Interethnic differences in the impact of body mass index on upper tract urothelial carcinoma following radical nephroureterectomy.

PURPOSE: Inconsistent prognostic implications of body mass index (BMI) in upper tract urothelial carcinoma (UTUC) have been reported across different ethnicities. In this study, we aimed to analyze the oncologic role of BMI in Asian and Caucasian patients with UTUC. METHODS: We retrospectively collected data from 648 Asian Taiwanese and 213 Caucasian American patients who underwent radical nephroureterectomy for UTUC. We compared clinicopathologic features among groups categorized by different BMI. Kaplan-Meier method and Cox regression model were used to examine the impact of BMI on recurrence and survival by ethnicity. RESULTS: According to ethnicity-specific criteria, overweight and obesity were found in 151 (23.2%) and 215 (33.2%) Asians, and 79 (37.1%) and 78 (36.6%) Caucasians, respectively. No significant association between BMI and disease characteristics was detected in both ethnicities. On multivariate analysis, overweight and obese Asians had significantly lower recurrence than those with normal weight (HR 0.631, 95% CI 0.413-0.966; HR 0.695, 95% CI 0.493-0.981, respectively), and obesity was an independent prognostic factor for favorable cancer-specific and overall survival (HR 0.521, 95% CI 0.342-0.794; HR 0.545, 95% CI 0.386-0.769, respectively). There was no significant difference in outcomes among normal, overweight and obese Caucasians, but obese patients had a relatively poorer 5-year RFS, CSS, and OS rates of 52.8%, 60.5%, and 47.2%, compared to 54.9%, 69.1%, and 54.9% for normal weight patients. CONCLUSION: Higher BMI was associated with improved outcomes in Asian patients with UTUC. Interethnic differences could influence preoperative counseling or prediction modeling in patients with UTUC.

Hypertension is the primary component of metabolic syndrome associated with pathologic features of kidney cancer.

PURPOSE: To determine whether individual and/or cumulative components of metabolic syndrome (obesity, hypertension, dyslipidemia, and hyperglycemia) are associated with pathologic features of kidney cancer. PATIENTS AND METHODS: A review of our kidney tumor database identified 462 patients who underwent partial or radical nephrectomy for renal cell carcinoma. The NCEP ATP-III criteria were used to define metabolic syndrome (MetS). Linear fixed effects modeling and ordinal logistic regression examined the relationship between MetS (individual and cumulative components) and pathologic characteristics. RESULTS: Two hundred and seventy-eight men and 184 women with a median age of 58 years, BMI of 31 kg/m2, tumor size of 3.7 cm, and nephrometry score of 6 were included. Ninety-seven (21 %) patients met NCEP ATP-III criteria for MetS. Hypertension was the only individual component of MetS associated with pathologic features of kidney cancer including increased tumor size [geometric mean ratio 1.17 (1.05-1.32), P = 0.03], higher tumor grade [OR 1.49 (1.03-2.17), P = 0.04], increasing nephrometry score [OR 1.77 (1.28-2.48), P = 0.001], and non-clear cell histology [OR 1.42 (1.01-2.02), P = 0.05]. Furthermore, combinations of MetS components were associated with increased tumor grade (P = 0.02), tumor stage (P = 0.02), nephrometry score (P ≤ 0.001), and non-clear cell histology (P = 0.02), only when hypertension was included. CONCLUSION: MetS is composed of four risk factors each implicated in carcinogenesis. We identified hypertension as the primary component associated with specific pathologic features of kidney cancer. Further studies are necessary to elucidate whether the effect of hypertension is a function of severity and/or chronicity.

Hemostatic agent use during partial nephrectomy: trends, outcomes, and associated costs.

