Robot-assisted versus open radical nephroureterectomy for urothelial carcinoma of the upper urinary tract: A retrospective cohort study across ten years.

PURPOSE: Radical nephroureterectomy is the gold standard of treatment for high-risk non-metastatic urothelial carcinoma of the upper urinary tract. However, the optimal surgical approach remains a controversial debate. This study compared the perioperative and oncological outcomes of open and robot-assisted radical nephroureterectomies. METHODS: 131 consecutive radical nephroureterectomies (66 robot-assisted nephroureterectomies vs. 65 open nephroureterectomies) for urothelial carcinoma of the upper urinary tract at a single tertiary referral center were included from 2009 to 2019. The perioperative and oncological outcomes were compared between both surgical approaches, including logistic regression analysis, propensity score matching, Kaplan Meier analyses, and Cox regression models. RESULTS: Overall, robot-assisted surgery had less blood loss (150 ml vs. 250, p = 0.004) and less positive surgical margins (1.5% vs. 15.4%, p = 0.004) at a comparable operating time (robotic 188min vs. 178). Any grade complications were more frequent after open surgery (40.9% vs. 63.1%, p = 0.011), and the length of stay was shorter after robotic nephroureterectomy (9 days vs. 12, p < 0.001). These differences remained significant in the propensity score matched analysis, except for the complication rates, which were still lower for the robotic approach, but no longer significant. At a median follow-up of 30.9 months (range 1.4-129.5), neither the progression-free survival (PFS, 2-year: robotic 66.7% vs. open 55.3%), nor the overall survival differed significantly (OS, 2-year: robotic 76.2% vs. open 68.4%). In the Cox regression, the surgical approach did not impact the PFS or OS. Lymph node metastases (HR 3.32, p = 0.008) had the strongest impact on the PFS besides patient age (HR 1.51 per 10 years, p = 0.025) and prior cystectomy (HR 2.42, p = 0.026) in the multivariate analysis. CONCLUSIONS: Robot-assisted radical nephroureterectomy had significant perioperative advantages at comparable oncological outcomes compared to open surgery for the treatment of urothelial carcinoma of the upper urinary tract at a high volume center, experienced in robotic surgery.

Preoperative positive voided urine cytology predicts poor clinical outcomes in patients with upper tract urothelial carcinoma undergoing nephroureterectomy.

BACKGROUND: Performance of urinary cytology is recommended as the part of a standard diagnostic workup and base surveillance regimens in upper tract urothelial carcinoma (UTUC). However, the effect of positive voided urine cytology (VUC) on UTUC prognosis, compared with negative VUC, has not been fully demonstrated. This study aimed to evaluate the impact of preoperative VUC on predicting intravesical recurrence, disease recurrence, and mortality in patients with UTUC who underwent nephroureterectomy (RNU). METHODS: Clinicopathological information was collected from 315 UTUC patients treated with RNU. The association between VUC and oncological outcomes was analyzed using the Kaplan-Meier method with log-rank test and Cox proportional hazards regression models. Multiple logistic regression analysis was performed to identify the influence of VUC on tumor grade. RESULTS: Preoperative positive VUC, presenting in 101 patients (32%), was significantly associated with tumor multifocality (P = 0.017) and higher tumor grade (P = 0.010). On multivariable Cox regression analyses, preoperative positive VUC was an independent prognostic factor of intravesical recurrence-free survival (RFS) (hazard ratio [HR] = 2.21, 95% confidence interval [CI] 1.06-4.64; P = 0.035), RFS (HR = 1.80, 95% CI 1.08-2.99; P = 0.023), and cancer-specific survival (CSS) (HR = 1.87, 95% CI 1.10-3.18; P = 0.020), but not overall survival (HR = 1.32, 95% CI 0.80-2.18; P = 0.28). Logistic regression analysis revealed that VUC was related to high tumor grade in UTUC (odds ratio = 2.23, 95%CI 1.15-4.52). CONCLUSION: Preoperative positive VUC significantly increases the risk of intravesical recurrence in UTUC patients undergoing RNU. In addition, positive VUC is an adverse predictor of RFS and CSS, which might be due to the association between positive VUC and high tumor grade.

Combination of Platelet-Lymphocyte Ratio and Monocyte-Lymphocyte Ratio as a New Promising Prognostic Factor in Upper Tract Urothelial Carcinoma With Large Tumor Sizes > 3 cm.

