Intravesical Recurrence-free Survival Research Articles

Prognostic Significance of Murine Double Minute 2 Expression in Tumor Cells in Upper Tract Urothelial Carcinoma: An Analysis of 341 Cases in a Large Chinese Center.

Aims: The prognostic significance of murine double minute 2 (MDM2) expression remains unknown in patients with upper tract urothelial carcinoma (UTUC). This study was designed to evaluate MDM2 expression and its association with clinicopathological characteristics and tumor outcomes in UTUC patients. Materials and Methods: Expression levels of MDM2 and p53 were determined by immunohistochemistry in a cohort of 341 UTUC patients. Associations of MDM2 and p53 expression levels with clinicopathological characteristics, disease-free survival (DFS), cancer-specific survival (CSS), and intravesical recurrence-free survival (IVRFS) were analyzed. Results: Nuclear expression of MDM2 and p53 were detected in the tumor cells of 129 (37.8%) and 203 (59.5%) patients, respectively. Decreased p53 expression was associated with positive MDM2 staining in tumor cells (p = 0.002). MDM2 expression was correlated with the exposure to aristolochic acids (p = 0.020), better preoperative renal function (p = 0.016), ureter location (p = 0.002), higher pathological T stage (p = 0.006), high tumor grade (p < 0.001), presence of glandular differentiation (p = 0.036), and sarcoma differentiation (p = 0.020). Kaplan-Meier analysis showed that positive MDM2 staining was associated with shorter CSS (p < 0.001), DFS (p < 0.001), and IVRFS (p = 0.020); MDM2+/p53- was associated with shorter CSS (p < 0.001) and DFS (p < 0.001), but not IVRFS (p = 0.145); while CSS, DFS, and IVRFS did not differ significantly between the p53+ and p53- patients (p = 0.307, 0.089, and 0.198, respectively). Multivariate analyses revealed that MDM2 expression in tumor cells independently predicted shorter CSS (p < 0.001; hazard ratio [HR] = 2.600; 95% confidence interval [CI]: 1.625-4.161) and DFS (p < 0.001; HR = 1.863; 95% CI: 1.314-2.641), excepting IVRFS (p = 0.092; HR = 1.590; 95% CI: 0.928-2.726). Conclusions: UTUC patients with elevated MDM2 expression may exhibit more aggressive biological features of the tumor and tend to have shorter CSS and DFS.

Intravesical Chemotherapy after Radical Nephroureterectomy for Primary Upper Tract Urothelial Carcinoma: A Systematic Review and Network Meta-Analysis.

The aim of this study was to determine the prophylactic effect of intravesical chemotherapy. Furthermore, it aimed to compare the efficacy of regimens on the prevention of bladder recurrence, after nephroureterectomy, for upper tract urothelial carcinoma by systematic review and network meta-analysis. A comprehensive literature search was conducted to search for studies published before 22 December 2016 using PubMed, Embase, and Scopus. All studies comparing nephroureterectomy alone with prophylactic intravesical chemotherapy after nephroureterectomy were included. The primary outcome was intravesical recurrence-free survival rate. In addition, we conducted indirect comparisons among regimens using network meta-analysis, as well as three randomized controlled trials (RCTs) on multicenter setting, and one large retrospective study with a total of 532 patients were analyzed. The pooled hazard ratio (HR) of bladder recurrence was 0.54 (95% CI: 0.38–0.76) in intravesical instillation patients. On network meta-analysis, pirarubicin was ranked the most effective regimen, while maintenance therapy of mitomycin C (MMC) with Ara-C and induction therapy of MMC were ranked as the second and third most effective regimens, respectively. Our study demonstrates that intravesical chemotherapy can prevent bladder recurrence in patients with upper tract urothelial carcinoma after nephroureterectomy. It also suggests that a single instillation of pirarubicin is the most efficacious intravesical regimen.

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.

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). 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. 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. Based on clinical and pathologic T3N0M0 UTUC populations after PS adjustments, LRNU resulted in poorer CSS and IVRFS than ORNU.

Identification of Significant Prognostic Tissue Markers Associated with Survival in Upper Urinary Tract Urothelial Carcinoma Patients Treated with Radical Nephroureterectomy: A Retrospective Immunohistochemical Analysis Using Tissue Microarray.

