Intravesical Recurrence-free Survival Research Articles

Efficacy and toxicity of intravesical Bacillus Calmette-Guérin therapy in elderly patients with non-muscle-invasive bladder cancer.

Objectives:This study aimed to compare the efficacy and toxicity of intravesical Bacillus Calmette-Guérin (BCG) therapy between elderly and younger patients with non-muscle-invasive bladder cancer (NMIBC).Material and methods:This retrospective study included 87 NMIBC patients who received intravesical BCG between January 2011 and December 2018. We compared the treatment outcomes of patients ≥75 and <75 years old. Our primary endpoint was intravesical recurrence-free survival after treatment. The secondary endpoint was the toxicity caused by intravesical BCG.Results:The elderly and younger patients included 38 and 49 patients with mean ages of 80.6 and 66.3 years (p < 0.01), respectively. Their baseline parameters were similar, aside from age. The elderly and younger patients’ 5-year recurrence-free survival rates were 59.4% and 51.6%, respectively, and were not significantly different (log-rank test, p = 0.72). Moderate to severe pain on micturition requiring prescription medications was observed more frequently in the elderly patients than in the younger patients (p < 0.01). No elderly patients required hospitalization for any adverse events. However, 3 (6.1%) younger patients were treated for urinary tract infection in the hospital.Conclusions:The efficacy and toxicity of intravesical BCG therapy for NMIBC patients are not associated with age. Therefore, elderly patients with high-risk NMIBC should be treated in the same manner as younger patients in clinical practice.

Endoscopic management versus radical nephroureterectomy for localized upper tract urothelial carcinoma in a high endemic region

Our aim was to analyze the clinical and survival differences among patients who underwent the two main treatment modalities, endoscopic ablation and radical nephroureterectomy. This study examined all patients who had undergone endoscopic management and RNU between Jul. 1988 and Mar. 2019 from the Taiwan UTUC registry. The inclusion criteria were low stage UTUC in RNU and all cases in endoscopic managed UTUC with a curative intent. The demographic and clinical characteristics were included for analysis. In total, 84 cases in the endoscopic group and 272 cases in the RNU group were enrolled for final analysis. The median follow-up period were 33.5 and 42.0 months in endoscopic and RNU group, respectively (p = 0.082). Comparison of Kaplan–Meier estimated survival curves between groups, the endoscopic group was associated with similar overall survival (OS), cancer specific survival (CSS), and intravesical recurrence free survival (IVRS) but demonstrated inferior disease free survival (DFS) (p = 0.188 for OS, p = 0.493 for CSS and p < 0.001 for DFS). Endoscopic management of UTUC was as safe as RNU in UTUC endemic region.

Bilateral Nephroureterectomy Versus Unilateral Nephroureterectomy for Treating De Novo Upper Tract Urothelial Carcinoma After Renal Transplantation: A Comparison of Surgical and Oncological outcomes.

Background:There is currently no consensus on the optimal management of de novo unilateral upper tract urothelial carcinoma (UTUC) in renal transplant recipients. We aimed to compare the surgical and oncological outcomes of simultaneous bilateral radical nephroureterectomy (SBRNU) and unilateral radical nephroureterectomy (URNU) to determine the appropriate surgical method.Methods:Patients who developed de novo UTUC after renal transplantation and underwent surgical treatment at our center were included in the study. Outcomes were compared between the SBRNU group (underwent bilateral RNU within 3 months) and the URNU group using the Mann–Whitney U-test for continuous variables, Pearson’s chi-square test for categorical variables, and the log-rank test for survival data.Results:A total of 48 patients were identified, including 21 and 27 patients in the SBRNU and URNU groups, respectively. Comparison of perioperative data showed that the SBRNU group had a significantly longer operative time (P < .001) and hospital stay (P = .040) than the URNU group but no statistically significant difference in the blood loss (P = .171) and morbidity rate (P = .798). After a median follow-up of 65 months, the SBRNU group had a significantly longer disease-free survival (P = .009), longer cancer-specific survival (P = .032), marginally longer overall survival (P = .066), and similar intravesical recurrence-free survival (P = .274) than the URNU group.Conclusions:Our data suggest that SBRNU contributes to improved survival without significantly compromising the perioperative outcomes compared with URNU. SBRNU can be considered a feasible option for de novo UTUC after renal transplantation in specialized centers. Prospective studies should be conducted to further explore the best treatment options for this group of patients.