PURPOSE: The purpose of this study was to evaluate the prognostic values of pathological tumor size and preoperative blood-based inflammation biomarkers, including the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR), in upper tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: From 2007 to 2017, retrospective data of 449 patients with UTUC who underwent radical nephroureterectomy were assessed. Use of Kaplan-Meier and univariable/multivariable analyses evaluated the effect of preoperative blood-based inflammation biomarkers on overall (OS), cancer-specific (CSS), and progression-free survival (PFS) in pathological tumor sizes > and ≤3 cm. RESULTS: Kaplan-Meier analyses showed that high-level NLR, PLR, or MLR had significantly shorter OS, CSS, and PFS for tumor sizes >3 cm (all P < .05), but not for ≤3 cm. For UTUCs with tumor sizes >3 cm, multivariable analyses showed simultaneously high-level PLR and MLR to be independent predicators of poor OS, CSS, and PFS (all P < .05). Moreover, receiver operating characteristic (ROC) analyses revealed that the predictive accuracy of the combination of PLR and MLR for OS, CSS, and PFS with the area under the ROC curve of 0.836, 0.871, and 0.806, respectively, in tumor sizes >3 cm (all P < .001). CONCLUSIONS: Our study demonstrated that a high-level PLR and MLR can serve as an independent predicator of worse outcomes in UTUCs with tumor sizes >3 cm. This combination can clinically help enhance the prognostic discrimination of UTUCs with tumor sizes >3 cm and further may guide physicians in selecting patients for postoperatively systemic chemotherapy.

Contemporary conditional cancer-specific survival after radical nephroureterectomy in patients with nonmetastatic urothelial carcinoma of upper urinary tract.

BACKGROUND AND OBJECTIVES: To examine the effect of conditional survival on 5-year cancer-specific survival (CSS) probability after radical nephroureterectomy (RNU) in a contemporary cohort of patients with non-metastatic urothelial carcinoma of the upper urinary tract (UTUC). METHODS: Within the Surveillance, Epidemiology and End Results database (2004-2015), 6826 patients were identified. Conditional 5-year CSS estimates were assessed after event-free follow-up duration. Multivariable Cox regression (MCR) models predicted cancer-specific mortality (CSM) according to event-free follow-up length. RESULTS: Overall, 956 (14.0%) were T1 low grade(LG)N0 , 1305 (19.1%) T1 high grade(HG)N0 , 1215 (17.8%) T2 N0 , 2249 (32.9%) T3 N0 and 1101 (16.1%) T4 N0 /Tany N1-3 . From baseline, 93.4% to 94.2% in T1 LGN0 provided 5-year CSS and, respectively, 86.2% to 95.3% in T1 HGN0 , 77.5% to 87.8% in T2 N0 , 63.0% to 91.1% in T3 N0 , and 38.8% to 88.2% in T4 N0 /Tany N1-3 . In MCR models, relative to T1 LGN0 , T1 HGN0 (Hazard ratio [HR] 1.7), T2 N0 (HR 3.0), T3 N0 (HR: 5.2), and T4 N0 /Tany N1-3 (HR 11.9) were independent predictors of higher CSM. Conditional HRs decreased to levels equivalent to T1 LGN0 at 3 years vs 5 years of event-free survival for T1 HGN0 and all other groups, respectively. CONCLUSIONS: A direct relationship exists between event-free follow-up and survival probability after RNU. From a clinical perspective, such survival estimates may have particular importance during preoperative counseling.

Preoperative frailty predicts adverse short-term postoperative outcomes in patients treated with radical nephroureterectomy.