PurposeThe purpose of this study was to identify prognostic tissue markers for several survival outcomes after radical nephroureterectomy among patients with upper urinary tract urothelial carcinoma using tissue microarray and immunohistochemistry.Materials and MethodsRetrospectively, data of 162 non-metastatic patients with upper urinary tract urothelial carcinoma after radical nephroureterectomy between 2004 and 2016 were reviewed to determine intravesical recurrence-free survival (IVRFS), disease-free survival (DFS), and overall survival (OS). The expression of 27 tissue markers on a tissue microarray of radical nephroureterectomy samples and prognostic values of clinicopathological parameters were evaluated using immunohistochemistry and Cox proportional hazard models after adjusting for significant prognostic clinicopathological variables. The expression of all tissue markers was categorized into a binary group with continuous H-scores (0-300).ResultsMedian follow-up was 53.4 months (range, 3.6 to 176.5 months); and, 58 (35.8%), 48 (29.6%), and 19 (11.7%) bladder recurrence, disease progression, and all cause death, respectively, were identified. After adjusting for significant clinicopathological factors including intravesical instillation for bladder recurrence-free survival, pathologic T category and intravesical instillation for disease progression-free survival, and pathologic T category for OS (p < 0.05), IVRFS was associated with epithelial cadherin (hazard ratio [HR], 0.49), epidermal growth factor receptor/erythroblastosis oncogene B (c-erb) (HR, 2.59), and retinoblastoma protein loss (HR, 1.85); DFS was associated with cyclin D1 (HR, 2.16) and high-molecular-weight cytokeratin (HR, 0.42); OS was associated with E-cadherin (HR, 0.34) and programmed cell death 1 ligand (HR, 13.42) (p < 0.05).ConclusionSeveral significant tissue markers were associated with survival outcomes in upper urinary tract urothelial carcinoma patients treated with radical nephroureterectomy.

Effect of Intravesical Bacilli Calmette-Guerin Therapy After Second Transurethral Resection in Stage Ta T1 High-Grade Bladder Cancer.

To evaluate the efficacy of Bacilli Calmette-Guerin (BCG) induction instillation therapy after second transurethral resection (TUR) in stage Ta T1 high-grade bladder cancer. We performed a retrospective analysis of 49 consecutive new onset Ta T1 high-grade bladder cancer patients treated with second TUR at our affiliated institutions. Residual cancer rate, intravesical recurrence-free survival (RFS), and risk factors related to RFS were evaluated by univariate and multivariate Cox proportional hazard model analyses. Thirty-one patients received BCG therapy after the second TUR (BCG group), and 18 patients were treated with second TUR alone (no BCG group). There were statistically significant differences in the RFS rates between the two groups, (P = 0.037). BCG therapy was the only factor predictive of intravesical recurrence after second TUR in both univariate and multivariate analyses. After the second TUR, BCG therapy significantly decreased intravesical recurrence in the patients with residual tumors (P = 0.014). However, there was no significant difference in intravesical recurrence in the patients with no residual tumors between the two groups (P = 0.359). BCG therapy after second TUR significantly decreased intravesical recurrence of residual tumors found at the second TUR.

Segmental ureterectomy can be performed safely in patients with urothelial carcinoma of distal ureter.

