.005 for CSS) and management of the distal ureter (HR = 3.2; 95% CI, 1.3-7.6; P = 0.010 for non-IVR FS and HR = 3.4; 95% CI, 1.3-8.8; P = 0.010 for CSS)., Conclusions: In our study, surgical management of the distal ureter without excision of a TVBC resulted in significantly worse non-IVR FS and CSS but had no influence on IVR. This is hypothesis generating and supports further prospective study as to standardization of BC resection during RNU., (© 2013 Published by Elsevier Inc.)

Objective: To evaluate a nomogram using the RENAL Nephrometry Score (RENAL-NS) that was developed to characterize masses as benign vs. malignant and high vs. low grade in our patients with small renal masses treated with partial nephrectomy (PN). The nomogram was previously developed and validated in patients with widely variable tumor sizes., Materials and Methods: Retrospective review of PN performed between 1/2003 and 7/2011. Imaging was reviewed by a urologic surgeon for RENAL-NS. Final pathology was used to classify tumors as benign or malignant and low (I/II) or high (III/IV) Fuhrman grade. Patient age, gender, and RENAL score were entered into the nomogram described by Kutikov et al. to determine probabilities of cancer and high-grade disease. Area under the curve was determined to assess agreement between observed and expected outcomes for prediction of benign vs. malignant disease and for prediction of high- vs. low-grade or benign disease., Results: A total of 250 patients with 252 masses underwent PN during the study period; 179/250 (71.6%) had preoperative imaging available. RENAL-NS was assigned to 181 masses. Twenty-two percent of tumors were benign. Eighteen percent of tumors were high grade. Area under the curve was 0.648 for predicting benign vs. malignant disease and 0.955 for predicting low-grade or benign vs. high-grade disease., Conclusions: The RENAL-NS score nomogram by Kutikov does not discriminate well between benign and malignant disease for small renal masses. The nomogram may potentially be useful in identifying high-grade tumors. Further validation is required where the nomogram probability and final pathologic specimen are available., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Aims: Evidence suggests a detrimental effect of diabetes mellitus (DM) on cancer incidence and outcomes. To date, the effect of DM and its treatment on prognosis in upper tract urothelial carcinoma (UTUC) remains uninvestigated. We tested the hypothesis that DM and metformin use impact oncologic outcomes of patients treated with radical nephroureterectomy (RNU) for UTUC., Methods: Retrospective analysis of 2492 patients with UTUC treated at 23 institutions with RNU without neoadjuvant therapy. Cox regression models addressed the association of DM and metformin use with disease recurrence, cancer-specific mortality and any-cause mortality., Results: A total of 365 (14.3%) patients had DM and 194 (7.8%) patients used metformin. Within a median follow-up of 36 months, 663 (26.6%) patients experienced disease recurrence, 545 patients (21.9%) died of UTUC and 884 (35.5%) patients died from any cause. Diabetic patients who did not use metformin were at significantly higher risk of disease recurrence and cancer-specific death compared to non-diabetic patients and diabetic patients who used metformin. In multivariable Cox regression analyses, DM treated without metformin was associated with worse recurrence-free survival (HR: 1.44, 95% CI 1.10-1.90, p = 0.009) and cancer-specific mortality (HR: 1.49, 95% CI 1.11-2.00, p = 0.008)., Conclusions: Diabetic UTUC patients without metformin use have significantly worse oncologic outcomes than diabetics who used metformin and non-diabetics. The possible mechanism behind the impact of DM on UTUC biology and the potentially protective effect of metformin need further elucidation., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Purpose: To report the outcomes of patients with pathologic T4 UTUC and investigate the potential impact of peri-operative chemotherapy combined with radical nephroureterectomy (RNU) and regional lymph node dissection (LND) on oncologic outcomes., Materials and Methods: Patients with pathologic T4 UTUC were identified from the cohort of 1464 patients treated with RNU at 13 academic centers between 1987 and 2007. Oncologic outcomes were stratified according to utilization of perioperative systemic chemotherapy and regional LND as an adjunct to RNU., Results: The study included 69 patients, 42 males (61%) with median age 73 (range 43-98). Median follow-up was 17 months (range: 6-88). Lymphovascular invasion was found in 47 (68%) and regional lymph node metastases were found in 31 (45%). Peri-operative chemotherapy was utilized in 29 (42%) patients. Patients treated with peri-operative chemotherapy and RNU with LND demonstrated superior oncologic outcomes compared to those not treated by chemotherapy and/or LND during RNU (3Y-DFS: 35% vs. 10%; P = 0.02 and 3Y-CSS: 28% vs. 14%; P = 0.08). In multivariate Cox regression analysis, administration of peri-operative chemotherapy and utilization of LND during RNU was associated with lower probability of recurrence (HR: 0.4, P = 0.01), and cancer specific mortality (HR: 0.5, P = 0.06)., Conclusions: Pathological T4 UTUC is associated with poor prognosis. Peri-operative chemotherapy combined with aggressive surgery, including lymph node dissection, may improve oncological outcomes. Our findings support the use of aggressive multimodal treatment in patients with advanced UTUC.

Objective: To evaluate the gender-specific differential effects of smoking habits and cumulative smoking exposure on outcomes in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU)., Patients and Methods: A total of 864 consecutive patients, comprising 553 (64%) men and 311 (36%) women, from five international institutions underwent RNU without neoadjuvant chemotherapy. Smoking history included smoking status (current, former or never), quantity of cigarettes per day (CPD), smoking duration in years and years since smoking cessation. Cumulative smoking exposure was categorized as light short-term (≤19 CPD and ≤19.9 years), moderate (all combinations except light short-term and heavy long-term), and heavy long-term (≥20 CPD and ≥20 years). Uni- and multivariable competing risk regression models were used to assess the associations with outcomes., Results: Overall, 244 (28.2%), 297 (34.4%) and 323 (37.4%) patients were never, former and current smokers, respectively. There were no differences in smoking status, quantity and duration between the genders. In female ever smokers, 30 (9.6%), 121 (38.9%) and 67 (21.5%) were light short-term, moderate and heavy long-term smokers, respectively. Compared with men, female current smokers were more likely to experience disease recurrence in univariable analysis (P = 0.013). In heavy long-term smokers, female gender was significantly associated with disease recurrence (hazard ratio [HR] 1.7; P = 0.03) and cancer-specific mortality (HR 2.0; P = 0.009) in multivariable analysis that adjusted for standard clinico-pathological features. In female patients only, smoking quantity, duration and cumulative exposure were associated with disease recurrence and cancer-specific mortality on multivariable analyses (P ≤ 0.025)., Conclusions: The impact of smoking on UTUC outcomes after RNU is gender-specific. Females who are current and heavy long-term smokers experience worse outcomes than their male counterparts. Further research is needed to elucidate the molecular mechanisms underlying the gender-specific differential effect of smoking on UTUC outcomes., (© 2013 BJU International.)