BACKGROUND: To investigate the effect of frailty on short-term postoperative outcomes and total hospital charges (THCs) in patients with non-metastatic upper urinary tract carcinoma, treated with radical nephroureterectomy (RNU). METHODS: Within the National Inpatient Sample (NIS) database we identified 11 258 RNU patients (2000-2015). We used the Johns Hopkins frailty-indicator to stratify patients according to frailty status. Time trends and multivariable logistic, Poisson and linear regression models were applied. RESULTS: Overall, 1801 (16.0%) patients were frail, 4664 (41.4%) were older than 75 years and 1530 (13.6%) had Charlson comorbidity index ≥2. Rates of frail patients increased over time, from 7.3% to 24.9% (P < .001). Frail patients exhibited higher rates (all P < .05) of overall complications (62.6% vs 50.9%), in-hospital mortality (1.6% vs 1.0%), non-home-based discharge (22.7% vs 12.1%), longer length of stay (LOS) (6 vs 1 day) and higher THCs ($49 539 vs $39 644). Moreover, frailty independently predicted (all P < .05) overall complications (OR, 1.46), in-hospital mortality (OR, 1.52), non-home-based discharge (OR, 1.36), longer LOS (RR, 1.30) and higher THCs (RR, +$11 806). CONCLUSION: Preoperative frailty is important in RNU patients. One of four RNU patients is frail. Moreover, frailty predicts short-term postoperative complications, as well as longer LOS and higher THCs after RNU.

Preoperative hydronephrosis as a predictor of postnephroureterectomy survival in patients with upper tract urothelial carcinoma: a two-center study in Japan.

OBJECTIVE: To evaluate the predictive value of preoperative hydronephrosis for pathological outcome and prognosis in patients with upper tract urothelial carcinoma treated with nephroureterectomy. METHODS: 167 patients with UTUC treated with nephroureterectomy at our two institutions in Japan between 2002 and 2017 were retrospectively analyzed. Preoperative computed tomography scans were evaluated for the presence of ipsilateral hydronephrosis. Preoperative hydronephrosis's associations with pathological outcome and postnephroureterectomy survival were assessed. RESULTS: Ipsilateral hydronephrosis was present in 102 patients (61.1%). Preoperative hydronephrosis was not associated with higher pathological T stage (T3 or greater). Patients with preoperative hydronephrosis compared with patients without preoperative hydronephrosis had significantly worse recurrence-free survival (RFS) (5-year survival, 61.9% and 77.6%, respectively; p = 0.033), disease-specific survival (DSS) (5-year survival, 66.9% and 88.1%, respectively; p = 0.026), and overall survival (OS) (5-year survival, 54.5% and 80.6%, respectively; p = 0.030). A multivariate Cox regression model identified preoperative hydronephrosis and higher clinical T stage (T3 or greater) as an independent predictor of shorter RFS (p = 0.015 and 0.0009, respectively). We segregated the patients into three risk groups based on the number of these two prognostic factors: 0, favorable risk; 1, intermediate risk; 2, poor risk. The favorable-risk group had significantly better RFS (p = 0.0003), DFS (p = 0.0001), and OS (p = 0.0007) than the poor and intermediate-risk groups (RFS (p = 0.0011), DFS (p = 0.0017), and OS (p = 0.0043)). CONCLUSION: The presence of preoperative hydronephrosis was a significant risk factor affecting survival. Our risk classification based on preoperative hydronephrosis and clinical T stage may be helpful for patient counselling and decision-making before nephroureterectomy.

Effect of lymph node dissection on stage-specific survival in patients with upper urinary tract urothelial carcinoma treated with nephroureterectomy.

BACKGROUND: We aimed to estimate the stage-specific impact of lymph node dissection (LND) on survival for upper urinary tract urothelial carcinoma (UTUC) patients treated with nephroureterectomy (NU). METHODS: Overall, 7278 UTUC patients undergoing NU within the SEER database from 2004 to 2015 were identified. Kaplan-Meier plots illustrated overall survival (OS) and cancer-specific survival (CSS) rates according to LND status. Multivariable Cox regression analyses assessed the effect of LND on OS and CSS rates stratified by pathological tumor stage. RESULTS: LND was performed in 26.9% of patients, and in 18.6, 23.3, 31.2 and 45.9% for pT1, pT2, pT3 and pT4 patients, respectively (P <  0.001). In multivariable Cox regression analyses, LND was associated with a higher OS or CSS in UTUC patients with pT3 and pT4 disease (all P <  0.05), but failed to achieve independent predictor status in patients with pT1 and pT2 disease (all P > 0.05). LND with 1 to 3 regional lymph nodes removed was prone to a higher OS or CSS only in pT4 compared to no LND (both P <  0.01). LND with 4 or more regional lymph nodes removed predisposed to a higher OS or CSS in pT3 or pT4 (all P <  0.05). CONCLUSIONS: The beneficial effect of LND especially LND with 4 or more regional lymph nodes removed on survival was evident in pT3/4 patients. LND can be considered for pT3 and pT4, for pT1/2 remains to be seen, both of which will be verified by further prospective studies.

