Sarcopenia assessments as predictors of overall survival in patients with metastatic renal cell carcinoma.

BACKGROUND: Sarcopenia represents an important prognostic marker in tumor patients. However, measurement methods and threshold values are not uniformly defined. The aim of this study is therefore to determine the prognostic value of current definitions of sarcopenia in patients with metastatic renal cell carcinoma treated with tyrosine-kinase-inhibitors (TKIs). METHODS: In 93 patients with metastatic renal cell carcinoma, sarcopenia was assessed based on manually assisted software measurements of sarcopenia indices based on different muscle areas. Whole muscle area and psoas muscle area at L3 were estimated and adjusted to patient's height in routine CT imaging before the start of first-line TKI therapy. The correlation of different sarcopenia definitions to overall survival was investigated in a univariate analysis as well as in a multivariate analysis. RESULTS: The mean patients' age at inclusion was 65.8 years (21-86 years). Median survival was 12.3 months (IQR: 5.7-29.8 months), and mean survival was 18.8 months (SD: 17.2 months). As the definitions of sarcopenia differ considerably, 7.6% to 96.7% of the patients were classified as sarcopenic. In univariate analysis, sarcopenia was significantly associated with overall survival. Multivariate analysis, taking into account the Memorial Sloan Kettering Cancer Center risk score, revealed that some sarcopenia-indices are additional and independent prognostic markers. The risk of death was approximately doubled in sarcopenic patients. CONCLUSIONS: Sarcopenia is an important prognostic factor in patients with metastatic renal cell carcinoma treated with TKIs. Multivariate analysis demonstrates a doubling of the risk of death in sarcopenic patients. The assessment of sarcopenia can be performed by the analysis of routine staging imaging using indices of the total muscle area or the psoas muscle area.

Geriatric Assessments Can Predict Functional Outcome and Mortality after Urological Tumor Surgery.

INTRODUCTION: Older patients undergoing major urological tumor surgery are at severe risk of functional deterioration, complications, and mortality. We prospectively evaluated geriatric assessment tools and developed a novel easy-to-use assessment tool for clinical use. METHODS: In 159 patients, geriatric assessment tools were used prior to cystectomy, prostatectomy, and renal tumor surgery, and their peri- and postoperative courses were recorded. Using all the tests, a short and easy-to-use assessment tool was developed, and nomograms were generated to predict functional outcomes and mortality. RESULTS: Of all the patients, 13.8% underwent radical cystectomy, 37.7% underwent radical prostatectomy, and 48.4% underwent tumor surgery of the kidney at the age of 70 years or older. The average age was 75.6 years. Incomplete functional recovery at day 30 and day 180 was observed in 37.7% and 36.1% of the patients, respectively, and incomplete functional recovery was associated with impaired mobility, previous care dependency, frailty, comorbidities, and a high ASA score. The only predictor for high-grade complications was comorbidities, whereas mortality was associated with the geriatric screening tool scores, impaired mobility, preoperative care dependency, and comorbidities. The Erlangen Index (EI), a combination of the selected assessment tools, showed a good prediction of early (p = 0.002) and medium-term (p = 0.002) functional outcomes and mortality (p = 0.001). CONCLUSION: Our prospective evaluation confirms the high risk of incomplete functional recovery, high-grade complications, and mortality in older patients undergoing major urological tumor surgery. The EI is an easy-to-use preoperative assessment tool and therefore should be used in preoperative patient counseling.

Serum miRNAs Support the Indication for MRI-Ultrasound Fusion-Guided Biopsy of the Prostate in Patients with Low-PI-RADS Lesions.

Multiparametric MRI (mpMRI) and targeted biopsy of the prostate enhance the tumor detection rate. However, the prediction of clinically significant prostate cancer (PCa) is still limited. Our study tested the additional value of serum levels of selected miRNAs in combination with clinical and mpMRI information for PCa prediction and classification. A total of 289 patients underwent targeted mpMRI-ultrasound fusion-guided prostate biopsy complemented by systematic biopsy. Serum miRNA levels of miRNAs (miR-141, miR-375, miR-21-5p, miR-320b, miR-210-3p, let-7c, and miR-486) were determined by quantitative PCR. Detection of any PCa and of significant PCa were the outcome variables. The patient age, pre-biopsy PSA level, previous biopsy procedure, PI-RADS score, and serum miRNA levels were covariates for regularized binary logistic regression models. The addition of miRNA expression of miR-486 and let-7c to the baseline model, containing only clinical parameters, increased the predictive accuracy. Particularly in patients with PI-RADS ≤3, we determined a sensitivity for detecting significant PCa (Gleason score ≥ 7a corresponding to Grade group ≥2) of 95.2%, and an NPV for absence of significant PCa of 97.1%. This accuracy could be useful to support patient counseling in selected cases.