Effects of Complete Bladder Cuff Removal on Oncological Outcomes Following Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma.

PurposeThis study aimed to evaluate the effects of bladder cuff method on oncological outcomes in patients who underwent radical nephroureterectomy (RNU) for upper tract urothelial carcinoma.Materials and MethodsThe records of 1,095 patients treated with RNU performed at our hospital between 1994 and 2018 were retrospectively reviewed; 856 patients with no bladder tumor history were enrolled in the present study. The management of bladder cuff was divided into two categories: extravesical ligation (EL) or transvesical resection (TR). Survival was analyzed using the Kaplan-Meier method and Cox regression analyses were performed to determine which factors were associated with intravesical recurrence (IVR)–free survival (IVRFS), cancer-specific survival (CSS), and overall survival (OS).ResultsThe mean patient age was 64.8 years and the median follow-up was 37.7 months. Among the 865 patients, 477 (55.7%) underwent the TR and 379 (44.3%) the EL. Significantly higher IVRFS (p=0.001) and OS (p=0.013) were observed in the TR group. In multivariable analysis, IVR, CSS, and OS were independently associated with the EL. Among 379 patients treated with the EL, eight underwent remnant ureterectomy. Based on radical cystectomy–free survival, significant difference was not observed between the two groups. However, significantly higher IVRFS was observed in the TR group when the tumor was located in the renal pelvis.ConclusionIntramural complete excision of the distal ureter during RNU should be the gold standard approach compared with EL for the management of distal ureter in terms of oncological outcomes.

The Effect of Diagnostic Ureterorenoscopy on Intravesical Recurrence in Patients Undergoing Nephroureterectomy for Primary Upper Tract Urinary Carcinoma

Objective: The objective of this study is to evaluate the effect of diagnostic ureterorenoscopy (URS) prior to radical nephroureterectomy (RNU) on intravesical recurrence (IVR), in patients with primary upper urinary tract urothelial carcinoma (UTUC). Materials and Methods: Retrospective analysis of 354 patients, who underwent RNU for UTUC from 10 urology centers between 2005 and 2019, was performed. The primary endpoint was the occurrence of IVR after RNU. Patients were divided into URS prior to RNU (Group 1) and no URS prior to RNU (Group 2). Rates of IVR after RNU were compared, and a Cox proportional hazards model was used to evaluate potential predictors of IVR. Results: After exclusion, a total of 194 patients were analyzed: Group 1 n = 95 (49.0%) and Group 2 n = 99 (51.0%). In Group 1, a tumor biopsy and histopathological confirmation during URS were performed in 58 (61.1%). The mean follow-up was 39.17 ± 39.3 (range 12–250) months. In 54 (27.8%) patients, IVR was recorded after RNU, and the median recurrence time within the bladder was 10.0 (3–144) months. IVR rate was 38.9% in Group 1 versus 17.2% in Group 2 (p = 0.001). In Group 1, IVR rate was 43.1% in those undergoing intraoperative biopsy versus 32.4% of patients without biopsy during diagnostic URS (p =0.29). Intravesical recurrence-free survival (IRFS) was longer in Group 2 compared to Group 1 (median IRFS was 111 vs. 60 months in Groups 2 and 1, respectively (p< 0.001)). Univariate analysis revealed that IRFS was significantly associated with URS prior to RNU (HR: 2.9, 95% CI 1.65–5.41; p < 0.001). In multivariate analysis, URS prior to RNU (HR: 3.5, 95% CI 1.74–7.16; p < 0.001) was found to be an independent prognostic factor for IRFS. Conclusion: Diagnostic URS was associated with the poor IRFS following RNU for primary UTUC. The decision for a diagnostic URS with or without tumor biopsy should be reserved for cases where this information might influence further treatment decisions.