Association between lymphovascular invasion and oncologic outcomes among upper urinary tract urothelial carcinoma patients who underwent radical nephroureterectomy.

PURPOSE: To determine the association between lymphovascular invasion (LVI) and upper tract urothelial carcinoma (UTUC) among patients who underwent radical nephroureterectomy (RNU). MATERIALS AND METHODS: From 2003 and 2018, retrospective data of 453 patients treated for UTUC with open, laparoscopic, or robotic RNU were collected. Pathological specimens were assessed for LVI through hematoxylin and eosin staining. According to presence of LVI, patients were stratified into two groups and compared for perioperative characteristics. Kaplan-Meier analysis was used to assess progression-free (PFS), cancer-specific (CSS), and overall survival (OS). Uni- and multivariate Cox regression models were used to find significance of LVI to survival. RESULTS: LVI was present in 132 (29.1%) of patients and was associated with higher age and lower preoperative GFR. Pathological outcomes included significantly higher tumor grade, higher rates of lymph node invasion and more positive surgical margins. During median 23.2 months follow-up (mean 37.1 months), 59.2% (n = 268) of total patients had tumor recurrence, with highest incidences in lymph nodes (51.5%). 5-year PFS, CSS, and OS were estimated at 35.4%, 94.6%, and 91.1% in LVI-negative patients and 17.2%, 75.1%, and 70.8% in LVI-positive patients, respectively (all p < 0.001). Multivariate analysis showed LVI to be an independent predictor of PFS (HR = 1.480; p = 0.018). CONCLUSION: LVI is an independent predictor of adverse PFS and is associated with poor CSS and OS in patients undergoing RNU for UTUC. These results may guide clinicians in selecting patients for adjuvant chemotherapy. Future prospective trials are necessary to further validate our results.

Long-Term Oncologic Outcomes of Laparoscopic Versus Open Radical Nephroureterectomy for Patients with T3N0M0 Upper Tract Urothelial Carcinoma: A Multicenter Cohort Study with Adjustment by Propensity Score Matching.

BACKGROUND: This study aimed to investigate the long-term oncologic outcomes of laparoscopic radical nephroureterectomy (LRNU) and open radical nephroureterectomy (ORNU) for patients with clinical and pathologic T3N0M0 upper tract urothelial carcinoma (UTUC). METHODS: Among 375 UTUC patients who underwent radical nephroureterectomy, this study identified 144 pT3N0M0 patients as cohort 1 after propensity score (PS) matching. Among 399 UTUC patients, the study identified 110 cT3N0M0 patients as cohort 2 after PS matching. Oncologic outcomes such as intravesical recurrence-free survival (IVRFS) and cancer-specific survival (CSS) were assessed by multivariate Cox's regression analysis. RESULTS: Cohort 1 of pT3N0M0 UTUC had 3-year CSS and IVRFS rates of 67.9 and 52.7%, respectively, in the LRNU group, which were significantly lower than in the ORNU group (81.4%, p = 0.039 and 71.6%, p = 0.046). The multivariate Cox's regression analysis identified the type of surgical approach (LRNU vs. ORNU) as one of the independent prognostic factors for CSS (hazard rate [HR], 1.88, p = 0.043) and IVRFS (HR, 1.75, p = 0.049). Cohort 2 of cT3N0M0 UTUC had 3-year CSS and IVRFS rates of 48.5 and 41.4%, respectively, in the LRNU group, which were significantly lower than in the ORNU group (65.8%, p = 0.049 and 67.2%, p = 0.047), and the type of surgical approach (LRNU vs. ORNU) remained as one of the independent prognostic factors for CSS and IVRFS. CONCLUSIONS: Based on clinical and pathologic T3N0M0 UTUC populations after PS adjustments, LRNU resulted in poorer CSS and IVRFS than ORNU.

Effect of neoadjuvant chemotherapy on locally advanced upper tract urothelial carcinoma: A systematic review and meta-analysis.