RNA Sequencing of Collecting Duct Renal Cell Carcinoma Suggests an Interaction between miRNA and Target Genes and a Predominance of Deregulated Solute Carrier Genes.

Collecting duct carcinoma (CDC) is a rare renal cell carcinoma subtype with a very poor prognosis. There have been only a few studies on gene expression analysis in CDCs. We compared the gene expression profiles of two CDC cases with those of eight normal tissues of renal cell carcinoma patients. At a threshold of |log2fold-change| ≥ 1, 3349 genes were upregulated and 1947 genes were downregulated in CDCs compared to the normal samples. Pathway analysis of the deregulated genes revealed that cancer pathways and cell cycle pathways were most prominent in CDCs. The most upregulated gene was keratin 17, and the most downregulated gene was cubilin. Among the most downregulated genes were four solute carrier genes (SLC3A1, SLC9A3, SLC26A7, and SLC47A1). The strongest negative correlations between miRNAs and mRNAs were found between the downregulated miR-374b-5p and its upregulated target genes HIST1H3B, HK2, and SLC7A11 and between upregulated miR-26b-5p and its downregulated target genes PPARGC1A, ALDH6A1, and MARC2. An upregulation of HK2 and a downregulation of PPARGC1A, ALDH6A1, and MARC2 were observed at the protein level. Survival analysis of the cancer genome atlas (TCGA) dataset showed for the first time that low gene expression of MARC2, cubilin, and SLC47A1 and high gene expression of KRT17 are associated with poor overall survival in clear cell renal cell carcinoma patients. Altogether, we identified dysregulated protein-coding genes, potential miRNA-target interactions, and prognostic markers that could be associated with CDC.

Early versus deferred standard androgen suppression therapy for advanced hormone-sensitive prostate cancer.

BACKGROUND: Standard androgen suppression therapy (AST) using surgical or medical castration is considered a mainstay of advanced hormone-sensitive prostate cancer treatment. AST can be initiated early when disease is asymptomatic or deferred when patients suffer symptoms of disseminated prostate cancer. OBJECTIVES: To assess the effects of early versus deferred standard AST for advanced hormone-sensitive prostate cancer. SEARCH METHODS: For this Cochrane Review update, we performed a comprehensive search of multiple databases (CENTRAL, MEDLINE, Embase, Web of Science; last searched November 2018) and two clinical trial registers, with no restrictions on the language of publication or publication status. We also searched bibliographies of included studies and conference proceedings (last searched January 2019). SELECTION CRITERIA: We included all randomised controlled trials (RCTs) with a direct comparison of early versus deferred standard AST. We excluded all other study designs. Participants included had advanced hormone-sensitive prostate cancer receiving surgical or medical castration. DATA COLLECTION AND ANALYSIS: Two review authors independently classified studies and abstracted data. The primary outcomes were time to death of any cause and serious adverse events. Secondary outcomes were time to disease progression, time to death from prostate cancer, adverse events and quality of life. We performed statistical analyses using a random-effects model and assessed the certainty of evidence according to GRADE. We performed subgroup analyses for advanced but non-metastatic disease (T2-4/N+ M0), metastatic disease (M1), and prostate-specific antigen (PSA) relapse. MAIN RESULTS: We identified seven new RCTs since publication of the original review in 2002. In total, we included 10 RCTs.Primary outcomesEarly AST probably reduces the risk of death from any cause over time (hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.75 to 0.90; moderate-certainty evidence; 4767 participants). This corresponds to 57 fewer deaths (95% CI 80 fewer to 31 fewer) per 1000 participants at 5 years for the moderate risk group and 23 fewer deaths (95% CI 32 fewer to 13 fewer) per 1000 participants at 5 years in the low risk group. We downgraded for study limitations. Early versus deferred AST may have little or no effect on serious adverse events (risk ratio (RR) 1.05, 95% CI 0.95 to 1.16; low-certainty evidence; 10,575 participants) which corresponds to 6 more serious adverse events (6 fewer to 18 more) per 1000 participants. We downgraded the certainty of evidence for study limitations and selective reporting.Secondary outcomesEarly AST probably reduces the risk of death from prostate cancer over time (HR 0.69, 95% CI 0.57 to 0.84; moderate-certainty evidence). This corresponds to 62 fewer prostate cancer deaths per 1000 (95% CI 87 fewer to 31 fewer) at 5 years for the moderate risk group and 24 fewer death from prostate cancer (95% CI 34 fewer to 12 fewer) per 1000 men at 5 years in the low risk group. We downgraded the certainty of evidence for study limitations.Early AST may decrease the rate of skeletal events (RR 0.37, 95% CI 0.17 to 0.80; low-certainty evidence) corresponding to 23 fewer skeletal events per 1000 (95% CI 31 fewer to 7 fewer). We downgraded for study limitations and imprecision. It may also increase fatigue (RR 1.41, 95% CI 1.23 to 1.62; low-certainty evidence), corresponding to 31 more men with this complaint per 1000 (95% CI 18 more to 48 more). We downgraded for study limitations and imprecision. It may increase the risk of heart failure (RR 1.90, 95% CI 1.09 to 3.33; low-certainty evidence) corresponding to 27 more events per 1000 (95% CI 3 more to 69 more). We downgraded the certainty of evidence for study limitations and imprecision.Global quality of life is probably similar after two years as assessed with the EORTC QLQ-C30 (version 3.0) questionnaire (mean difference -1.56, 95% CI -4.50 to 1.38; moderate-certainty evidence) with higher scores reflecting better quality of life. We downgraded the certainty of evidence for study limitations. AUTHORS' CONCLUSIONS: Early AST probably extends time to death of any cause and time to death from prostate cancer. It may slightly decrease the rate of skeletal events. Rates of serious adverse events and quality of life may be similar. It may increase fatigue and may increase the risk of heart failure. Better quality trials would be particularly important to better understand the outcomes related to possible treatment-related harm, for which we only found low-certainty evidence.