Unlabelled: What's known on the subject? and what does the study add?: Radical nephroureterectomy (RNU), the standard of care treatment for high-risk urothelial carcinoma of the upper tract (UTUC), results in loss of a renal unit. Loss of renal function decreases eligibility for systemic chemotherapies and results in decreased overall survival in various malignancies. The study shows that only a small proportion of patients had a preoperative renal function that would allow cisplatin-based chemotherapy. Moreover, eGFR significantly decreased after RNU, thereby lowering the rate of cisplatin eligibility to only 16 and 52% of patients based on the thresholds of 60 and 45 mL/min/1.73 m(2) , respectively. Taken together with the rest of the literature, the findings of the study support the use of cisplatin-based chemotherapy, when indicated, in the neoadjuvant rather than adjuvant setting., Objective: To report (i) the estimated glomerular filtration rate (eGFR) changes in patients undergoing radical nephro-ureterectomy (RNU) for upper tract urothelial carcinoma (UTUC); (ii) the rate of change in eGFR in patients eligible for cisplatin-based chemotherapy; and (iii) the association of preoperative, postoperative and rate of change of renal function variables with survival outcomes., Patient and Methods: We performed a retrospective analysis of 666 patients treated with RNU for UTUC at seven international institutions from 1994 to 2007. The eGFR was calculated at baseline and at 3-6 months (Modification of Diet in Renal Disease formula (MDRD) and Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EP) equations)., Results: The median (interquartile range) eGFR decreased by 18.2 (8-12)% after RNU. A total of 37% of patients had a preoperative eGFR ≥ 60 mL/min/1.73 m(2) , which decreased to 16% after RNU (P < 0.001); 72% of patients had a preoperative eGFR ≥ 45 mL/min/1.73 m(2) , which decreased to 52% after RNU (P < 0.001). The distributions were similar when analyses were restricted to patients with locally advanced disease (pT3-pT4) and/or lymph node metastasis. Patients older than the median age of 70 years were more likely to have a decrease in eGFR after RNU (P < 0.001). None of the renal function variables was associated with clinical outcomes such as disease recurrence, cancer-specific and overall mortality; however, when analyses were restricted to patients who had no adjuvant chemotherapy and did not experience disease recurrence (n = 431), a preoperative eGFR ≥ 60 mL/min/1.73 m(2) (P = 0.03) and a postoperative eGFR ≥ 45 mL/min/1.73 m(2) (P = 0.04) were associated with better overall survival in univariable analyses., Conclusions: In patients who had UTUC, eGFR was low and furthermore, it significantly decreased after RNU. Renal function did not affect cancer-specific outcomes after RNU., (© 2013 BJU International.)