BACKGROUND: The role of neoadjuvant chemotherapy (NAC) for the management of upper tract urothelial carcinoma (UTUC) remains controversial. The aim of present study was to evaluate the contemporary role of NAC for patients with locally advanced UTUC through systematic review and meta-analysis of the literature. METHODS: Systematic literature searches were conducted in PubMed/Medline and Embase for all studies that examined the role of chemotherapy for UTUC. We performed this study according to the Preferred Reported Items for Systematic Reviews and Meta-analysis guidelines. Endpoints were overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). RESULTS: A total of four trials on 318 patients were included in this study. Each of the included studies was retrospective. Compared to controls, NAC improved OS, CSS, and PFS by 57% (95% confidence interval [CI], 0.25-0.73; p = 0.002), 59% (95% CI, 0.27-0.57; p < 0.00001), and 45% (95% CI, 0.50-0.60; p < 0.00001), respectively. The absolute increases in OS, CSS, and PFS were 11%, 18%, and 13%, respectively, and these increases are equivalent to numbers-needed-to-treat of 9, 5.5, and 7.6, respectively. Pooled odds ratio for the effect of NAC on downstaging was 0.21 (95% CI, 0.09-0.60; p = 0.004), which indicates that NAC group had a 4.76-fold higher probability of having pathologic N stage 0 than control group. CONCLUSIONS: NAC treatment before radical nephroureterectomy might provide better survival outcomes in patients with locally advanced UTUC. Prospective randomized studies are needed to confirm the benefits of NAC in locally advanced UTUC patients.

Incidence and survival outcomes in patients with upper urinary tract urothelial carcinoma diagnosed with variant histology and treated with nephroureterectomy.

OBJECTIVE: To evaluate the incidence and survival outcomes of histological variants of upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). MATERIALS AND METHODS: We retrospectively analysed data from 1610 patients treated with RNU for clinically non-metastatic UTUC between 1990 and 2016 in several centres participating in the UTUC Collaboration. Histological variants were classified as micropapillary, squamous, sarcomatoid and other, including other rare variants (<10 cases for each). Multivariable competing risk analyses were conducted to assess the effect of variant histology on overall recurrence and cancer-specific mortality (CSM). RESULTS: Overall, 1460 patients (91%) had pure urothelial carcinoma (PUC), whereas 150 (9%) were diagnosed with a variant histology, including 89 (5.0%), 41 (2.0%), 10 (1.0%) and 10 (1.0%) cases of micropapillary, squamous, sarcomatoid and other tumours, respectively. Variant histology was associated with the presence of adverse pathological features compared with PUC, including non-organ-confined disease (59% vs 38%; P < 0.001), lymph node invasion (28% vs 24%; P = 0.02), high-grade disease (88% vs 71%; P < 0.001), tumour necrosis (28% vs 16%; P = 0.001) and positive surgical margins (15% vs 8%; P = 0.01). In competing risk analysis, micropapillary variant was the only factor associated with worse recurrence (sub-hazard ratio [SHR] 2.27, 95% confidence interval [CI] 1.25-4.79; P = 0.02) whereas sarcomatoid variant was associated with worse CSM (SHR 16.8, 95% CI 6.86-41.17; P < 0.001). CONCLUSION: We found that one out of 10 patients with UTUC treated with RNU had variant histology. Only micropapillary and sarcomatoid variants were associated with poorer oncological outcomes after adjusting for available confounding factors.

The Comparison of Oncologic Outcomes between Open and Laparoscopic Radical Nephroureterectomy for the Treatment of Upper Tract Urothelial Carcinoma: A Korean Multicenter Collaborative Study.

PURPOSE: We compared oncologic outcomes of patients with upper tract urothelial carcinoma (UTUC) who underwent open nephroureterectomy (ONU) or laparoscopic nephroureterectomy (LNU). MATERIALS AND METHODS: Consecutive cases of ONU and LNU between 2000 and 2012 at five participating institutions were included in this retrospective analysis. Clinical characteristics and pathologic outcomes were compared between the two surgical approaches. The influence of the type of surgical approach on intravesical recurrence-free survival (IVRFS), progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS) was analyzed using the Kaplan-Meier method and differences were assessed with the log-rank test. Predictors of IVRFS, PFS, CSS, and OS were also analyzed with a multivariable Cox regression model. RESULTS: A total of 1,521 patients with UTUC were eligible for the present study (ONU, 906; LNU, 615). The estimated 5-year IVRFS (57.8 vs. 51.0%, p=0.010), CSS (80.4 vs. 76.4%, p=0.032), and OS (75.8 vs. 71.4%, p=0.026) rates were significantly different between the two groups in favor of LNU. Moreover, in patients with locally advanced disease (pT3/pT4), the LNU group showed better 5-year IVRFS (62.9 vs. 54.1%, p=0.038), CSS (64.3 vs. 56.9%, p=0.022), and OS (60.4 vs. 53.1%, p=0.018) rates than the ONU group. Multivariable Cox regression analyses showed that type of surgical approach was independently associated with IVRFS, but was not related to PFS, CSS, and OS. CONCLUSION: Our findings indicate that LNU provided better oncologic control of IVRFS, CSS, and OS compared with ONU for the management of patients with UTUC.