Oncological impact of different distal ureter managements during radical nephroureterectomy for primary upper urinary tract urothelial carcinoma.

BACKGROUNDThe current standard surgical treatment for non-metastatic upper urinary tract urothelial carcinoma (UTUC) is radical nephroureterectomy (RNU) with bladder cuff excision (BCE). Typically, BCE techniques are classified in one of the following three categories: An open technique described as intrasvesical incision of the bladder cuff, a transurethral incision of the bladder cuff (TUBC), and an extravesical incision of the bladder cuff (EVBC) method. Even though each of these management techniques are widely used, there is no consensus about which surgical intervention is superior, with the best oncologic outcomes.AIMTo investigate the oncological outcomes of three BCE methods during RNU for primary UTUC patients.METHODSWe retrospectively analyzed the data of 248 primary UTUC patients, who underwent RNU with BCE between January 2004 to December 2018. Patients were analyzed according to each BCE method. Data extracted included patient demographics, perioperative parameters, and oncological outcomes. Statistical analyses were performed using chi-square and log-rank tests. The Cox proportional hazards regression model was utilized to identify independent predictors. P < 0.05 was considered statistically significant.RESULTSOf the 248 participants, 39.9% (n = 99) underwent intrasvesical incision of the bladder cuff, 38.7% (n = 96) EVBC, and 21.4% (n = 53) TUBC. At a median follow-up of 44.2 mo, bladder recurrence developed in 17.2%, 12.5%, and 13.2% of the cases, respectively. Cancer-specific deaths occurred in 11.1%, 5.2%, and 7.5% of patients, respectively. Kaplan-Meier survival curves with a log-rank test highlighted no significant differences in intravesical recurrence-free survival, cancer-specific survival, and overall survival among these approaches with P values of 0.987, 0.825, and 0.497, respectively. Multivariate analysis showed that the lower ureter location appears to have inferior intravesical recurrence-free survival (P = 0.042). However, cancer-specific survival and overall survival were independently influenced by tumor stage (hazard ratio [HR] = 8.439; 95% confidence interval: 2.424-29.377; P = 0.001) and lymph node status (HR = 14.343; 95%CI: 5.176-39.745; P < 0.001).CONCLUSIONAll three techniques had comparable outcomes; although, EVBC and TUBC are minimally invasive. While based upon rather limited data, these findings will support urologists in blending experience with evidence to inform patient choices. However, larger, rigorously designed, multicenter studies with long term outcomes are still required.

The Significance of Preoperative Serum Sodium and Hemoglobin in Outcomes of Upper Tract Urothelial Carcinoma: Multi-Center Analysis Between China and the United States.

PurposeTo analyze the effect of preoperative serum sodium and hemoglobin on oncologic outcomes in upper tract urothelial carcinoma (UTUC) based on a multi-center cohort from China and the United States (U.S.).MethodsWe retrospectively reviewed the records of 775 patients with UTUC treated surgically at tertiary care medical facilities in China or the US from 1998 to 2015. We analyzed associations of preoperative serum sodium and hemoglobin with clinicopathological characteristics, overall survival (OS), cancer-specific survival (CSS) and intravesical recurrence free survival (IVRFS).ResultsThe US patients had comparatively lower serum sodium and similar hemoglobin at baseline. Preoperative low serum sodium value was associated with tumor multifocality, lymph node metastasis (LNM) and lymphovascular invasion (LVI); preoperative anemia was associated with advanced age, tumor multifocality, high tumor grade and LVI. Preoperative low serum sodium was an independent predictor of worse OS in the entire cohort; preoperative anemia was an independent predictor of worse OS and CSS in the US cohort alone, Chinese cohort alone and the combined cohort. We developed a predictive nomogram for OS which exhibited better prognostic value when it included the values of sodium and anemia, and successfully validated it in different cohorts.ConclusionPreoperative low serum sodium and anemia could be informative in predicting worse pathologic and survival outcomes in different UTUC patient ethnic groups.