Purpose: We conceived and proposed a unique and optimized nomogram to predict cancer specific survival after radical nephroureterectomy in patients with upper tract urothelial carcinoma by merging the 2 largest multicenter data sets reported in this population., Materials and Methods: The international and the French national collaborative groups on upper tract urothelial carcinoma pooled data on 3,387 patients treated with radical nephroureterectomy for whom full data for nomogram development were available. The merged study population was randomly split into the development cohort (2,371) and the external validation cohort (1,016). Cox regressions were used for univariable and multivariable analyses, and to build different models. The ultimate reduced nomogram was assessed using Harrell's concordance index (c-index) and decision curve analysis., Results: Of the 2,371 patients in the nomogram development cohort 510 (21.5%) died of upper tract urothelial carcinoma during followup. The actuarial cancer specific survival probability at 5 years was 73.7% (95% CI 71.9-75.6). Decision curve analysis revealed that the use of the best model was associated with benefit gains relative to the prediction of cancer specific survival. The optimized nomogram included only 5 variables associated with cancer specific survival on multivariable analysis, those of age (p = 0.001), T stage (p <0.001), N stage (p = 0.001), architecture (p = 0.02) and lymphovascular invasion (p = 0.001). The discriminative accuracy of the nomogram was 0.8 (95% CI 0.77-0.86)., Conclusions: Using standard pathological features obtained from the largest data set of upper tract urothelial carcinomas worldwide, we devised and validated an accurate and ultimate nomogram, superior to any single clinical variable, for predicting cancer specific survival after radical nephroureterectomy., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To compare oncologic outcomes in an international cohort of patients who underwent either partial ureterectomy (PU) or radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC)., Methods: A subgroup of patients from the UTUC Collaboration with operation classified as PU or RNU was used (n = 835). Clinicopathologic outcomes were evaluated. Survival was assessed using the Kaplan-Meier method. Cox regression addressed recurrence-free survival (RFS) and cancer-specific survival (CSS)., Results: Median age and follow-up were 69 years (range 32-97 years) and 34 months (range 1-246 months), respectively. Relapse occurred in 28.5% of patients (19.6% local, 8.9% systemic). At analysis, 180 patients (21.6%) died of UTUC. Eighty-one patients (9.7%) underwent PU and 754 (90.3%) underwent RNU. High tumor grade (77.3% vs 55.6%, P <.001) and advanced T stage (>T1, 41.7% vs 30.9%, P <.001) were significantly more common in the RNU cohort. Significantly more patients in the PU group received adjuvant chemotherapy than the RNU arm (25.9% vs 16.8%, respectively, P = .05). Kaplan-Meier median 5-year survival probabilities for RFS (69.4% vs 75.9%, P = .06) and CSS (67.5% vs 72.1%, P = .06) were not significantly different between PU and RNU. On multivariable analysis, Eastern Cooperative Oncology Group (ECOG) performance status, tumor stage, tumor necrosis, and lymph node (LN) status were significantly associated with CSS., Conclusion: In patients with UTUC, PU seems to provide oncologic efficacy equal to RNU. Ability to maximize global renal function with utilization of PU is an attractive strategy in carefully selected patients., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: The role of lymph node dissection is still controversial in patients treated with radical nephroureterectomy for upper tract urothelial cancer. We developed a pathological nodal staging model that allows quantification of the likelihood that a patient with pathologically node negative disease has, indeed, no lymph node metastasis., Materials and Methods: We analyzed data on 814 patients treated with radical nephroureterectomy and lymph node dissection, and estimated the sensitivity of pathological nodal staging using a β-binomial model. We developed a pathological nodal staging score that represents the probability that a case is correctly staged as node negative., Results: A median of 5 lymph nodes (range 1 to 46) was removed and 593 patients (73%) had pN0 disease. The probability of missing lymph node metastasis decreased as the number of nodes examined increased. If only a single node was examined, 44% of patients would have been misclassified as having pN0 disease while harboring lymph node metastasis. Even when 5 nodes were examined, 12% of patients would have been misclassified. The proportion of those with a positive node increased with advancing pathological T stage and lymphovascular invasion. Patients with pT0-Ta-Tis-T1/lymphovascular invasion had more than a 95% chance of correct pathological nodal staging with 2 examined nodes. However, if a patient had pT3-T4 and positive lymphovascular invasion, even 20 examined lymph nodes did not attain 95% accuracy., Conclusions: Lymph node dissection provides more accurate staging and prediction of survival. The number of examined nodes needed for adequate staging depends on pT stage and lymphovascular invasion. We developed a tool to estimate the likelihood of false-negative lymph node metastasis, which could help refine clinical decision making regarding the administration of adjuvant chemotherapy., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate temporal trends in clinicopathological features and oncological outcomes after radical nephroureterectomy for upper tract urothelial carcinoma., Methods: Utilizing a multi-institutional database of patients treated with radical nephroureterectomy between 1983 and 2007, we compared clinicopathological features and survival outcomes over the past three decades using the following cohorts: group 1 comprised of patients treated before the 1990s (n = 106), group 2 from 1990 to1999 (n = 655), and group 3 from 2000 to 2007 (n = 701). Survival rates were compared using Kaplan-Meier survival analysis., Results: The study included 1462 patients, 992 men and 470 women, with 36 months median follow up (range 1-250 months) after radical nephroureterectomy. Tumors were organ confined (≤T2/N0) in 88% and high-grade in 64%. Neoadjuvant and adjuvant systemic chemotherapy was administered in 47 (3.2%) and 171 (11.7%) patients, respectively. There was a significant increase in the use of laparoscopic radical nephroureterectomy, endoscopic management of urothelial carcinoma and utilization of perioperative chemotherapy between decades 1 to 3. There were no significant differences in pathological stage distribution. The overall 5-year disease-free survival rates were 66 ± 5%, 68.5 ± 2% and 71 ± 2%, and the 5-year cancer-specific survival rates were 75 ± 5%, 72 ± 2%, and 75 ± 2% for groups 1, 2 and 3, respectively, with no significant statistical differences between the three decades (P > 0.05)., Conclusion: Outcomes after radical nephroureterectomy have not changed significantly over the past three decades, despite staging and surgical refinements. Utilization of perioperative systemic chemotherapy in urothelial carcinoma management remains low. Further improvements in outcomes of urothelial carcinoma patients necessitate rigorous investigation of multimodal treatment approaches., (© 2012 The Japanese Urological Association.)

Purpose: To describe the natural history and identify predictors of cancer-specific survival in patients who experience disease recurrence after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC)., Methods: Of 2,494 UTUC patients treated with RNU without neoadjuvant chemotherapy, 597 patients experienced disease recurrence. A total of 148 patients (25 %) received adjuvant chemotherapy before disease recurrence. Multivariable Cox regression model addressed time to cancer-specific mortality after disease recurrence., Results: The median time from RNU to disease recurrence was 12 months (interquartile range 5-22). A total of 491 (82 %) of 597 patients died from UTUC, and 8 patients (1.3 %) died from other causes. The median time from disease recurrence to death of UTUC was 10 months. Actuarial cancer-specific survival estimate at 12 months after disease recurrence was 35 %. On multivariable analysis that adjusted for the effects of standard clinicopathologic characteristics, higher tumor stages [hazard ratio (HR) pT3 vs. pT0-T1: 1.66, p = 0.001; HR pT4 vs. pT0-T1: 1.90, p = 0.002], absence of lymph node dissection (HR 1.28, p = 0.041), ureteral tumor location (HR 1.44, p < 0.0005) and a shorter interval from surgery to disease recurrence (p < 0.0005) were significantly associated with cancer-specific mortality. The adjusted 6-, 12- and 24-month postrecurrence cancer-specific mortality was 73, 60 and 57 %, respectively., Conclusions: Approximately 80 % of patients who experience disease recurrence after RNU die within 2 years after recurrence. Patients with non-organ-confined stage, absence of lymph node dissection, ureteral tumor location and/or shorter time to disease recurrence died of their tumor more quickly than their counterparts. These factors should be considered in patient counseling and risk stratification for salvage treatment decision making.