Laparoscopic versus open nephroureterectomy for upper urinary tract urothelial carcinoma: A systematic review and meta-analysis.

PURPOSE: To evaluate the efficacy and safety of laparoscopic nephroureterectomy (LNU) and open nephroureterectomy (ONU) for the treatment of upper urinary tract urothelial carcinoma (UTUC). METHODS: PubMed, Embase, and Cochrane databases were selected for systematic review of trials that compared outcomes of LNU and ONU. Meta-analysis was performed using RevMan 5.3 and STATA 13.0 software. RESULTS: LNU was associated with longer operation time (P < .001), shorter hospital stay (P < .001), less blood loss (P = .006) and lower rate of transfusion (P < .001). The occurrence of complications, including minor (P = .52), major (P = .21) and total complications (P = .19) were similar between LNU and ONU. There was no significant difference in the rate of 5-year recurrence-free survival (P = .90), 5-year cancer-specific survival (P = .12), and 5-year overall survival (P = .11) as well as 2-year RFS (P = .84), 2-year CSS (P = .86), and 2-year OS (P = .25). CONCLUSION: Our results indicated that LNU is a safe and effective method to treat UTUC. Given the limitations of this study, further multicenter, randomized trials are required to confirm these findings.

Prognostic impact of preoperative anemia on upper tract urothelial carcinoma.

The aim of this study was to investigate the effect of preoperative anemia on the prognosis of patients who underwent radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC).A total of 620 patients with UTUC were retrospectively analyzed. Anemia was decided by preoperatively measured hemoglobin values based on the World Health Organization (WHO) classification. Kaplan-Meier method and Cox proportional hazards regression models were used to analyze the relationship between anemia and survival outcomes. The meta-analysis part was performed according to PRISMA guidelines.The median follow-up was 51 (range: 1-168) months. A total of 246 patients had preoperative anemia in our cohort. Anemia was found to be related to high-grade (P < .001), sessile architecture (P = .001), advanced T stage (P < .001), lymphovascular invasion (LVI) (P = .006), and worse chronic kidney disease (CKD) stage (P = .012). Kaplan-Meier curves revealed that patients with preoperative anemia had worse overall survival (OS), cancer-specific survival (CSS), and disease recurrence-free survival (RFS) (all P < .001). Multivariable Cox analyses found that anemia was an independent predictor of CSS [hazard ratio (HR) 1.719, 95% confidence interval (95% CI): 1.285-2.300], RFS (HR 1.427, 95% CI: 1.114-1.829) and OS (HR 1.756, 95% CI: 1.353-2.279). Among patients without end-stage renal disease (ESRD, n = 614), the anemia was also proved to be associated with worse outcomes in multivariable Cox analysis (OS, HR 1.759, 95% CI: 1.353-2.287; CSS, HR 1.726, 95% CI: 1.289-2.311, and RFS, HR 1.431, 95% CI: 1.117-1.837). Seven studies were included in the meta-analysis, and the pooled results showed that anemia was also related to worse CSS (HR 2.05, 95% CI: 1.73-2.44), RFS (HR 1.57, 95% CI: 1.30-1.90), and OS (HR 1.53, 95% CI: 1.10-2.13), but not related to intravesical recurrence (HR 1.17, 95% CI: 0.75-1.82).Preoperative anemia was proved to be significantly associated with worse oncologic outcomes in patients with UTUC following RNU.

Multi-institutional evaluation of the prognostic significance of EZH2 expression in high-grade upper tract urothelial carcinoma.