Expression of PD-1 and CTLA-4 Are Negative Prognostic Markers in Renal Cell Carcinoma.

Immuno-oncological therapy with checkpoint inhibition (CI) has become a new standard treatment in metastatic renal cell carcinoma (RCC), but the prognostic value of the expression of CI therapy target molecules is still controversial. 342 unselected consecutive RCC tumor samples were analyzed regarding their PD-1, PD-L1, and CTLA-4 expression by immunohistochemistry (IHC). The prognostic values for cancer-specific survival (CSS) and overall survival (OS) were analyzed for those not exposed to CI therapy. The expression of PD-1 in tumor-infiltrating mononuclear cells (TIMC) and PD-L1 in tumor cells was detected in 9.4% and 12.3%, respectively (Immune reactive score (IRS) > 0). Furthermore, PD-L1 expression in TIMC (IRS > 0) and CTLA-4 expression in TIMC (>1% positive cells) was detected in 4.8% and 6.3%. PD-1 expression and CTLA-4 expression were significantly associated with a worse OS and CSS in log rank survival analysis and univariate Cox regression analysis. CTLA-4 expression is a prognostic marker that is independently associated with a worse outcome in multivariate Cox regression analysis in the whole cohort (OS: p = 0.013; CSS: p = 0.048) as well as in a non-metastatic subgroup analysis (OS: p = 0.028; CSS: p = 0.022). Patients with combined CTLA-4 expression and PD-1-expression are at highest risk in OS and CSS. In RCC patients, PD-1 expression in TIMC and CTLA-4 expression in TIMC are associated with a worse OS and CSS. The combination of PD-1 expression in TIMC and CTLA-4 expression in TIMC might identify high risk patients. This is, to our knowledge, the first description of CTLA-4 expression to be a prognostic marker in RCC.

Metastatic risk stratification of clear cell renal cell carcinoma patients based on genomic aberrations.