Background: Novel prognostic factors for patients after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) have recently been described., Objective: We tested the prognostic value of pathologic characteristics and developed models to predict the individual probabilities of recurrence-free survival (RFS) and cancer-specific survival (CSS) after RNU., Design, Setting, and Participants: Our study included 2244 patients treated with RNU without neoadjuvant or adjuvant therapy at 23 international institutions. Tumor characteristics included T classification, grade, lymph node status, lymphovascular invasion, tumor architecture, location, and concomitant carcinoma in situ (CIS). The cohort was randomly split for development (12 centers, n=1273) and external validation (11 centers, n=971)., Interventions: All patients underwent RNU., Measurements: Univariable and multivariable models addressed RFS, CSS, and comparison of discrimination and calibration with American Joint Committee on Cancer (AJCC) stage grouping., Results and Limitations: At a median follow-up of 45 mo, 501 patients (22.3%) experienced disease recurrence and 418 patients (18.6%) died of UTUC. On multivariable analysis, T classification (p for trend <0.001), lymph node metastasis (hazard ratio [HR]: 1.98; p=0.002), lymphovascular invasion (HR: 1.66; p<0.001), sessile tumor architecture (HR: 1.76; p<0.001), and concomitant CIS (HR: 1.33; p=0.035) were associated with disease recurrence. Similarly, T classification (p for trend<0.001), lymph node metastasis (HR: 2.23; p=0.001), lymphovascular invasion (HR: 1.81; p<0.001), and sessile tumor architecture (HR: 1.72; p=0.001) were independently associated with cancer-specific mortality. Our models achieved 76.8% and 81.5% accuracy for predicting RFS and CSS, respectively. In contrast to these well-calibrated models, stratification based upon AJCC stage grouping resulted in a large degree of heterogeneity and did not improve discrimination., Conclusions: Using standard pathologic features, we developed highly accurate prognostic models for the prediction of RFS and CSS after RNU for UTUC. These models offer improvements in calibration over AJCC stage grouping and can be used for individualized patient counseling, follow-up scheduling, risk stratification for adjuvant therapies, and inclusion criteria for clinical trials., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: The prognostic impact of multifocal upper-tract urothelial carcinoma (UTUC) is poorly understood., Objective: To investigate the association between tumor multifocality and clinicopathologic features and outcomes of UTUC in patients managed by radical nephroureterectomy (RNU)., Design, Setting, and Participants: The study included 2492 patients treated with either open or laparoscopic RNU. Tumor and patient characteristics included tumor stage, tumor grade, lymph node status, lymphovascular invasion (LVI), tumor architecture, tumor location, unifocal or multifocal disease, gender, age, history of bladder cancer (BCa), Eastern Cooperative Oncology Group (ECOG) performance status (PS), and adjuvant chemotherapy. tumor multifocality of UTUC was defined as the synchronous presence of multiple tumors in the renal pelvis or ureter., Intervention: All patients were treated with either open or laparoscopic RNU., Measurements: Univariable and multivariable models tested the effect of tumor multifocality on disease progression and cancer-specific mortality., Results and Limitations: Five hundred ninety patients (23.7%) had tumor multifocality at the time of RNU. The median follow-up was 45 mo (interquartile range [IQR]: 0-101). Tumor multifocality was significantly associated with a history of previous BCa (p=0.032), lymph node involvement (p=0.036), tumor location in the ureter (p=0.003), higher tumor stage (p<0.001), higher tumor grade (p<0.001), sessile tumor architecture (p=0.003), and LVI (p=0.001). In organ-confined patients, tumor multifocality was an independent predictor of both disease progression (hazard ratio [HR]: 1.43; p=0.019) and cancer-specific mortality (HR: 1.46; p=0.027). When assessed in all patients, tumor multifocality was associated with both disease progression and cancer-specific mortality in univariable (p=0.005 and p=0.006, respectively) but not in multivariable analyses (p=0.468 and p=0.798, respectively). The main limitation is the retrospective design of the study., Conclusions: Tumor multifocality is an independent prognosticator of disease progression and cancer-specific mortality in patients with organ-confined UTUC treated with RNU. Multifocal organ-confined patients with UTUC may need closer follow-up. Integration of tumor multifocality with other factors may help identify those patients who would benefit from multimodal therapy., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: • To describe a multicentre experience with preoperative platinum-based chemotherapy before radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC) with loco-regional nodal metastases., Patients and Methods: • We identified 313 patients from the UTUC Collaboration (over 1200 patients), who underwent RNU with concomitant retroperitoneal lymph node dissection between 1990 and 2007 and met the inclusion criteria for one of three groups. • Group 1 comprised patients who received chemotherapy before RNU because of biopsy-proven loco-regional nodal metastases. • Group 2 consisted of patients who underwent primary RNU and were found to have metastatic nodal disease on final pathological review (node-positive). • Group 3 comprised a comparative cohort of patients treated with primary RNU for invasive or locally advanced (pT2/pT4) node-negative (N0) UTUC., Results: • Groups 1, 2 and 3 included 18, 120 and 175 patients, respectively. The 5-year disease-free survival rates were 49%, 30% and 64%, whereas the 5-year cancer-specific survival rates were 44%, 36% and 69% in groups 1, 2 and 3, respectively. • In group 1, on final pathological evaluation, nine patients were pN0, six patients were pT0 and five patients had pT0N0 disease. Kaplan-Meier survival analyses showed similar recurrence and survival rates in group 1 compared with group 3 (P= 0.14 and P= 0.06, respectively). • Meanwhile, group 2 had significantly lower disease-free and cancer-specific survival rates compared with group 3 (P < 0.001 and P < 0.001, respectively) and compared with group 1 (P= 0.04 and P= 0.06, respectively)., Conclusions: • Preoperative chemotherapy followed by aggressive surgical consolidation may yield favourable oncological outcomes in patients with UTUC with loco-regional nodal metastases. • These data support further evaluation of neoadjuvant systemic therapy in patients at risk for locally advanced UTUC., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Context: The role of lymph node dissection (LND) in patients treated with radical nephroureterectomy (RNU) for upper tract urothelial cancer (UTUC) is still controversial., Objective: To analyze the impact of lymph node invasion on the outcome of patients, the staging, and the possible therapeutic role of LND in UTUC., Evidence Acquisition: A Medline search was conducted to identify original articles, review articles, and editorials addressing the role of LND in UTUC. Keywords included upper tract urothelial neoplasms, lymphadenectomy, lymph node excision, lymphatic metastases, nephroureterectomy, imaging, and survival., Evidence Synthesis: Regional nodes are frequently involved in UTUC and represent the most common metastatic site. Regional nodal status is a significant predictor of patient outcomes, especially in invasive disease. Therefore, select patients treated with RNU at high risk for regional nodal metastases should undergo LND to improve disease staging, which would identify those who could benefit from adjuvant systemic therapy. Several retrospective studies suggested the potential therapeutic role of LND in UTUC. An accurate LND could remove some nodal micrometastases not identified on routine pathologic examination, thus improving local control and cancer-specific survival. Radical surgery and LND might be curative in a subpopulation with limited nodal disease, as described in bladder cancer. A clear knowledge of the limits of LND and a template of LND for UTUC are still needed., Conclusions: An extended LND can provide better disease staging and may be curative in patients with limited nodal disease. However, current evidence is based on retrospective studies, which limits the ability to standardize either the indication or the extent of LND. Prospective trials are required to determine the impact of LND on survival in patients with UTUC and identify patients for a risk-adapted approach such as close follow-up or adjuvant chemotherapy., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Abstract We investigated whether a history of endoscopic tumor ablation impacts oncologic outcomes after radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC). Using a multi-institutional database that contained patients who were treated with RNU, oncologic outcomes were assessed according to history of ureteroscopic tumor ablation. Disease-free survival (DFS) and cancer-specific survival (CSS) were estimated using the Kaplan-Meier survival analysis. Multivariate Cox regression analyses were performed to determine independent predictors of disease recurrence and cancer-specific mortality after RNU. The study included 1268 patients, 853 men and 415 women, with a mean age of 67.5 years (range 32-94 y) and 52.8 months median follow-up after RNU. A total of 175 (13%) patients underwent RNU after endoscopic tumor ablation and 1093 (87%) patients underwent RNU without a history of endoscopic ablation. The 5-year DFS and CSS rates were 72% and 77% in those with a history of tumor ablation vs 69% and 73% in those without a history of ablation (P = 0.171 and P = 0.365, respectively). In multivariate Cox regression analysis, history of ablation therapy was not associated with disease recurrence or cancer-specific mortality (hazard ratio [HR]: 0.79, P = 0.185 and HR: 0.7, P = 0.078, respectively). Our collaborative international efforts suggest that in selected patients, endoscopic tumor ablation does not adversely affect the recurrence and survival after subsequent RNU for UTUC. Our data support the continued role of ureteroscopic ablation of UTUC in appropriately selected patients.