We aimed to compare oncological outcomes by surgery type (segmental ureterectomy [SU] vs. radical nephroureterectomy [RNU]) in a large cohort of patients with upper tract urothelial carcinoma (UTUC) of the distal ureter. We performed a retrospective analysis of 219 patients with UTUC of the distal ureter among 931 patients with UTUC who underwent SU and RNU. Clinicopathological outcomes were evaluated. Cancer-specific survival (CSS), overall survival (OS), local recurrence-free survival (RFS), intravesical recurrence-free survival (IVRFS), contralateral recurrence-free survival, and distal metastasis-free survival were assessed by the Kaplan-Meier method and Cox regression, estimating hazard ratios (HR) and 95% confidence intervals (CIs). A total of 179 (81.7%) patients underwent RNU and 40 (18.3%) underwent SU: 85 males (47.5%) with RNU and 17 (42.5%) with SU (p=0.568). The median age with RNU and SU was 71 years (range 31-86) and 70 years (range 46-90), respectively (p=0.499). The T stage of the two groups did not differ (p=0.122), nor did mean tumour length (3.35±2.62 vs. 3.25±2.14; p=0.953), grade (p=0.075), tumour necrosis (p=0.634), or followup time (months) (58.1±8.1 vs. 63.7±3.4; p=0.462). The two groups did not differ in CSS (p=0.358) or OS (p=0.206), and surgery type did not predict CSS (HR 0.862; 95% CI 0.469-1.585; p=0.633) or OS (HR 0.764; 95% CI 0.419-1.392; p=0.379). Local RFS was higher with RNU than SU (96.2% vs. 86.0%; p=0.02), but the groups did not differ in IVRFS (p=0.661), contralateral RFS (p=0.183), or distant metastasis-free survival (p=0.078). On multivariate analysis, SU was associated with local RFS (HR 5.069; 95% CI 1.029-24.968; p=0.046) and distant metastasis-free survival (HR 6.497; 95% CI 1.196-35.283; p=0.03). Local RFS was lower with SU than RNU for patients with pT3-4 stage (p=0.006). Long-term oncological outcomes were equivalent with SU and RNU in patients with UTUC of the distal ureter. SU affected local recurrence survival, especially with advanced tumour stage, and distant metastasis survival.

The diagnostic ureteroscopy before radical nephroureterectomy in upper urinary tract urothelial carcinoma is not associated with higher intravesical recurrence

BackgroundTo clarify if diagnostic ureteroscopy (URS) before radical nephroureterectomy for patients with upper tract urothelial carcinoma (UTUC) will increase the risk of intravesical recurrence.MethodsFrom retrospective review of cohort at our institution, 502 patients with UTUC who underwent radical nephroureterectomy with bladder cuff excision were enrolled from 1990 to 2013. Cox proportional hazards model was used to analyze the overall survival (OS), disease-free survival (DFS), metastasis-free survival (MFS), and intravesical recurrence-free survival (IVRFS). The log-rank test was used for comparing survival curves. All potential risk factors were included in the multivariate Cox proportional hazards model to recognize independent predictors. From NHI database, we included patients of UTUC without bladder cancer history using population-based database in Taiwan from 1996 to 2013. In total, 3079 URS and 2634 non-URS patients with UTUC were identified. Univariate and multivariate Cox proportional hazards regressions were performed to measure the risk of IVRFS and all-cause mortality.ResultsFrom our database, the comparison of clinicopathological characteristics in UTUC patients between with URS biopsy group (URS+) (n = 206, 41%) and without URS biopsy group (URS−) (n = 296, 59%) was insignificantly different excluding surgical method. URS biopsy is not associated with worse OS (p = 0.720), DFS (p = 0.294), MFS (p = 0.808), and IVRFS (p = 0.560) by multivariate analysis. Only bladder cancer history is an independent significant factor to predict IVR (p < 0.001). The same result from NHI database, URS before radical surgery will not increase the risk of IVRFS [adjusted HR 1.136, 95% CI 1.00–1.30; P = 0.059] and OS [adjusted HR 0.919, 95% CI 0.82–1.04; P = 0.164].ConclusionsPreoperative URS manipulation is not associated with higher risk of IVRFS even in patients without bladder cancer history. Diagnostic URS is feasible to compensate the insufficient information of image in patients with UTUC.

A rational risk assessment for intravesical recurrence in primary low-grade Ta bladder cancer: A retrospective analysis of 245 cases.

The aim of the present study was to evaluate the prognostic impact of size and number of tumors in primary low-grade (LG) Ta bladder urothelial carcinoma (UC), and thus allow accurate risk stratification of low-risk non-muscle invasive bladder cancer (NMIBC). This study was a retrospective analysis of 245 patients with primary LG Ta UC of the urinary bladder who were treated with transurethral resection. Differences in intravesical recurrence-free survival (RFS) according to various cutoff values of tumor size and tumor number were calculated using Cox proportional hazards model. Median maximum size of tumor was 1.4 cm, and 153 patients (62.4%) had solitary tumors. Forty-nine patients experienced intravesical recurrence during a median 34 months of follow-up. Patients with solitary tumors had significantly longer RFS times compared with those with ≥8 tumors (P=0.003). Patients with larger tumors had significantly shorter RFS times for each cutoff value (P=0.01 for 1.0 cm, P<0.0001 for 1.5 and 2.0 cm, P=0.006 for 3.0 cm). On multivariate analysis, each cutoff value of tumor size was found to be a predictor of RFS; among them, the cutoff of 1.5 cm showed the strongest association (hazard ratio, 4.12; 95% confidence interval, 2.11-8.81; P<0.001). If we consider only lower risk NMIBC patients, such as primary LG Ta, the appropriate cutoff value of tumor size to predict intravesical recurrence might be 1.5 cm, but not 3.0 cm generally adopted in various guidelines. These findings suggest the need for rational risk assessment with consideration of the diversity of patients with NMIBC.