Relationship between post-void residual urine volume, preoperative pyuria and intravesical recurrence after transurethral resection of bladder carcinoma.

To evaluate the relationship between residual urine volume, pyuria and bladder carcinoma recurrence. The clinical data of 305 patients who had post-void residual urine volume measured and preoperative pyuria were retrospectively collected. The patients were classified into three risk groups based on the presence of residual urine and pyuria: good (negative residual urine and pyuria), intermediate (positive residual urine or pyuria) and poor (positive residual urine and pyuria). Predictive factors for intravesical recurrence-free survival were statistically analyzed using Cox proportional hazard models and Kaplan-Meier methods. The propensity score matching method was used to adjust the patients' backgrounds. The median follow-up period for all patients was 44months. The presence of residual urine (P=0.0164) and pyuria (P=0.0233) were two independent prognostic factors for recurrence. After patients were classified into risk groups, the poor-risk group showed significantly shorter recurrence-free survival compared with that of the good- (P=0.0002) and intermediate-risk groups (P=0.0090). Even after matching, the presence of residual urine was related to short recurrence-free survival in male patients (P=0.0012). When stratified by European Organization for Research and Treatment of Cancer risk groups, the presence of pyuria was related to short recurrence-free survival, especially for intermediate-risk patients without bacillus Calmette-Guérin treatment. Post-void residual urine and preoperative pyuria are two risks for recurrence-free survival in non-muscle-invasive bladder cancer.

The Remaining Ipsilateral Ureteral Orifice Provokes Intravesical Tumor Recurrence After Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Multicenter Study With a Mid-Term Follow-Up

To investigate the impact of the remnant ureteral orifice (RUO) on the prognosis of upper tract urothelial carcinoma (UTUC), because the presence of an ipsilateral intact ureteral orifice is not an uncommon finding during follow-up cystoscopy despite the clinical relevance of bladder cuffing during radical nephroureterectomy (RNU) for the management of UTUC. The records of patients who underwent RNU in all tertiary hospitals in Daegu province (2011-2018) were retrospectively reviewed. Subjects were allocated to RUO or non-RUO groups. Cox proportional hazard models were used to identify variables. The primary endpoint was a 5-year intravesical recurrence-free survival (RFS). Of the 164 patients enrolled, 45 (27.4%) had an RUO by postoperative cystoscopy. The characteristics of the RUO and non-RUO groups were similar. During mean follow-up of 76.4 months (range: 69.5-83.4), 21 (46.7%) subjects in the RUO group and 25 (21.0%) in the non-RUO group experienced intravesical recurrence (P = .001). Among them, 3 (6.7%) and 14 (8.5%) developed distant metastasis (P = .339), and 3 (6.7%) and 9 (7.6%) succumbed to UTUC (P = .844), respectively. The 5-year RFS was lower in the RUO group than in the non-RUO counterpart (45.6% vs 77.8%, P = .003). Multivariate analysis showed lymphovascular invasion (hazard ratio [HR] = 3.593, P = .002), lymph nodal involvement (HR = 2.336, P = .038), and the presence of RUO (HR = 2.058, P = .026) predicted 5-year RFS. The presence of RUO after RNU was found to be significantly associated with intravesical tumor recurrence, and this finding emphasizes the quality of bladder cuffing during RNU, which could be assessed by complete removal of the natural orifice.

Does Xylinas' nomogram accurately predict intravesical recurrence risk after radical nephroureterectomy for primary upper urinary tract urothelial carcinoma when applied to Asian populations?