Purpose: To compare direct costs associated with open partial nephrectomy (OPN), laparoscopic partial nephrectomy (LPN), and robot-assisted LPN (RALPN)., Methods: A meta-analysis of nonoverlapping studies was performed to determine operating room (OR) time, equipment use, and length of stay (LOS) for OPN, LPN, and RALPN. Cost models using cost data obtained from our institution were created, and robotic cost and maintenance were amortized over 7 years. One- and two-way sensitivity analyses were performed to evaluate the effect of changing variables on the cost effectiveness of each approach., Results: Seven RALPN, 18 LPN, and 8 OPN data series were identified, comprising a total of 477, 2220, and 2745 procedures, respectively. Weighted mean OR time was 188, 200, 193 minutes; weighted mean LOS was 2.6, 3.2, and 5.9 days for RALPN, LPN, and OPN, respectively. LPN was the most cost-effective approach at a mean direct cost of $10,311, with a cost advantage of $1116 and $1652 over OPN ($11,427) and RALPN ($11,962), respectively. Sensitivity analyses demonstrate that significant decreases in robotic costs are required for RALPN to be cost effective., Conclusion: Despite similar OR times, LPN is more cost effective than OPN because of shorter LOS. Because of lower instrumentation costs, LPN is the most cost effective despite a longer LOS than RALPN. RALPN has high cost of maintenance and instrumentation, which is partially compensated by the shorter LOS. Evidence of oncological and functional equivalence to OPN is warranted to determine the future role of RALPN.

Objectives: Hydronephrosis at the time of diagnosis of bladder cancer is associated with advanced disease and is a predictor of poorer outcomes. There is, however, limited information addressing whether a similar relationship exists for upper-tract urothelial carcinoma (UTUC). We investigate the prognostic impact of hydronephrosis on preoperative axial imaging on clinical outcomes after radical nephroureterectomy., Materials and Methods: The records for 106 patients with UTUC who underwent radical nephroureterectomy at 2 medical centers were reviewed. Preoperative computed tomography (CT) images were evaluated for ipsilateral hydronephrosis by radiologists blinded to clinical outcomes. Association of hydronephrosis with pathologic features and oncologic outcomes after surgery was assessed., Results: Sixty-seven men and 39 women with a median age of 69 years (range, 36 to 90) were evaluated. One-third of these patients had muscle invasive disease or greater (≥T2), 44% had high grade tumors, and 3% had lymph node (LN) metastases. At a median follow-up of 47 months (range, 1 to 164), 43% of patients experienced disease recurrence, 18% developed metastasis, and 12% died of their cancer. Thirty-nine patients (37%) had hydronephrosis on preoperative axial imaging; 35% of these patients had ureteral tumors, and 27% had multifocal disease. The presence of hydronephrosis was associated with advanced pathologic stage (P = 0.03) and disease in the ureter (vs. renal pelvis) (P = 0.007). Hydronephrosis was a predictor of non-organ confined disease on final pathology (hazard ratio [HR] 3.7, P = 0.01). On preoperative multivariable analysis controlling for age, gender, tumor location, ureteroscopic biopsy grade, and urinary cytology, hydronephrosis was independently associated with cancer metastasis (HR 8.2, P = 0.02) and cancer-specific death (HR 12.1, P = 0.03)., Conclusions: Preoperative hydronephrosis on axial imaging is associated with features of aggressive disease and predicts advanced pathologic stage for UTUC. Hydronephrosis can be a valuable prognostic tool for preoperative planning and counseling regarding disease outcomes., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To assess the impact of patient age on outcomes after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC)., Patients and Methods: Data were collected on 1453 patients treated with RNU at 13 centres. Pathological slides were reviewed by dedicated genitourinary pathologists according to standardized criteria. Age at RNU was analysed both as a continuous and categorical variable (<50, n = 85; 50-59.9, n = 229; 60-69.9, n = 416; 70-79.9, n = 523; > or =80 years, n = 200). RESULTS Patients aged <50 years were less likely to have undergone previous ureteroscopy and to have a history of bladder cancer (P < or = 0.026). Advanced age was associated with infiltrative architecture and female gender (P < or = 0.003). Patients aged >70 years were less likely to undergo lymphadenectomy and to receive adjuvant chemotherapy (P < or = 0.026). In multivariable analyses, being older was associated with decreased all-cause (AC) survival (>60 years) and cancer-specific survival (CSS; >80 years) after controlling for the effects of standard pathological features (P < or = 0.006). However, addition of age did not improve the predictive accuracy of a base model that included standard pathological features for prediction of either disease recurrence, AC survival or CSS., Conclusions: Being older at the time of RNU was associated with decreased survival. This finding could be due to a change in the biological potential of the tumour cell, a decrease in the host's defence mechanisms, or differences in care patterns. Further work is needed to improve our understanding of UTUC outcomes in this growing segment of the population and to develop strategies to improve cancer control in the elderly.