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

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). 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. 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). Surgical approaches were not independently associated with prognosis in patients with locally advanced UTUC.

Outcomes of subsequent non-muscle-invasive bladder cancer treated with intravesical Bacillus Calmette-Guérin after radical nephroureterectomy for upper urinary tract urothelial carcinoma.

To describe the clinicopathological characteristics and prognosis of subsequent non-muscle-invasive bladder cancer (NMIBC) after radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC), and particularly its response to intravesical Bacillus Calmette-Guérin (BCG). An observational study was conducted in 1463 patients with UTUC who had undergone RNU and in 1555 patients with primary NMIBC. Of the 1463 patients with UTUC, 256 (17%) subsequently developed NMIBC (UTUC-NMIBC group) and were available for the analysis. The clinicopathological background and outcomes, including intravesical recurrence-free survival and bladder progression-free survival, were compared between the patients with UTUC-NMIBC and the patients with primary NMIBC treated with intravesical BCG. Propensity score matching was performed to adjust for the potential differences in the backgrounds of the two groups. To validate the utility of the CUETO scoring model in the UTUC-NMIBC group, risk scores were calculated and compared with the published probabilities for recurrence and progression. Compared with the unadjusted primary NMIBC group (n = 352), the UTUC-NMIBC group (n = 75) were found to have a worse prognosis for intravesical recurrence and progression, before propensity score matching. After propensity score matching for potential confounding factors, however, a worse prognosis was observed only for intravesical recurrence. The validation test of the CUETO scoring model for the UTUC-NMIBC group showed a significant difference in the rate of intravesical recurrence and progression for the 0-4 and 5-6 score groups between the UTUC-NMIBC group and the CUETO risk table reference data. Compared with the primary NMIBC group, the UTUC-NMIBC group had a worse prognosis after intravesical BCG, especially with regard to intravesical recurrence. This suggests that patients with UTUC-NMIBC are inherently poor responders to BCG exposure. An optimal treatment strategy and risk scoring model to select patients for adjuvant intravesical BCG, chemotherapy or immediate radical cystectomy should be established.

Impact of ureteroscopy before radical nephroureterectomy for upper tract urothelial carcinomas on oncological outcomes: a meta-analysis.

To investigate whether ureteroscopy (URS) before radical nephroureterectomy (RNU) for upper tract urothelial carcinomas (UTUCs) has an impact on oncological outcomes. We performed a systematic literature search of PubMed, Web of Science, and EMBASE for citations published prior to September 2017 that described URS performed on patients with UTUC and conducted a standard meta-analysis on survival outcomes. Our meta-analysis included eight eligible studies containing 3975 patients. The results were as follows: cancer-specific survival (CSS; hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.59-0.99; P = 0.04), overall survival (OS; HR 0.76, 95% CI 0.48-1.21; P = 0.24), recurrence-free survival (RFS; HR 0.89, 95% CI 0.69-1.14; P = 0.37), metastasis-free survival (MFS; HR 1.06, 95% CI 0.82-1.36; P = 0.66), and intravesical recurrence-free survival (IRFS; HR 1.51, 95% CI 1.29-1.77; P < 0.001). When excluding previous bladder tumour history, the result for IRFS was a HR of 1.81 (95% CI 1.53-2.13; P < 0.001). This meta-analysis indicated that URS before RNU did not have a negative impact on CSS, OS, RFS, or MFS in patients with UTUC. However, patients were at higher risk of intravesical recurrence after RNU when they had undergone URS before RNU. Further studies are needed to assess the effects of post-URS intravesical chemotherapy on intravesical recurrence.

Validation of the Pretreatment Neutrophil-to-Lymphocyte Ratio as a Prognostic Factor in a Large Cohort of Chinese Patients with Upper Tract Urothelial Carcinoma.