To validate a prognostic nomogram (Xylinas' nomogram) for intravesical recurrence after radical nephroureterectomy for primary upper urinary tract urothelial carcinoma patients of Asian descent. Clinicopathological and survival data from 243 primary urinary tract urothelial carcinoma patients who underwent radical nephroureterectomy with bladder cuff excision between January 2004 and May 2017 were collated. Univariate and multivariable Cox regression analyses were performed to identify independent risk factors associated with intravesical recurrence-free survival. External validation was determined using regression coefficients abstracted from previously published data. Performance was then quantified through calibration and discrimination, according to concordance indexes (c-index) in receiver operating characteristic curves. 163 patients met our eligibility criteria and were finally included in this study. At a median follow-up of 60months, intravesical recurrence occurred in 29.4% (n=48). Multivariable analysis revealed that being male, ureteral tumor location, tumor multifocality and previous bladder cancer were independent prognostic factors of intravesical recurrence-free survival. When Xylinas' nomogram was applied to our cohort, the discriminatory power was found to be roughly equivalent with a c-index of 68.3% for the reduced model and 68.4% for the full model. Calibration plots also revealed intravesical recurrence predictions at 3, 6, 12, 18, 24 and 36months had relative concordance. Contrasting the respective performances of the reduced and full model suggests there is no significant difference between the two (all P>0.05). This nomogram appears accurate at predicting intravesical recurrence after radical nephroureterectomy for primary urinary tract urothelial carcinoma in Asian populations. However, it remains necessary to data mine for unknown prognostic factors for optimization. Further external validation is required across larger, ethically diverse populations before applying this nomogram in clinical practice.

Impact of chronic kidney disease on oncological outcomes in patients with high-risk non-muscle-invasive bladder cancer who underwent adjuvant bacillus Calmette-Guérin therapy

ObjectivesTo investigate the impact of chronic kidney disease (CKD) on oncological outcomes in patients with high-risk non-muscle invasive bladder cancer (NMIBC) who underwent adjuvant induction bacillus Calmette-Guérin (BCG) therapy after transurethral resection of bladder tumor (TURBT). Materials and MethodsWe conducted a multi-institutional retrospective study assessing 209 patients with high-risk NMIBC who underwent TURBT and subsequent adjuvant induction BCG therapy from December 1998 to April 2019. Patients were divided into 2 groups: those with preoperative estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73 m2 (non-CKD group), and those with eGFR < 60 ml/min/1.73 m2 (CKD group). Primary endpoints were intravesical recurrence-free survival (RFS) and muscle-invasive bladder cancer (MIBC)-free survival. Background-adjusted multivariate analyses with the inverse probability of treatment weighting (IPTW) method using the propensity score were performed to evaluate the impact of CKD on intravesical RFS, MIBC-free survival, metastasis-free survival, cancer-specific survival, and overall survival. Moreover, multivariable analyses were performed to assess the impact of CKD on intravesical recurrence and MIBC progression, adjusting for the competing risk of death using the Fine-Gray competing risk regression model. ResultsMedian age and follow-up period after TURBT were 72 years and 45 months, respectively. Of 209 patients, 71 (34%) were diagnosed with CKD before TURBT. Background-adjusted multivariate analyses with the IPTW method indicated that CKD was significantly associated with shorter intravesical RFS, MIBC-free survival, metastasis-free survival, cancer-specific survival, and overall survival. In the Fine-Gray competing risk regression model, CKD showed significantly higher probabilities of intravesical recurrence and MIBC progression, with an adjusted subdistribution hazard ratio of 1.886 (95% confidence interval 1.069–3.330, P = 0.028) and 3.740 (95% confidence interval 1.060–13.20, P = 0.040), respectively. ConclusionsCKD presents a risk factor of poor oncological outcomes in patients with high-risk NMIBC who underwent adjuvant induction BCG therapy after TURBT.

Impact of substratification on predicting oncological outcomes in patients with primary high-risk non-muscle-invasive bladder cancer who underwent transurethral resection of bladder tumor