PURPOSE: Enhancer of zeste homolog 2 is a methyltransferase encoded by the EZH2 gene, whose role in upper tract urothelial carcinoma (UTUC) is poorly understood. We sought to evaluate the prognostic value of EZH2 expression in UTUC. METHODS: We reviewed a multi-institutional cohort of patients who underwent radical nephroureterectomy for high-grade UTUC from 1990 to 2008. Immunohistochemistry for EZH2 was performed on tissue microarrays. Percentage of staining was evaluated, and the discriminative value of EZH2 was tested, with EZH2 positivity defined as>20% staining present. Clinicopathologic characteristics and oncologic outcomes (recurrence-free (RFS), cancer-specific (CSS), and overall survival (OS)) were compared, stratified by EZH2 positivity. The prognostic role of EZH2 was assessed using Kaplan-Meier, univariate (UVA), and multivariate (MVA) Cox regression analyses. Significance was defined for P<0.05. RESULTS: A total of 376 patients were included for analysis, with median follow-up 36.0 months. Overall, 78 (20.7%) were EZH2-positive. EZH2 expression was more often associated with ureteral location, lymphovascular invasion, sessile architecture, necrosis, and concomitant carcinoma in situ. On UVA, increased EZH2 expression was a significant predictor for inferior RFS (HR 1.63, P = 0.033), CSS (HR 2.03, P = 0.003), and OS (HR 2.11, P<0.001). On MVA EZH2 remained a significant predictor of worse CSS (HR 1.99 [95% CI: 1.21-3.27], P = 0.007) and OS (HR 1.54 [95% CI: 1.06-2.24], P = 0.024), while significance was lost for RFS. CONCLUSION: Increased EZH2 expression is associated with adverse pathologic features and inferior oncologic outcomes in patients with high-grade UTUC. The role of EZH2 biology in UTUC pathogenesis remains to be further elucidated.

Effect of Malnutrition on Radical Nephroureterectomy Morbidity and Mortality: Opportunity for Preoperative Optimization.

INTRODUCTION: Nutritional status has been increasingly recognized as an important predictor of prognosis and surgical outcomes for cancer patients. We evaluated the effect of preoperative malnutrition on the development of surgical complications and mortality after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: Using data from the American College of Surgeons National Surgical Quality Improvement Program, we evaluated the association of poor nutritional status with 30-day postoperative complications and overall mortality after RNU from 2005 to 2015. The preoperative variables suggestive of poor nutritional status included hypoalbuminemia (< 3.5 g/dL), weight loss within 6 months before surgery (> 10%), and a low body mass index. RESULTS: A total of 1200 patients were identified who had undergone RNU for UTUC. The overall complication rate was 20.5% (n = 246), and mortality rate was 1.75% (n = 21). On univariate analysis, patients who experienced a postoperative complication were more likely to have hypoalbuminemia (25.0% vs. 11.4%; P < .001) and weight loss (3.7% vs. 1.0%; P = .003). After controlling for baseline characteristics and comorbidities, hypoalbuminemia was found to be a significant independent predictor of postoperative complications (odds ratio, 2.09; 95% confidence interval, 1.29-3.38; P = .003). Hypoalbuminemia was also a significant independent predictor of mortality (odds ratio, 4.31; 95% confidence interval, 1.45-12.79; P = .008) on multivariable regression analysis. CONCLUSION: Our results have shown that hypoalbuminemia is a significant predictor of surgical complications and mortality after RNU for UTUC. This finding supports the importance of patients' preoperative nutritional status in this population and suggests that effective nutritional interventions in the preoperative setting could improve patient outcomes.

Oncologic outcomes for open and laparoscopic radical nephroureterectomy in patients with upper tract urothelial carcinoma.