Background:The pretreatment neutrophil-to-lymphocyte ratio (NLR) has been reported to be a prognostic factor in various types of carcinomas. The aim of this study was to investigate the prognostic value of pretreatment NLR in a large cohort of Chinese patients with upper tract urothelial carcinoma (UTUC).Methods:We retrospectively analyzed the medical data of 656 UTUC patients who underwent radical nephroureterectomy (RNU) from 2001 to 2011 at Peking University First Hospital. Receiver operating characteristic (ROC) curve analysis was performed to calculate the optimal cutoff point of pretreatment NLR. Uni- and multi-variate analyses were used to identify the prognostic factors for cancer-specific survival (CSS) and intravesical recurrence-free survival (IVRFS).Results:The optimal cutoff point of pretreatment NLR was 2.40 by ROC curves, by which patients with high NLR (NLR ≥2.40) and low NLR (NLR <2.40) accounted for 314 (47.9%) and 342 (52.1%) patients, respectively. Patients with a high pretreatment NLR tended to have high tumor grades (χ2 = 15.725, P < 0.001), high tumor stages (χ2 = 25.416, P < 0.001), tumor sizes >5 cm (χ2 = 8.213, P = 0.005), ipsilateral hydronephrosis (χ2 = 4.624, P = 0.033), and concomitant carcinoma in situ (CIS) (χ2 = 9.517, P = 0.003). A high pretreatment NLR (hazard ratio [HR] = 1.820, P = 0.001), main tumor diameter >5 cm (HR = 1.789, P = 0.009), lymph node metastasis (HR = 1.863, P = 0.024), and high tumor stage (HR = 1.745, P < 0.001) independently predicted poor CSS after surgery, while only concomitant carcinoma in situ (CIS) (HR = 2.164, P = 0.034), ureteroscopy before surgery (HR = 1.701, P = 0.015), and high tumor grade (HR = 1.645, P = 0.018) were independent predictors of IVRFS after RNU.Conclusions:The pretreatment NLR was related to some adverse clinicopathological features and was an independent predictor of CSS, although not IVRFS, in Chinese UTUC patients.

Preoperative chronic kidney disease predicts poor oncological outcomes after radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma.

ObjectiveTo evaluate the impact of preoperative chronic kidney disease (CKD) on oncological outcomes in patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy.MethodsA total of 426 patients who underwent radical nephroureterectomy at five medical centers between February 1995 and February 2017 were retrospectively examined. Oncological outcomes, including intravesical recurrence-free, visceral recurrence-free, cancer-specific, and overall survival rates (intravesical RFS, visceral RFS, CSS, and OS, respectively) stratified by preoperative CKD status (CKD vs. non-CKD) were investigated. Cox proportional hazards regression analysis was performed using inverse probability of treatment weighting (IPTW) to evaluate the impact of preoperative CKD on prognosis and a prognostic factor-based risk stratification nomogram was developed.ResultsOf the 426 patients, 250 (59%) were diagnosed with CKD before radical nephroureterectomy. Before the background adjustment, intravesical RFS, visceral RFS, CSS, and OS after radical nephroureterectomy were significantly shorter in the CKD group than in the non-CKD group. Background-adjusted IPTW analysis demonstrated that preoperative CKD was significantly associated with poor visceral RFS, CSS, and OS after radical nephroureterectomy. Intravesical RFS was not significantly associated with preoperative CKD. The nomogram for predicting 5-year visceral RFS and CSS probability demonstrated a significant correlation with actual visceral RFS and CSS (c-index = 0.85 and 0.83, respectively).ConclusionsUpper tract urothelial carcinoma patients with preoperative CKD had a significantly lower survival probability than those without CKD.

Predictors for Intravesical Recurrence Following Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: A National Multicenter Analysis