Prognostic markers for the definition of the individual metastatic risk in renal cell carcinoma are still missing. The aim of our study was to establish a total number of specific aberrations (TNSA) genetic score as a new prognostic test for metastatic risk evaluation. Fluorescence in situ hybridization (FISH) was performed on isolated cell nuclei of 100 ccRCCs (50 M1/50 M0) and 100 FFPE sections (second cohort, 32 M1/68 M0). For each chromosomal region (1q21.3, 7q36.3, 9p21.3p24.1, 20q11.21q13.32) cut-off values were determined by receiver-operator curve (ROC)-curve analysis. TNSA was calculated based on the dichotomized specific CNVs. The prognostic significance of CNVs was proven by Cox and logistic regression. TNSA was the best predictor of metastasis and recurrence free survival in both cohorts. We derived an algorithm for risk stratification by combining TNSA and T-category, which increased the prognostic accuracy to 87% (specificity = 86%, sensitivity = 88%). This model divides patients into two risk groups with significantly different RFS, CSS, and OS (P = 3.8×10-5 , P = 5×10-6 and P = 3.57×10-8 respectively). The genetic risk model was superior to Leibovich score and was able to identify patients with metachronous metastatic spread which were incorrectly classified as "low" or "intermediate risk." We present a new tool for individual risk stratification by combining genetic alterations with clinico-pathologic parameters. Interphase FISH proves to be a dependable method for prognostic evaluation in primary tumor tissue on isolated cell nuclei as well as on FFPE sections. Especially in organ-confined tumors the genetic score seems to be an important tool to identify patients at high risk for metastatic disease.

Piwi-like 1 protein expression is a prognostic factor for renal cell carcinoma patients.

The Piwi-like genes belong to the Argonaute gene family and are conserved in plants, animals and humans. In addition to their essential role in the germ line and as stem cell-associated genes, Piwi-like proteins play a role in different cancer types but have yet to be studied in renal cell carcinoma (RCC). We investigated tissue micro arrays (TMAs) with tumor samples of two independent cohorts of RCC patients (N = 265 and N = 345); we used immunohistochemistry to assess the protein expression of Piwi-like 1. Applying an immunoreactive score (IRS), we found Piwi-like 1 positivity (IRS > 0) in 28.3% and 14.8% of the tumors in cohorts 1 and 2, respectively. Piwi-like 1 positivity was correlated with Fuhrman grade, tumor stage and the presence of distant metastasis (P < 0.005). Moreover, in univariate and multivariate analyses (adjusted to Fuhrman grade and tumor stage), Piwi-like 1 positivity was associated with a shorter cancer-specific survival in the patients in the second cohort. In addition, Piwi-like 1 expression allowed to further distinguish the RCC patients with high Fuhrman grade, high tumor stage, distant metastasis or high pre-operative levels of C-reactive protein, as Piwi-like 1 positivity was associated with a shorter cancer-specific survival in both cohorts. Our data encourage further investigations to enlighten the role of Piwi-like 1 and its function as a marker of poor prognosis in RCC patients.

Effects of whole-body electromyostimulation combined with individualized nutritional support on body composition in patients with advanced cancer: a controlled pilot trial.

BACKGROUND: Physical exercise and nutritional treatment are promising measures to prevent muscle wasting that is frequently observed in advanced-stage cancer patients. However, conventional exercise is not always suitable for these patients due to physical weakness and therapeutic side effects. In this pilot study, we examined the effect of a combined approach of the novel training method whole-body electromyostimulation (WB-EMS) and individualized nutritional support on body composition with primary focus on skeletal muscle mass in advanced cancer patients under oncological treatment. METHODS: In a non-randomized controlled trial design patients (56.5% male; 59.9 ± 12.7 years) with advanced solid tumors (UICC III/IV, N = 131) undergoing anti-cancer therapy were allocated to a usual care control group (n = 35) receiving individualized nutritional support or to an intervention group (n = 96) that additionally performed a supervised physical exercise program in form of 20 min WB-EMS sessions (bipolar, 85 Hz) 2×/week for 12 weeks. The primary outcome of skeletal muscle mass and secondary outcomes of body composition, body weight and hand grip strength were measured at baseline, in weeks 4, 8 and 12 by bioelectrical impedance analysis and hand dynamometer. Effects of WB-EMS were estimated by linear mixed models. Secondary outcomes of physical function, hematological and blood chemistry parameters, quality of life and fatigue were assessed at baseline and week 12. Changes were analyzed by t-tests, Wilcoxon signed-rank or Mann-Whitney-U-tests. RESULTS: Twenty-four patients of the control and 58 of the WB-EMS group completed the 12-week trial. Patients of the WB-EMS group had a significantly higher skeletal muscle mass (0.53 kg [0.08, 0.98]; p = 0.022) and body weight (1.02 kg [0.05, 1.98]; p = 0.039) compared to controls at the end of intervention. WB-EMS also significantly improved physical function and performance status (p < 0.05). No significant differences of changes in quality of life, fatigue and blood parameters were detected between the study groups after 12 weeks. CONCLUSIONS: Supervised WB-EMS training is a safe strength training method and combined with nutritional support it shows promising effects against muscle wasting and on physical function in advanced-stage cancer patients undergoing treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT02293239 (Date: November 18, 2014).