PURPOSE: To evaluate the ability of hemostatic agents (HA) to limit bleeding complications following partial nephrectomy (PN) and determine HA usage and costs as well as factors associated with post-operative bleeding complications. METHODS: The records of 429 PN performed for kidney cancers were reviewed for clinical, pathologic, and perioperative variables. Surgical approach, HA use, and HA expenditure were determined. Bleeding complications and management to 90 days after PN were annotated. Wilcoxon rank-sum and two-sample t tests identified factors associated with HA use. Univariate and limited multivariate logistic regression determined variables associated with bleeding complications. RESULTS: Use of HA was associated with longer OR duration, longer ischemia time, higher EBL, and method of PN (OPN and LPN > RPN) (all p values < 0.001). On bivariate analysis, while multiple factors were associated with bleeding complications, neither HA use (p = 0.924) nor the number of HA used (two agents vs one p = 0.712; three agents vs. one p = 0.606) were. A multivariable model noted that increasing RENAL score (p = 0.013) and surgical approach (OPN vs. RPN [p = 0.009] and LPN vs. RPN (p = 0.002]) were independently associated with bleeding complications, while HA use was not (p = 0.294). During the 16 years of analysis, a total of $77,687 USD was spent on HA. Average annual HA expenditure was $4855 USD with the peak being in 2010 where expense was $14,086. Mean annual costs for HA use were greater for OPN vs RAPN starting in 2013 (p = 0.02) CONCLUSIONS: The use of HA during PN was not associated with lower rates of bleeding complications. Therefore, judicious use in a case-specific manner is requisite to limit potentially unnecessary operative cost.

Pathologic stage as a surrogate for oncologic outcomes after receipt of neoadjuvant chemotherapy for high-grade upper tract urothelial carcinoma.

OBJECTIVE: Whether pathologic stage at radical nephroureterectomy (RNU) can serve as an appropriate surrogate for oncologic outcomes in patients with high-grade (HG) upper tract urothelial carcinoma (UTUC) treated with neoadjuvant chemotherapy (NAC) is not defined. We sought to determine whether patients who achieve pathologically non-muscle-invasive (ypT0, ypTa, ypT1, ypTis) HG UTUC after receipt of NAC exhibit oncologic outcomes comparable to those who are inherently low stage without chemotherapy. METHODS: We identified 647 UTUC patients who underwent RNU among 3 institutions from 1993to2016. Patients with low or unknown grade, pathologic muscle invasion, or receipt of adjuvant chemotherapy were excluded. We compared clinicopathologic data and oncologic outcomes between pT0-1 and ypT0-1 patients. Kaplan-Meier analysis was used to assess overall (OS), cancer-specific (CSS), and systemic recurrence-free (RFS) survival. Predictors of these endpoints were identified using Cox regression. RESULTS: 234 (43 ypT0-1, 191 pT0-1) patients with HG UTUC were included. Two patients exhibited pathologic complete response after NAC. OS (P = 0.055), CSS (P = 0.152), and RFS (P = 0.098) were similar between ypT0-1 and pT0-1 patients. Predictors of worse outcomes included African-American race (RFS, CSS, and OS), Charlson score (OS), and systemic recurrence (OS and CSS). CONCLUSIONS: Patients with HG UTUC who achieve ypT0-1 stage after NAC exhibit favorable oncologic outcomes comparable to those inherently non-muscle-invasive who do not receive chemotherapy. Improvements in clinical staging will play an important role in better defining candidacy for NAC in treating HG UTUC while minimizing overtreatment. Furthermore, pathologic stage may serve as an appropriate early surrogate for oncologic endpoints in designing clinical trials.

Intraoperative prophylactic intravesical chemotherapy to reduce bladder recurrence following radical nephroureterectomy.

PURPOSE: Single, postoperative instillation of prophylactic intravesical chemotherapy (pIVC) is effective in reducing bladder cancer recurrences following radical nephroureterectomy (RNU). Despite high level evidence, pIVC is underutilized. Intraoperative pIVC (I-pIVC) may be easier and safer to implement than postoperative pIVC (P-pIVC). We aimed to evaluate the efficacy of I-pIVC during RNU. MATERIALS AND METHODS: Retrospective analysis of patients undergoing RNU and I-pIVC or postoperative pIVC (P-pVC) with 20 to 40 mg mitomycin-C or 1 to 2 g gemcitabine. Recurrence rates were evaluated using the Kaplan-Meier curves and log rank test. Cox regression was used for univariable and multivariable analysis. RESULTS: One hundred and thirty-seven patients were included in the final analysis. 81% (111/137) had I-pIVC and 19% (26/137) had P-pIVC. In the I-pIVC group higher rates of HG, muscle invasive disease and gemcitabine use were observed. Overall, 74% (101/137) and 26% (36/137) had mitomycin-C and gemcitabine instillations, respectively. Within 12 months 14% (19/137) of the patients experienced bladder recurrence. Median time to bladder recurrence was 7 months (range 3-27). Twelve months bladder recurrence-free survival rates were 82% for the I-pIVC group, and 72% for the P-pIVC group ((log rank P = 0.365). CONCLUSIONS: I-pIVC during RNU may reduce bladder recurrence rates. Bladder recurrence rates are comparable to those reported using postoperative instillations. Intraoperative instillations may be easier to implement and may increase usage rates.