BACKGROUND: Oncologic benefits of laparoscopic radical nephroureterectomy (LNU) are unclear. We aimed to evaluate the impact of surgical approach for radical nephroureterectomy on oncologic outcomes in patients with locally advanced upper tract urothelial carcinoma (UTUC). METHODS: Of 426 patients who underwent radical nephroureterectomy at five medical centers between February 1995 and February 2017, we retrospectively investigated oncological outcomes in 229 with locally advanced UTUC (stages cT3-4 and/or cN+). The surgical approach was classified as open nephroureterectomy (ONU) or LNU, and oncologic outcomes, including intravesical recurrence-free survival (RFS), visceral RFS, cancer-specific survival (CSS), and overall survival (OS), were compared between the groups. The inverse probability of treatment weighting (IPTW)-adjusted Cox-regression analyses was performed to evaluate the impact of LNU on the prognosis. RESULTS: Of the 229 patients, 48 (21%) underwent LNU. There were significant differences in patient backgrounds, including preoperative renal function, lymph-node involvement, lymphovascular invasion, and surgical margins, between the groups. Before the background adjustment, intravesical RFS, visceral RFS, CSS, and OS were significantly inferior in the ONU group than in the LNU group. However, in the IPTW-adjusted Cox-regression analysis, no significant differences were observed in intravesical RFS (hazard ratio [HR], 0.65; P = 0.476), visceral RFS (HR, 0.46; P = 0.109), CSS (HR, 0.48; P = 0.233), and OS (HR, 0.40; P = 0.147). CONCLUSION: Surgical approaches were not independently associated with prognosis in patients with locally advanced UTUC.

Preoperative controlling nutritional status (CONUT) score as a novel predictive biomarker of survival in patients with localized urothelial carcinoma of the upper urinary tract treated with radical nephroureterectomy.

OBJECTIVE: The purpose of this study was to investigate the correlation between the controlling nutritional status (CONUT) score and survival of patients with localized urothelial carcinoma of the upper urinary tract treated with radical nephroureterectomy (RNU). METHODS AND MATERIALS: We retrospectively enrolled 107 patients. CONUT score was calculated based on the serum albumin concentration, lymphocyte count, and total cholesterol concentration. Patients were classified into 2 groups based on CONUT score. Relapse-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) after RNU were compared between the 2 groups, and predictors of survival were analyzed using Cox proportional hazards regression models. RESULTS: For CONUT score, the area under the curve was 0.588 and the optimal cutoff value was 3. Twenty-four patients (22.4%) had high CONUT scores. The patients with high CONUT scores had significantly shorter 5-year RFS, CSS, and OS than did those with low CONUT scores (RFS: 50.1% vs. 66.0%; CSS: 28.1% vs. 71.7%; OS: 26.4% vs. 66.8%; all P<0.05). Results of the multivariable analysis, after adjustment for factors such as pT stage, pN stage, tumor grade, presence of lymphovascular invasion, and C-reactive protein level, revealed that CONUT score was an independent predictor of CSS (hazard ratio [HR] = 5.44, P = 0.0016) and OS (HR = 2.90, P = 0.0214) and showed marginal significance for predicting RFS (HR = 2.26, P = 0.0581). CONCLUSIONS: Preoperative CONUT score helps predict survival in patients with localized urothelial carcinoma of the upper urinary tract treated with RNU.

Variant histology as a significant predictor of survival after radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma.

OBJECTIVES: To investigate the effect of variant histology (VH) on survival after radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma (UTUC) and the effect of adjuvant chemotherapy on the survival of patients with UTUC with VH. MATERIALS AND METHODS: A total of 452 patients who underwent radical nephroureterectomy for UTUC without neoadjuvant chemotherapy in our institution between 1991 and 2012 were retrospectively analyzed. We performed a comparative analysis between pure UTUC and UTUC with VH groups. The Kaplan-Meier method was used to calculate survival estimates for cancer-specific survival (CSS) and overall survival (OS), and log-rank test was used to conduct comparisons between the groups. Univariate and multivariate Cox-proportional hazard regression analyses were performed to evaluate significant variables associated with CSS and OS. RESULTS: UTUC with VH was present in 41 (9.1%) patients. UTUC with VH showed aggressive clinicopathological features in comparison with pure UTUC. The Kaplan-Meier curves showed significantly decreased 5-year CSS and OS (both, P<0.001) in UTUC with VH group. Multivariate analysis revealed that VH was an independent predictor of CSS (P<0.001) and OS (P<0.002). The Kaplan-Meier curves also showed significantly decreased 5-year CSS and OS in UTUC with the VH group compared to the pure UTUC group in patients who received adjuvant chemotherapy. CONCLUSIONS: We found that UTUC with VH harbored aggressive biologic features, and VH was an independent prognostic factor for CSS and OS on both univariate and multivariate analyses. In addition, UTUC with VH group had poorer survival outcomes than pure UTUC group in patients who received adjuvant chemotherapy. Consequently, adjuvant treatment modalities other than adjuvant chemotherapy should be considered in this group.