Pembrolizumab monotherapy versus chemotherapy for treatment of advanced urothelial carcinoma with disease progression during or following platinum-containing chemotherapy. A Cochrane Rapid Review.

BACKGROUND: The use of systemic immunotherapy targets is emerging as an important treatment option for metastatic urothelial carcinoma, particularly for patients who cannot tolerate or who fail cisplatin-based chemotherapy. One such target is the inhibition of the checkpoint protein programmed cell death-1 (PD-1) receptor and its ligand (PD-L1) by monoclonal antibodies. OBJECTIVES: To assess the effects of pembrolizumab monotherapy versus chemotherapy for treatment of advanced urothelial carcinoma with disease progression during or following platinum-containing chemotherapy. SEARCH METHODS: We performed a Cochrane Rapid Review, limiting our search to published studies in the English language. We searched databases of the medical literature, including the Cochrane Central Register of Controlled Trials and MEDLINE, as well as trial registries including ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP). Our search extended from January 2000 to June 2018. SELECTION CRITERIA: We included randomised controlled trials except cross-over trials and cluster randomised trials. We excluded all other study designs. Participants included had locally advanced or metastatic urothelial carcinoma of the bladder, with disease progression during or following platinum-containing chemotherapy (synonymous with second-/third-/fourth-line therapy). This review focused on pembrolizumab (synonyms: MK-3475, lambrolizumab, Keytruda). DATA COLLECTION AND ANALYSIS: Two review authors independently classified and abstracted data from the included study. The certainty of evidence was rated according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: We identified one randomised controlled trial that included 542 participants, which compared the use of pembrolizumab monotherapy versus chemotherapy for the treatment of advanced urothelial carcinoma with disease progression during or following platinum-containing chemotherapy. Results were reported after a median follow-up of 14.1 months (range 9.9 to 22.1 months).Primary outcomesPembrolizumab probably reduces the risk of death from any cause (hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.59 to 0.90; moderate certainty evidence). This corresponds to 115 fewer deaths (191 fewer to 38 fewer) per 1000 participants with pembrolizumab at 12 months. We downgraded the certainty of evidence one level for imprecision.Pembrolizumab may slightly improve quality of life (change from baseline to week 15 assessed with the Core Quality of Life Questionnaire; higher value reflects better quality of life; scale 0 to 100) with a mean difference (MD) of 9.05, 95% CI 4.61 to 13.50; low certainty evidence). We downgraded the certainty of evidence two levels for study limitations and imprecision.Secondary outcomesPembrolizumab may have little or no effect on disease progression (HR 0.98, 95% CI 0.81 to 1.19; low certainty evidence). This corresponds to three fewer patients (42 fewer to 24 more) whose disease progressed per 1000 participants at 12 months. We downgraded the certainty of evidence two levels for study limitations and imprecision.Pembrolizumab probably improves treatment response (based on complete or partial radiologic response) with a risk ratio (RR) of 1.85, 95% CI 1.24 to 2.77; moderate certainty evidence). This corresponds to 97 more respondents (27 more to 202 more) per 1000 participants with pembrolizumab. We downgraded the certainty of evidence one level for imprecision.Pembrolizumab may have little or no effect on treatment-related mortality (RR 0.96, 95% CI 0.24 to 3.79; low certainty evidence). This corresponds to one fewer (12 fewer to 44 more) treatment-related deaths per 1000 participants with pembrolizumab. We downgraded the certainty of evidence two levels for study limitations and imprecision.Pembrolizumab may have little or no effect on discontinuations due to adverse events (RR 0.66, 95% CI 0.39 to 1.10). This corresponds to 54 fewer discontinuations per 1000 participants (95% CI 79 fewer to 7 more). We downgraded the certainty of evidence for study limitations and imprecision.Pembrolizumab may reduce serious adverse events (RR 0.83, 95 CI 0.72 to 0.97; low certainty evidence). This corresponds to 107 fewer serious averse events per 1000 participants (95% CI 19 fewer to 176 fewer). We downgraded two levels for study limitations and imprecision. AUTHORS' CONCLUSIONS: The use of pembrolizumab in men with advanced urothelial carcinoma with disease progression during or following platinum-containing chemotherapy probably improves overall survival when compared with chemotherapy alone. At 12 months follow-up about 70% of those in the chemotherapy group had died, compared with 59% of those treated with pembrolizumab. We are very uncertain about the effects of pembolizumab on quality of life. Pembolizumab may also improve treatment response rates, and reduce the risk of serious adverse events, but may make little or no difference to discontinuations of treatment due to adverse events. These conclusions are based on a single trial that was sponsored by the producer of pembrolizumab.