Validation of Hyponatremia as a Prognostic Predictor in Multiregional Upper Tract Urothelial Carcinoma.

Hyponatremia has been shown to be associated with prognosis in various cancers, but its role in upper tract urothelial carcinoma (UTUC) is largely unidentified. We created an international multiregional cohort of UTUC, consisting of 524 and 213 patients from Taiwan and the U.S., to validate the significance of hyponatremia. Clinicopathologic characteristics were compared according to the presence of hyponatremia. Univariate and multivariate Cox regression models were used to investigate the association of hyponatremia with disease progression and survival. The impact of hyponatremia in patients from distinct regions was also analyzed. Hyponatremia was found in 143 (19.4%) patients. Hyponatremic patients had significantly worse Eastern Cooperative Oncology Group (ECOG) performance status (p = 0.00001) and higher pT stage (p = 0.002). In multivariate analysis, hyponatremia was an independent prognostic factor for progression (HR 1.585, 95% CI 1.115-2.253, p = 0.010), cancer-specific death (HR 2.225, 95% CI 1.457-3.397, p = 0.0002), and overall mortality (HR 1.819, 95% CI 1.299-2.545, p = 0.0005). Kaplan-Meier analysis showed the consistent adverse effect of hyponatremia on all outcomes in patients from Taiwan and the U.S. (all p < 0.05). Hyponatremia is commonly accessible and can serve as a negative marker for both the general health condition and disease severity of UTUC patients. A similar implication of hyponatremia in progression and survival despite patients' region of presentation suggests its general applicability across different ethnicities.

Preoperative multiplex nomogram for prediction of high-risk nonorgan-confined upper-tract urothelial carcinoma.

BACKGROUND: Accurate risk stratification prior to radical nephroureterectomy remains a challenge with upper-tract urothelial carcinoma (UTUC). Herein, we generated an optimized preoperative tool predicting high-risk nonorgan-confined (NOC)-UTUC. MATERIALS AND METHODS: Retrospective evaluation of 699 patients undergoing radical nephroureterectomy at 3 academic centers. Multiplex preoperative patient, imaging, endoscopic, and laboratory values were evaluated. Model derivation and validation were based on a split-sample method. Patients were divided randomly into a development (training) cohort (70% of patients) and validation (test) cohort (30% of patients). Univariate and multivariate logistic regression addressed the prediction of NOC disease (pT3/pT4 and/or pN+) based on training cohort. A backward stepdown selection process achieved the most informative nomogram. The ROC analysis identified a cut-off point predicting high-risk disease. The test cohort served as "external" validation to verify the findings based on the training cohort. Bootstrap resampling was conducted for both internal and "external" validation to evaluate the model fitting. RESULTS: Total of 566 patients included for analysis, mean age 69.7 years, 85% Caucasian, 64% male, 62% high grade. NOC-UTUC was found in 184 (32.5%) patients on final pathology. Of 184 patients with NOC-UTUC, an equal number of renal pelvis and ureter only tumors (n = 74; 40.2% for each location) were noted; 36 (19.6%) had tumors in both locations. Multivariate model based on development cohort (n = 396) demonstrated clinical stage (odds ratio [OR] 14.0, P < 0.01), biopsy tumor grade (OR 3.3, P = 0.01), tumor architecture (OR 2.65, P = 0.09), and Hgb (OR 0.8, P = 0.02) level were independently associated with NOC disease. A preoperative nomogram incorporating these 4 variables achieved 82% accuracy, 48% sensitivity, and 95% specificity in predicting NOC-UTUC. The cut-off point for predicting high-risk disease was ≥0.49. CONCLUSIONS: We established and validated an accurate tool for the prediction of locally advanced NOC-UTUC. This preoperative nomogram can be used to more optimally select patients for preoperative systemic chemotherapy, and facilitate clinical trial enrollment.