Study Type: Prognosis (case series)., Level of Evidence: 4., Objective: To examine the association between the delay from diagnosis of upper-tract urothelial carcinoma (UTUC) to radical nephroureterectomy (RNU), and the pathological features and outcomes, as the decision to proceed to RNU for an individual patient is complex., Patients and Methods: The records of 187 patients who had RNU were reviewed; the interval from diagnosis to RNU was analysed as both a continuous (months) and categorical variable (<3 vs > or =3 months). Logistic regression and survival analyses were used to evaluate the association between time from diagnosis to RNU with pathological characteristics and clinical outcomes., Results: The median time from diagnosis to RNU was 45 days (interquartile range 68). A delay from diagnosis to RNU analysed as a continuous variable was associated with advanced stage, higher grade, previous endoscopic procedure, tumour necrosis, infiltrative tumour architecture, and lymphovascular invasion (P = 0.034), but not disease recurrence or cancer-specific mortality. In the subgroup of patients (90, 48.1%) who had muscle-invasive disease (> or =pT2) a longer delay from diagnosis to RNU as a continuous variable was associated with advanced stage (P = 0.030), higher grade (P = 0.014), infiltrative tumour architecture (P = 0.044), lymphovascular invasion (P = 0.034), disease recurrence (P = 0.02), and cancer-specific mortality (P = 0.03)., Conclusions: Our data suggest that a delay in the interval from diagnosis to RNU is associated with more advanced disease stage. These findings might have important implications for trial design in the ongoing evaluation of neoadjuvant regimens. Timely consideration of definitive treatment for patients with high-risk UTUC is of high importance. Further studies are necessary to validate these hypothesis-generating findings.

Purpose: We examined the impact of lymphadenectomy on the clinical outcomes of patients with upper tract urothelial cancer treated with radical nephroureterectomy., Materials and Methods: Data were collected on 1,130 consecutive patients with pT1-4 upper tract urothelial cancer treated with radical nephroureterectomy at 13 centers worldwide. Patients were grouped according to nodal status (pN0 vs pNx vs pN+). The choice to perform lymphadenectomy was determined by the treating surgeon. All pathology slides were reevaluated by dedicated genitourinary pathologists. Univariable and multivariable Cox regression models measured the association of nodal status (pN0 vs pNx vs pN+) with cancer specific survival., Results: Overall 412 patients (36.5%) had pN0 disease, 578 had pNx disease (51.1%) and 140 had pN+ disease (12.4%). The 5-year cancer specific survival estimate was lower in patients with pN+ compared to those with pNx disease (35% vs 69%, p <0.001), which in turn was lower than that in those with pN0 disease (69% vs 77%, p = 0.024). In the subgroup of patients with pT1 disease (345) cancer specific survival rates were not different in those with pN0 and pNx. In pT2-4 cases (813) cancer specific survival estimates were lowest in pN+, intermediate in pNx and highest in pN0 (33% vs 58% vs 70%, p = 0.017). When adjusted for the effects of standard clinicopathological features pN+ was an independent predictor of cancer specific survival (p <0.001). pNx was significantly associated with worse prognosis than pN0 in pT2-4 upper tract urothelial cancer only., Conclusions: Nodal status is a significant predictor of cancer specific survival in upper tract urothelial cancer. pNx is significantly associated with a worse prognosis than pN0 in pT2-4 tumors. Patients expected to have pT2-4 disease should undergo lymphadenectomy to improve staging and thereby help guide decision making regarding adjuvant chemotherapy.

Background: The literature on upper tract urothelial carcinoma (UTUC) has been limited to small, single center studies. A large series of patients treated with radical nephroureterectomy for UTUC were studied, and variables associated with poor prognosis were identified., Methods: Data on 1363 patients treated with radical nephroureterectomy at 12 academic centers were collected. All pathologic slides were re-reviewed by genitourinary pathologists according to strict criteria., Results: Pathologic review revealed renal pelvis location (64%), necrosis (21.6%), lymphovascular invasion (LVI) (24.8%), concomitant carcinoma in situ (28.7%), and high-grade disease (63.7%). A total of 590 patients (43.3%) underwent concurrent, lymphadenectomy and 135 (9.9%) were lymph node (LN) -positive. Over a mean follow-up of 51 months, 379 (28%) patients experienced disease recurrence outside of the bladder and 313 (23%) died of UTUC. The 5-year recurrence-free and cancer-specific survival probabilities (+/-SD) were 69%+/-1% and 73%+/-1%, respectively. On multivariate analysis, high tumor grade (hazards ratio [HR]: 2.0, P<.001), advancing pathologic T stage (P-for-trend<.001), LN metastases (HR: 1.8, P<.001), infiltrative growth pattern (HR: 1.5, P<.001), and LVI (HR: 1.2, P=.041) were associated with disease recurrence. Similarly, patient age (HR: 1.1, P=.001), high tumor grade (HR: 1.7, P=.001), increasing pathologic T stage (P-for-trend<.001), LN metastases (HR: 1.7, P<.001), sessile architecture (HR: 1.5, P=.002), and LVI (HR: 1.4, P=.02) were independently associated with cancer-specific survival., Conclusions: Radical nephroureterectomy provided durable local control and cancer-specific survival in patients with localized UTUC. Pathologic tumor grade, T stage, LN status, tumor architecture, and LVI were important prognostic variables associated with oncologic outcomes, which could potentially be used to select patients for adjuvant systemic therapy., (Copyright (c) 2009 American Cancer Society.)

Objective: To assess whether tumour architecture can help to refine the prognosis of patients treated with nephroureterectomy (NU) for urothelial carcinoma (UC) of the upper urinary tract (UT), as the prognostic value of tumour architecture (papillary vs sessile) in UTUC remains elusive., Patients and Methods: The study included 1363 patients with UTUC and treated with radical NU at 12 centres worldwide. All slides were re-reviewed according to strict criteria by genitourinary pathologists who were unaware of the findings of the original pathology slides and clinical outcomes. Gross tumour architecture was categorized as sessile vs papillary., Results: Papillary growth was identified in 983 patients (72.2%) and sessile growth in 380 (27.8%). The sessile growth pattern was associated with higher tumour grade, more advanced stage, lymphovascular invasion, and metastasis to lymph nodes (all P < 0.001). In multivariable Cox regression analyses that adjusted for the effects of pathological stage, grade and lymph node status, tumour architecture (sessile or papillary) was an independent predictor of cancer recurrence (hazard ratio 1.5, P = 0.002) and cancer-specific mortality (1.6, P = 0.001). Adding tumour architecture increased the predictive accuracy of a model that comprised pathological stage, grade and lymph node status for predicting cancer recurrence and cancer-specific death by a minimal but statistically significant margin (gain in predictive accuracy 1% and 0.5%, both P < 0.001)., Conclusion: The tumour architecture of UTUC is associated with established features of biologically aggressive disease, and more importantly, with prognosis after radical NU. Including tumour architecture in predictive models for disease progression should be considered, aiming to identify patients who might benefit from early systemic therapeutic intervention.