Immunohistochemiocal subtyping using CK20 and CK5 can identify urothelial carcinomas of the upper urinary tract with a poor prognosis.

PURPOSE: Genome-wide analyses revealed basal and luminal subtypes of urothelial carcinomas of the bladder. It is unknown if this subtyping can also be applied to upper tract urothelial carcinomas. MATERIALS AND METHODS: Tumor samples from 222 patients with upper tract urothelial carcinomas who were treated with radical nephroureterectomy were analyzed for the expression of seven basal/luminal immunohistochemical markers (CK5, EGFR, CD44, CK20, p63, GATA3, FOXA1). RESULTS: Hierarchical clustering revealed a basal-like subtype (enrichment of CK5, EGFR and CD44) in 23.9% and a luminal-like subtype (enrichment of CK20, GATA3, p63 and FOXA1) in 13.1% of the patients. In 60.8%, little to no markers were expressed, whereas markers of both subtypes were expressed in 2.2%. By using CK5 and CK20 as surrogate markers for the basal and luminal subtypes, we defined four subtypes of upper tract urothelial carcinomas: (i) exclusively CK20 positive and CK5 negative (CK20+/CK5-), (ii) exclusively CK5 positive and CK20 negative (CK20-/ CK5+), (iii) both markers positive (CK20+/CK5+) and (iv) both markers negative (CK20-/CK5-). A receiver-operator analysis provided the optimal cut-off values for this discrimination. An immunoreactive score >1 for CK5 and >6 for CK20 were defined as positive. In multivariate Cox's regression analysis, the CK20+/CK5- subtype was an independent negative prognostic marker with a 3.83-fold increased risk of cancer-specific death (p = 0.02) compared to the other three subtypes. CONCLUSIONS: Immunohistochemical subgrouping of upper tract urothelial carcinomas by analyzing CK5 and CK20 expression can be performed in a routine setting and can identify tumors with a significantly worse cancer-specific survival prognosis.

Preoperatively Dilated Ureters are a Specific Risk Factor for the Development of Ureteroenteric Strictures after Open Radical Cystectomy and Ileal Neobladder.

PURPOSE: We evaluated preoperative ureteral obstruction as a risk factor for benign ureteroenteric anastomosis strictures in patients who underwent open radical cystectomy and ileal neobladder diversion. MATERIALS AND METHODS: A total of 953 patients in whom bilateral ileoureterostomy was performed between January 1986 and March 2009 formed the study population. A nonrefluxing Le Duc technique was applied in 357 consecutive patients and a refluxing Wallace type technique was applied in 596. We defined ureteroenteric anastomosis stricture as the need for specific therapy (eg stenting, dilatation or reimplantation) or as proven loss of renal function. Kaplan-Meier analysis was done to calculate the likelihood of ureteroenteric anastomosis stricture development. RESULTS: Median followup in the study population was 65 months. Preoperatively 109 patients had unilateral or bilateral obstructed ureters. Unilateral or bilateral obstruction developed in 107 of the 953 patients (127 reno-ureteral units, including 63 on the right side and 64 on the left side). Of the reno-ureteral units 98 had benign and 29 had malignant ureteroenteric anastomosis strictures. The overall stricture rate due to any cause in preoperatively obstructed ureters was 19.3% at 10 years vs 6.4% in preoperatively undilated ureters. For the refluxing Wallace type technique the 10-year ureteroenteric anastomosis stricture rate was 2.4% for preoperatively undilated and 7.6% for preoperatively obstructed ureters. For the nonrefluxing technique the corresponding rates at 10 years were 14.2% and 35.54%, respectively. CONCLUSIONS: Preoperatively obstructed ureters are at significantly higher risk for benign ureteroenteric anastomosis strictures during the postoperative course after ileal neobladder diversion. Most such Le Duc strictures are bilateral and most such Wallace type strictures are unilateral. The risk of ureteroenteric anastomosis stricture after ureteroenterostomy using the nonrefluxing technique is threefold the risk of the refluxing technique. There was no preponderance of left ureteroenteric anastomosis strictures after each technique.