Preoperative predictive model and nomogram for disease recurrence following radical nephroureterectomy for high grade upper tract urothelial carcinoma.

PURPOSE: To identify preoperative risk factors for disease recurrence, following radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), and to create a predictive nomogram. MATERIALS AND METHODS: Based on a multicenter database, we identified patients who underwent RNU due to high grade UTUC. Urothelial carcinoma of the bladder or contralateral UTUC was not considered as recurrence. Cox regression model was used to determine the effect of different preoperative variables as predictors of recurrence. RESULTS: Two hundred and forty-five patients were included in the analysis. The 2 and 5 years recurrence rates were 16.3% and 19.2%, respectively. Factors associated with recurrence on univariable analysis were sessile architecture hazard ratio (HR) 3.16 (95% CI, 1.38-7.26, P = 0.006), ≥cT3 disease HR 2.30 (95% CI, 1.12-4.72, P= 0.023), age >65 HR 2.02 (95% CI, 1.00-4.05, P= 0.048), Eastern Cooperative Group > 0 HR 1.98 (95% CI, 1.09-3.57, P= 0.023), hydronephrosis HR 1.93 (95% CI, 1.04-3.57, P= 0.035). Higher hemoglobin levels HR 0.81 (95% CI, 0.69-0.96, P= 0.013) and preoperative estimated glomerular filtration rate ≥ 50 HR 0.48 (95% CI, 0.25-0.92, P = 0.028) were associated with lower probability for recurrence. Multivariable analysis identified sessile architecture as the only independent predictor of recurrence HR 2.52 (95% CI, 1.09-5.86, P= 0.0308). C-index of 0.71 was calculated for a predictive model including all variables in the multivariable analysis, indicating good predictive accuracy. A nomogram predicting 2 and 5 year recurrence free probability was developed accordingly. CONCLUSIONS: Based on a multicenter database, we developed a nomogram with good predictive accuracy for recurrence following RNU. This may serve as an aid in decision-making regarding the use of neoadjuvant chemotherapy.

Impact of United States Preventive Services Task Force recommendations on prostate biopsy characteristics and disease presentation at a tertiary-care medical center.

BACKGROUND: To evaluate early consequences of 2012 United States Preventive Services Task Force (USPSTF) recommendations for decreased prostate-specific antigen (PSA) screening on prostate biopsy characteristics and prostate cancer presentation. MATERIALS AND METHODS: A single tertiary-care institution, multisurgeon, prospectively maintained database was queried for patients undergoing prostate biopsy from October 2005 to September 2016. Patient demographics, biopsy characteristics, and extent of disease were reported. Patient cohorts before and after USPSTF recommendations were compared using two-sample t test, Chi-square test, and Wilcoxon rank sum test with significance at P < 0.05. RESULTS: A total of 2,000 patients were analyzed, including 1,440 patients before and 560 patients after USPSTF recommendations. Following the recommendations, patients had higher prebiopsy PSA (5.90 vs. 6.70, P < 0.001). Overall, 817 (40.9%) patients had prostate cancer detected at biopsy with an increase from 37.0% before to 50.8% after (P < 0.001). Biopsies detected less low-risk Gleason ≤6 prostate cancer (47.4% vs. 41.1%) and more intermediate-risk Gleason 7 cancer (30.9% vs. 39.7%), with comparable findings of high-risk Gleason ≥8 cancer (21.7% vs. 19.2%), P = 0.042. In addition, greater percentage of core involvement (P < 0.001) was seen. At the time of diagnosis, extraprostatic extension identified by pelvic imaging increased from 12.6% to 18.9%, P = 0.039, with a trend toward lymph node positivity (1.1% vs. 2.2%, P = 0.078). Of those with metastatic disease, bony involvement occurred more often (1.7% vs. 3.2%, P = 0.041). CONCLUSIONS: After 2012 USPSTF guidelines, patients presented with higher PSA with prostate cancer were detected more frequently. More adverse, pathologic prostate cancer features were found on biopsy with the extent of disease implicating locally advanced/metastatic disease. These findings should be considered when counseling patients about prostate cancer screening importance.