Objective: To determine the risk factors associated with clinical outcome in patients with lymph node (LN)-positive urothelial carcinoma of the upper urinary tract (UTUC) treated with radical nephroureterectomy (RNU) and lymphadenectomy, focusing on the concept of LN density (LND)., Patients and Methods: Patients undergoing RNU with regional lymphadenectomy were identified through multi-institutional databases. All pathology slides were re-evaluated by genitourinary pathologists unaware of the clinical data. The exposure variable used was LND (continuously coded and that of all possible thresholds) with recurrence-free and disease-specific survival (DSS) serving as the outcome measures., Results: Of 432 patients undergoing RNU with lymphadenectomy, 135 (31%) had LN metastases. Within a median follow-up of 4.1 years, 90 of the 135 patients with LN metastases (68%) had disease recurrence and 76 (58%) died from UTUC. The mean (sem) 5-year recurrence-free and DSS probabilities were 27 (4)% and 33 (5)%, respectively. The median (range) LND was 50 (3-100)%. The most informative threshold for LND in relation to outcome was 30%. In multivariable analyses that adjusted for the effects of tumour stage and grade, patients with a LND of > or =30% were at greater risk of both cancer recurrence, with 5-year rates of 25 (5)% vs 38 (8)% (hazard ratio 1.8, P = 0.021) and mortality, with 5-year rates of 30 (6)% vs 48 (9)% (1.7, P = 0.032) compared to those with a LND of <30%. Our results are primarily limited by a lack of standardization in the lymphadenectomy template., Conclusion: We evaluated the concept of LND for the first time in UTUC. LND provides additional prognostic information in patients with node-positive disease after RNU. The use of LND in clinical trials might provide an additional insight into the value of LN dissection in patients undergoing RNU.

Objectives: To assess the sex differences in the clinical and pathologic characteristics of upper tract urothelial carcinoma (UTUC) and to determine the effect on prognosis after radical nephroureterectomy (RNU) in a large multicenter series., Methods: The records of 1363 patients who had undergone RNU were reviewed from the UTUC Collaboration database. The median follow-up was 47 months (range 0-250). The pathologic slides were re-evaluated by genitourinary pathologists unaware of the original findings from the slides and the clinical outcomes. The endpoints were freedom from tumor recurrence and disease-specific survival., Results: The male-to-female ratio was 2.1:1. The women were older than the men at diagnosis (70 +/- 11 vs 68 +/- 11 years; P < .001). No significant sex-related differences were found in the presence of symptoms at presentation (P = .70), pathologic stage (P = .98), tumor grade (P = .28), tumor architecture (P = .27), presence of lymphovascular invasion (P = .42), presence of concomitant carcinoma in situ (P = .08), or the presence of lymph node metastases (P = .24). Recurrence developed in 379 patients (28%), and 313 patients (23%) died of their disease. Sex was not associated with disease recurrence (P = .07) or disease-specific survival (P = .13). An adjustment for the effects of the pathologic features did not change the lack of association of sex with the clinical outcomes., Conclusions: To our knowledge, this is the largest series analyzing the effect of sex on the outcomes after RNU. No difference was found in the clinicopathologic features or prognosis between women and men treated with RNU for UTUC. The results of this large, international series show that RNU provides durable local control and disease-specific survival for both men and women with UTUC.

Objective: To compare the outcomes of patients treated for upper tract urothelial carcinoma with either immediate nephroureterectomy (NU) or initial endoscopic management., Patients and Methods: The treatments of 108 patients (120 renal units) at the authors' institution were retrospectively reviewed and divided into two groups, i.e. those who received immediate NU and those who had conservative initial therapy, which included renal units solely treated with endoscopy with or without delayed NU. Overall and disease-specific survival (DSS) were compared between the treatment groups., Results: There were 48 low-grade tumours, of which 27 (56%) were managed conservatively and 21 (44%) by immediate NU. Seven patients treated conservatively had stage or grade progression and had delayed NU. The mean (sd) DSS at 5 years in patients with low-grade disease was equally good for conservative treatment and immediate NU, at 86.2 (9.1)% vs 87.4 (8.4)% (P = 0.909). There were 68 high-grade tumours, of which 12 (18%) patients had conservative management and 56 (82%) had immediate NU. Among the former, seven of 12 had a solitary kidney and three had bilateral disease. In patients managed endoscopically, four of 30 (13%) required delayed NU. The DSS for the conservative and immediate NU groups were 68.6 (18.6)% vs 75.0 (8.1)% (P = 0.528)., Conclusion: Management with a conservative approach in selected patients provides comparable outcomes to immediate NU in patients with low-grade disease.

Purpose: We analyzed the impact of obesity on the costs of partial and radical nephrectomy., Materials and Methods: The charts of 237 patients who underwent open radical nephrectomy (48), laparoscopic radical nephrectomy (67), open partial nephrectomy (61) or laparoscopic partial nephrectomy (61) were retrospectively reviewed. Clinical data were collected, including age, American Society of Anesthesiologists score, body mass index, tumor size, complications and length of stay. Cost data comprised total direct costs and subcosts, including anesthesia, laboratory, operating room service, radiology, room and board, pharmacy and surgical supplies. Obese and nonobese patients were compared in each group using the Mann-Whitney U and chi-square tests for continuous and categorical variables, respectively. Univariate analysis was used to assess predictors of direct costs., Results: Length of stay was longer in obese patients in the open partial nephrectomy group (p = 0.04). There were no differences between obese and nonobese patients in terms of complications and comorbidities. Costs were higher in obese patients in the open partial nephrectomy group ($10,187 vs $6,538, p = 0.02). There were no other differences in cost between obese and nonobese patients in the 3 other surgical groups. On univariate analysis length of stay robustly predicted the cost of each kind of operation (p <0.0001). Obesity status was almost a significant predictor of direct cost in the open partial nephrectomy group (p = 0.056)., Conclusions: Body mass index had an impact on costs only in the subset of patients who underwent open partial nephrectomy. Length of stay seems to be the main determinant of costs in renal surgery. Further studies are warranted.