The purpose of this study was to identify the prognostic impact of intravesical recurrence (IVR) on oncologic outcomes and the clinicopathologic factors that predict IVR in patients who undergo radical nephroureterectomy (RNU) for upper tract urothelial carcinoma. Between January 2000 and December 2015, 760 patients with upper tract urothelial carcinoma underwent RNU at 5 institutions in Korea, and patient data were retrospectively collected. Clinicopathologic factors were analyzed for intravesical recurrence-free survival, cancer-specific survival (CSS), and overall survival (OS). Univariate and multivariate Cox proportional hazards regression models were used to test the clinicopathologic factors on IVR. Of the 760 patients, 231 (30.3%) patients experienced IVR within 10 months of the median interval between RNU and the first IVR. The overall estimated probabilities of 5-year CSS, intravesical recurrence-free survival, and OS were 84.2%, 63.8%, and 79.2%, respectively. No difference was noted in terms of CSS and OS between the patients who did or did not experience IVR. The multivariate Cox analysis showed an association between IVR and positive hydronephrosis, tumor size, positive preoperative urinary cytology, and ureterorenoscopy before RNU (all P< .05). However, a significantly decreased riskof IVR was associated with female gender, laparoscopic RNU, and receipt of adjuvant systemic chemotherapy (allP< .05). The occurrence of IVR following RNU did not affect CSS and OS. Patients with larger tumor size, preoperative hydronephrosis, positive preoperative urinary cytology, and ureterorenoscopy before RNU had a higher risk of IVR following RNU.

The Conditional Survival with Time of Intravesical Recurrence of Upper Tract Urothelial Carcinoma.

Since conditional survival analysis provides better estimates of survival time at each followup, we assessed changes in conditional intravesical recurrence-free survival rates after radical nephroureterectomy. We also sought to determine how the impact of well-known risk factors evolves with time, particularly in patients with localized upper tract urothelial carcinoma. We identified 364 patients with Ta-3N0M0 localized upper tract urothelial carcinoma who underwent open or laparoscopic radical nephroureterectomy at 1 of our 3 institutions. Conditional intravesical recurrence-free and cancer specific survival rates were calculated using the Kaplan-Meier method. The changing impact of parameters on intravesical recurrence with time was assessed by multivariate Cox regression analysis. Intravesical recurrence after radical nephroureterectomy was detected in 176 patients (48.4%) and 93 (25.5%) died of localized upper tract urothelial carcinoma. Five-year intravesical recurrence-free and cancer specific survival rates after surgery were 41.5% and 72.9%, respectively. Based on 1, 2, 3 and 4-year survivorship the 5-year conditional intravesical recurrence-free survival rate increased from 41.5% to 60.5%, 73.4%, 79.5% and 96.7%, respectively. The 5-year conditional cancer specific survival rate also improved from 72.9% to 78.4%, 85.4%, 90.9% and 95.5% at 1, 2, 3 and 4 years, respectively. The effects of well-known predictive factors on estimated conditional survival decreased with time for intravesical recurrence. In contrast, the impact of T2 or lower pathological stage and laparoscopic radical nephroureterectomy sustained statistical power with time. Conditional survival analysis revealed that the probability of intravesical recurrence-free survival increased with time in patients with localized Ta-3N0M0 upper tract urothelial carcinoma after radical nephroureterectomy. Patients with T2 or lower T stage who undergo laparoscopic radical nephroureterectomy may be recommended for longer followup to detect subsequent intravesical recurrence.

Efficacy of early ureteral ligation on prevention of intravesical recurrence after radical nephroureterectomy for upper urinary tract urothelial carcinoma: a prospective single-arm multicenter clinical trial.

The rate of intravesical recurrence after radical nephroureterectomy for upper urinary tract urothelial carcinoma is high. Seeding upper urinary tract urothelial carcinoma cells onto the damaged bladder wall is considered to be one of the causes of intravesical recurrence after radical nephroureterectomy. We evaluated the utility of early ureteral ligation in preventing the intravesical recurrence. This prospective single-arm clinical trial included patients who underwent radical nephroureterectomy for upper urinary tract urothelial carcinoma in the Tohoku Urological Evidence-Based Medicine Study Group between 2012 and 2013. Early ureteral ligation was defined as ligation of the ureter as quickly as possible after expanding the retroperitoneal space. A historical control was extracted from 454 patients who underwent radical nephroureterectomy in the same group, using propensity score-matched analysis. Intravesical recurrence-free survival rates were analyzed using Kaplan-Meier curves. Factors predicting intravesical recurrence were assessed using multivariate analyses. Seventy-four patients underwent early ureteral ligation. Seventeen (23%) patients had intravesical recurrence with a median follow-up period of 24 months. The 1- and 2-year intravesical recurrence-free survival rates in the early ureteral ligation group were 81% and 76%, and in the control group 75% and 63%, respectively (P = 0.160). In patients with renal pelvic cancer, the 1- and 2-year intravesical recurrence-free survival rates in the early ureteral ligation group were 89% and 86%, but in the control group 74% and 64%, respectively (P = 0.025). However, intravesical recurrence-free survival rates were similar in patients with ureteral cancer. Multivariate analyses of a subset of patients with renal pelvic cancer identified early ureteral ligation as an independent predictor of intravesical recurrence. Early ureteral ligation decreases the rate of intravesical recurrence after radical nephroureterectomy in patients with renal pelvic cancer. Thus, early ureteral ligation might help in prevention of intravesical recurrence for renal pelvic cancer.