Preoperative predictors of nonorgan-confined disease in upper-tract urothelial carcinoma differ between China and the United States.

OBJECTIVE: To compare preoperative predictors of nonorgan-confined (NOC) disease in patients with upper-tract urothelial carcinoma (UTUC) from the United States (US) and China. METHODS: Clinicopathologic data of patients with UTUC treated surgically at tertiary care facilities in the US or China from 1998 to 2015 were, retrospectively, compiled. Patient characteristics, preoperative imaging, cytology, ureteroscopic findings, and serum markers (neutrophil-to-lymphocyte ratio, estimated glomerular filtration rate, hemoglobin, and albumin) were evaluated. After excluding patients who received neoadjuvant chemotherapy, rates of NOC disease at definitive surgery were tabulated. Logistic regression and receiver operating characteristic analyses were performed to determine predictors of NOC for each country using previously published nomograms, and the cohorts were compared. RESULTS: Totally, 753 patients with UTUC were included for analysis (451 Chinese and 302 US). NOC rates were similar between the 2 countries (31% vs. 29%, P = 0.568). On multivariable analysis, cT3 stage (P = 0.001) and high-grade pathology on ureteroscopy (P = 0.011) were significant predictors for NOC in the US, while male gender (P = 0.034), tumor location on imaging (P = 0.009), tumor size on imaging (P = 0.044), neutrophil-to-lymphocyte (P = 0.043), and preoperative estimated glomerular filtration rate (P = 0.028) were significant in China. Areas under the curve differed by nomogram used (Western model: 0.750 in US, vs. 0.670 in China; Chinese model: 0.763 in US, vs. 0.828 in China). CONCLUSION: Predictors for NOC in UTUC differ between the US and China. There may be unique population-based markers that more profoundly influence the accuracy of nomograms in certain populations. Our findings highlight the importance of considering population differences when clinically applying predictive tools in UTUC.

Predicting morbidity after robotic partial nephrectomy: The effect of tumor, environment, and patient-related factors.

PURPOSE: To investigate the effect of tumor and nontumor related parameters on perioperative outcomes of robotic partial nephrectomy (RPN). PATIENTS AND METHODS: Patients who underwent RPN for a localized renal tumor at 2 institutions between June 2010 and November 2016 were reviewed. RENAL and Mayo adhesive probability (MAP) scores were calculated and information on comorbid conditions including ASA score, performance status, Charlson's comorbidity index (CCI), and history of cardiovascular disease was collected. Correlations between each variable and warm ischemia time, estimated blood loss (EBL), operative time, change in estimated glomerular filtration rate, and length of hospital stay were assessed. Logistic regression analyses were performed to identify the best predictors of overall complications, major complications, risk of conversion, and Trifecta achievement. RESULTS: A total of 500 patients were included. RENAL score was found to have a statistically significant (P<0.05) correlation with warm ischemia time, EBL, and change in estimated glomerular filtration rate. MAP score showed significant association (P<0.05) with operative time and EBL. CCI had a significant correlation (P<0.05) with length of hospital stay and postoperative complications. In multivariable analyses, MAP score as a continuous variable (OR = 7.66; P<0.001) and MAP risk group stratification (OR = 3.29; P = 0.005) were independent predictors of the risk of conversion. Major complications were significantly associated with the cardiovascular disease in both univariable (OR = 2.35; P = 0.01) and multivariable analysis (OR = 4.52, P = 0.01). Finally, the MAP score as a continuous variable was an independent factor of Trifecta achievement (OR = 0.56; P = 0.04). CONCLUSION: Patients related factors were the most important determinants of postoperative complications after RPN. RENAL and MAP scores had some influence on intraoperative parameters.