Objective: To compare the costs and morbidity of laparoscopic radiofrequency ablation (LRFA) and laparoscopic partial nephrectomy (LPN) for treating small localized renal tumours., Patients and Methods: We retrospectively analysed the outcomes of 88 patients treated at our institution for a renal tumour either by LPN (50) or LRFA (38) between March 2000 and May 2006. Patients with multiple tumours, combined LRFA and LPN, and those who had other simultaneous surgical procedures were excluded. Clinical variables and outcomes were analysed for each patient. Direct cost data were available for 40 patients treated with LPN and 14 with LRFA. Continuous and categorical variables were compared using an independent t-test and chi-square test, respectively., Results: The tumour size was comparable in each group; patients in the LRFA group had more comorbidities (P = 0.01) and a higher overall mortality rate (P = 0.01) but no patient died from cancer. Operative duration, estimated blood loss and length of stay were significantly shorter in the LRFA group but there was no difference in complication rate. LRFA was less costly than LPN ($6103 vs $6808, P = 0.3) but not statistically significantly. The cost savings from the shorter operative duration and length of stay were reduced by the cost of probe. With a median follow-up of 20 months there was no difference in oncological outcome., Conclusion: Patients undergoing LRFA tend to be older and have more comorbidities than those treated with LPN. The cost is minimally lower for LRFA, secondary to the added cost of the probe. LRFA might be a good alternative treatment in patients at higher risk of surgical complications, but LPN provides good results when done by an experienced surgeon.

Introduction: Laparoscopic partial nephrectomy (LPN) is less morbid than open partial nephrectomy (OPN), but the high cost of new technologies used in LPN may make this a significantly more expensive procedure. In this study, the overall costs of OPN and LPN were compared using data extracted from the literature, and a series of sensitivity analyses were performed to determine the impact of individual cost components on overall cost., Materials and Methods: Data on operating room (OR) time, equipment use, and length of stay (LOS) were abstracted after a comprehensive literature review of LPN and OPN. Decision tree models were devised to estimate the cost of each treatment using the DATA program (TreeAge software 3.5). LPN model assumptions included one that used all reusable equipment, all disposable equipment, and a hand-assist model. One and two-way sensitivity analyses were performed to evaluate the effect of individual treatment variables on overall cost., Results: The literature yielded 12 OPN and 13 LPN articles, comprising a total of 574 and 949 patients, respectively. The weighted mean LOS were 5.7 and 2.9 days (<0.001); average tumor sizes were 3.2 cm and 2.5 cm (P = 0.016); and the weighted mean OR times were 184 and 187 minutes for OPN and LPN (P = 0.7), respectively. The LPN model using all disposable equipment is less costly than OPN by $431 ($8450 v $8019). The slight cost superiority of the laparoscopic approach was driven by shorter LOS. One-way sensitivity analyses showed that LPN is less costly if the OR time of LPN is less than 146 minutes; LOS after LPN is less than 4.6 days; or LPN OR supply costs are less than $1670. Two-way sensitivity analyses demonstrated the effects of modifying OR time, LOS, and surgical equipment on the cost-equivalence of LPN and OPN., Conclusions: Laparoscopic partial nephrectomy can be cost equivalent to the open approach in managing small renal masses if the OR time, LOS, and equipment costs are closely monitored. The high cost of new technologies can be offset by shorter LOS and decrease in OR time.

Objective: To compare the intermediate-term outcomes of patients with clinical T1a renal tumours who were treated with nephron-sparing surgery by partial nephrectomy (PN), the preferred approach for small (cT1a) renal tumours, or radiofrequency ablation (RFA), recently offered to selected patients as an alternative, less morbid technique., Patients and Methods: We identified patients with stage T1a renal masses who had > or = 2 years of follow-up; those with bilateral synchronous or metachronous tumours, metastatic disease at presentation, or a family history of renal cell carcinoma were excluded. From July 1996 to January 2004 110 PNs were identified in our database; 37 patients who fulfilled the inclusion criteria had either open (30) or laparoscopic PN (seven) and 40 had either percutaneous (26) or laparoscopic (14) RFA., Results: The mean (range) follow-up for the RFA and PN groups was 30 (18-42) and 47 (24-93) months, respectively; the respective mean tumour size was 2.41 and 2.43 cm. There was one incomplete ablation and two local recurrences in the RFA group, and two recurrences in the PN group (one local and one in the contralateral kidney). There were no disease-specific deaths. The overall actuarial disease-free probability for the PN and RFA groups, respectively, was 95.8% and 93.4% (P = 0.67)., Conclusions: This initial 3-year actuarial analysis showed that RFA for cT1a renal tumours has comparable oncological outcomes to PN; however, longer term data are still needed.

Purpose: We compared clinical and pathological staging in a contemporary, consecutive series of patients treated with partial or radical nephrectomy for renal cell carcinoma and we determined the effect of clinical and pathological stage discrepancy on outcomes., Materials and Methods: We collected retrospective clinical, pathological and survival data on 264 consecutive patients with clinical T1-3 renal cell carcinoma who were treated with laparoscopic or open partial or radical nephrectomy at a single institution from 1994 to 2003., Results: Pathological up staging occurred in 44 of 264 patients (17%) patients. Of 135 clinical T1 tumors 25 (18.5%) and 18 of 85 (21.2%) clinical T2 tumors were pathologically up staged. Patients with clinical T1 and T2 tumors were stratified into 2 groups, including those with the same clinical and pathological stage, and those with pathological up staging. Mean 5-year recurrence-free survival +/- SD for same stage vs pathologically up staged clinical T1 (84.3% +/- 4.4% vs 47.4% +/- 11.5%) and clinical T2 (80.0% +/- 6.8% vs 40.7% +/- 13.4%) tumors was significantly different (p < 0.0002). Five-year cancer specific survival for same stage vs pathologically up staged clinical T1 tumors was significantly different (98.5% +/- 1.5% vs 69.7% +/- 11.3%, p = 0.0005), while that for clinical T2 tumors approached clinical significance (90.9% +/- 5.0% vs 72.7% +/- 13.4%, p = 0.0501)., Conclusions: Stage discrepancy is common in surgically treated patients diagnosed with renal masses and it has a significant impact on clinical outcome. Implications of such clinical and pathological stage discrepancy should be considered when counseling patients and determining therapeutic approaches.