MP78-01 IMPACT OF URETEROSCOPY BEFORE RADICAL NEPHROURETERECTOMY FOR UPPER TRACT UROTHELIAL CARCINOMAS ON ONCOLOGIC OUTCOMES: A META-ANALYSIS

Objectives To investigate whether ureteroscopy (URS) before radical nephroureterectomy (RNU) for upper tract urothelial carcinomas (UTUCs) has an impact on oncological outcomes. Patients and Methods We performed a systematic literature search of PubMed, Web of Science, and EMBASE for citations published prior to September 2017 that described URS performed on patients with UTUC and conducted a standard meta-analysis on survival outcomes. Results Our meta-analysis included eight eligible studies containing 3975 patients. The results were as follows: cancer-specific survival (CSS; hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.59-0.99; P = 0.04), overall survival (OS; HR 0.76, 95% CI 0.48-1.21; P = 0.24), recurrence-free survival (RFS; HR 0.89, 95% CI 0.69-1.14; P = 0.37), metastasis-free survival (MFS; HR 1.06, 95% CI 0.82-1.36; P = 0.66), and intravesical recurrence-free survival (IRFS; HR 1.51, 95% CI 1.29-1.77; P l 0.001). When excluding previous bladder tumour history, the result for IRFS was a HR of 1.81 (95% CI 1.53-2.13; P l 0.001). Conclusions This meta-analysis indicated that URS before RNU did not have a negative impact on CSS, OS, RFS, or MFS in patients with UTUC. However, patients were at higher risk of intravesical recurrence after RNU when they had undergone URS before RNU. Further studies are needed to assess the effects of post-URS intravesical chemotherapy on intravesical recurrence.

Laparoscopic versus open nephroureterectomy to treat localized and/or locally advanced upper tract urothelial carcinoma: oncological outcomes from a multicenter study

BackgroundMany studies have reported the oncological outcomes between open radical nephroureterectomy (ONU) and laparoscopic radical nephroureterectomy (LNU) of upper tract urothelial carcinoma (UTUC). However, few data have focused on the oncological outcomes of LNU in the subgroup of localized and/or locally advanced UTUC (T1–4/N0-X). The purpose of this study was to compare the oncological outcomes of LNU vs. ONU for the treatment in patients with T1–4/N0-X UTUC.MethodsWe collected and analyzed the data and clinical outcomes retrospectively for 265 patients who underwent radical nephroureterectomy for T1–4/N0-X UTUC between April 2000 and April 2013 at two Chinese tertiary hospitals. Survival was estimated using the Kaplan-Meier method. Cox’s proportional hazards model was used for univariate and multivariate analysis.ResultsThe mean patient age was 62.0 years and the median follow-up was 60.0 months. Of the 265 patients, 213 (80.4%) underwent conventional ONU, and 52 (19.6%) patients underwent LNU. The groups differed significantly in their presence of previous hydronephrosis, presence of previous bladder urothelial carcinoma, and management of distal ureter (P < 0.05). The predicted 5-year intravesical recurrence- free survival (RFS) (79% vs. 88%, P = 0.204), overall RFS (47% vs. 59%, P = 0.076), cancer-specific survival (CSS) (63% vs. 70%, P = 0.186), and overall survival (OS) (61% vs. 55%, P = 0.908) rates did not differ between the ONU and LNU groups. Multivariable Cox proportional regression analysis showed that surgical approach was not significantly associated with intravesical RFS (odds ratio [OR] 1.23, 95% confidence interval [CI] 0.46–3.65, P = 0.622), Overall RFS (OR 0.99, 95% CI 0.54–1.83, P = 0.974), CSS (OR 1.38, 95% CI 0.616–3.13, P = 0.444), or OS (OR 1.61, 95% CI 0.81–3.17, P = 0.17).ConclusionsThe results of this retrospective study showed no statistically significant differences in intravesical RFS, overall RFS, CSS, or OS between the laparoscopy and the open groups. Thus, LNU can be an alternative to the open procedure for T1–4/N0-X UTUC. Further studies, including a multi-institutional, prospective study are required to confirm these findings.

Diagnostic Ureteroscopy for Upper Tract Urothelial Carcinoma is Independently Associated with Intravesical Recurrence after Radical Nephroureterectomy.

ABSTRACTPurpose:To determine the effect of diagnostic ureteroscopy on intravesical recurrence in patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU).Materials and Methods:We conducted a retrospective analysis of 664 patients who were treated with RNU for UTUC from June 2000 to December 2011, excluding those who had concomitant/prior bladder tumors. Of the 664 patients, 81 underwent diagnostic ureteroscopy (URS). We analyzed the impact of diagnostic ureteroscopy on intravesical recurrence (IVR) using the Kaplan-Meier method. Univariate and multivariate analyses were used to determine the independent risk factors.Results:The median follow-up time was 48 months (interquartile range (IQR): 31-77 months). Patients who underwent ureteroscopy were more likely to have a small (p<0.01), early-staged (p=0.019), multifocality (p=0.035) and ureteral tumor (p<0.001). IVR occurred in 223 patients during follow-up within a median of 17 months (IQR: 7-33). Patients without preoperative ureteroscopy have a statistically significant better 2-year (79.3%±0.02 versus 71.4%±0.02, p<0.001) and 5-year intravesical recurrence-free survival rates (64.9%±0.05 versus 44.3%±0.06, p<0.001) than patients who underwent ureteroscopy. In multivariate analysis, the diagnostic ureteroscopy (p=0.006), multiple tumors (p=0.001), tumor size <3cm (p=0.008), low-grade (p=0.022) and pN0 stage tumor (p=0.045) were independent predictors of IVR.Conclusions:Diagnostic ureteroscopy is independently associated with intravesical recurrence after radical nephroureterectomy.

A diagnostic marker for superficial urothelial bladder carcinoma: lack of nuclear ATBF1 (ZFHX3) by immunohistochemistry suggests malignant progression.

BackgroundPathological stage and grade have limited ability to predict the outcomes of superficial urothelial bladder carcinoma at initial transurethral resection (TUR). AT-motif binding factor 1 (ATBF1) is a tumor suppressive transcription factor that is normally localized to the nucleus but has been detected in the cytoplasm in several cancers. Here, we examined the diagnostic value of the intracellular localization of ATBF1 as a marker for the identification of high risk urothelial bladder carcinoma.MethodsSeven anti-ATBF1 antibodies were generated to cover the entire ATBF1 sequence. Four human influenza hemagglutinin-derived amino acid sequence-tagged expression vectors with truncated ATBF1 cDNA were constructed to map the functional domains of nuclear localization signals (NLSs) with the consensus sequence KR[X10-12]K. A total of 117 samples from initial TUR of human bladder carcinomas were analyzed. None of the patients had received chemotherapy or radiotherapy before pathological evaluation.ResultsATBF1 nuclear localization was regulated synergistically by three NLSs on ATBF1. The cytoplasmic fragments of ATBF1 lacked NLSs. Patients were divided into two groups according to positive nuclear staining of ATBF1, and significant differences in overall survival (P = 0.021) and intravesical recurrence-free survival (P = 0.013) were detected between ATBF1+ (n = 110) and ATBF1− (n = 7) cases. Multivariate analysis revealed that ATBF1 staining was an independent prognostic factor for intravesical recurrence-free survival after adjusting for cellular grading and pathological staging (P = 0.008).ConclusionsCleavage of ATBF1 leads to the cytoplasmic localization of ATBF1 fragments and downregulates nuclear ATBF1. Alterations in the subcellular localization of ATBF1 due to fragmentation of the protein are related to the malignant character of urothelial carcinoma. Pathological evaluation using anti-ATBF1 antibodies enabled the identification of highly malignant cases that had been overlooked at initial TUR. Nuclear localization of ATBF1 indicates better prognosis of urothelial carcinoma.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2845-5) contains supplementary material, which is available to authorized users.