ObjectivesTo validate the substratification of high-risk in the European Association of Urology (EAU) guidelines and to develop the simplified substratification to improve usefulness and predictive accuracy on oncological outcomes in patients with primary high-risk nonmuscle-invasive bladder cancer (NMIBC) who underwent transurethral resection of bladder tumor (TURBT). Materials and methodsWe retrospectively evaluated 428 patients with primary high-risk NMIBC who underwent TURBT from November 1993 to April 2019. First, the efficacy of the EAU highest-risk on intravesical recurrence-free survival (RFS) and muscle-invasive bladder cancer (MIBC)-free survival was evaluated with univariate analyses. Second, we developed our simplified substratification based on multivariate analysis for intravesical RFS (lower- and higher-risk). We compared predictive accuracy on oncological outcomes using the receiver operating characteristic curve between the EAU and the simplified substratifications. ResultsMedian age and median follow-up periods were 72 years and 51 months, respectively. The EAU highest-risk was not associated with shorter intravesical RFS and MIBC-free survival (P = 0.054 and P = 0.350, respectively). In multivariate analysis, tumor size, grade 3, and chronic kidney disease were significantly associated with shorter intravesical RFS, and we developed the simplified substratification including those 3 factors. Of 428 patients, 89 (21%) were substratified into the simplified higher-risk. The predictive accuracy of the simplified substratification on intravesical recurrence, MIBC and metastasis progression, and cancer-specific mortality was significantly superior to the EAU substratification. ConclusionOur simplified substratification might contribute to improving predictive accuracy on intravesical recurrence, MIBC and metastasis progression, and cancer-specific mortality in patients with primary high-risk NMIBC who underwent TURBT.

Safety and efficacy of intensive instillation of low-dose pirarubicin vs. bacillus Calmette-Guérin in patients with high-risk non-muscle-invasive bladder cancer

ObjectivesTo evaluate the safety and efficacy of intensive intravesical instillation of low-dose pirarubicin (THP) for 6 times vs. bacillus Calmette-Guérin (BCG) without maintenance therapy after transurethral resection of bladder tumor (TURBT) in patients with primary high-risk non-muscle-invasive bladder cancer (NMIBC). Materials and MethodsWe retrospectively evaluated 370 patients with primary high-risk NMIBC who underwent TURBT from November 1993 to April 2019. The patients were divided into 2 groups: patients treated with intravesical instillation of BCG without maintenance therapy (BCG group) and intensive intravesical instillation of low-dose (20 mg) THP for 6 times within 10 days after TURBT (THP group). Safety was assessed using the Common Terminology Criteria for Adverse Events version 5.0. Background-adjusted multivariate analyses were performed to evaluate the effect of intensive intravesical instillation of low-dose THP on oncological outcomes, including intravesical recurrence-free survival (RFS), upper urinary tract RFS, muscle-invasive bladder cancer-free survival, metastasis-free survival, cancer-specific survival, and overall survival. ResultsOf the 370 patients with primary high-risk NMIBC, 180 (49%) and 190 (51%) were stratified into the BCG and THP groups, respectively. The incidence rate of adverse events of any grade in the BCG group was significantly higher than that in the THP group (P < 0.001). In the background-adjusted multivariate analyses, no significant differences were observed in oncological outcomes between the BCG and THP groups. ConclusionsIntensive intravesical instillation of low-dose THP for 6 times may be one of the treatment options in view of safety and efficacy after TURBT in patients with primary high-risk NMIBC.

MP72-07 VALIDATION AND MODIFICATION OF THE EORTC RISK TABLES TO PREDICT OUTCOMES IN NON-MUSCLE-INVASIVE BLADDER CANCER IN JAPANESE PATIENTS

You have accessJournal of UrologyBladder Cancer: Non-invasive III (MP72)1 Apr 2020MP72-07 VALIDATION AND MODIFICATION OF THE EORTC RISK TABLES TO PREDICT OUTCOMES IN NON-MUSCLE-INVASIVE BLADDER CANCER IN JAPANESE PATIENTS Hirotake Kodama*, Shingo Hatakeyama, Naoki Fujita, Hayato Yamamoto, Atsushi Imai, Takahiro Yoneyama, Yasuhiro Hashimoto, Kazuaki Yoshikawa, Atsushi Sasaki, and Chikara Ohyama Hirotake Kodama*Hirotake Kodama* More articles by this author , Shingo HatakeyamaShingo Hatakeyama More articles by this author , Naoki FujitaNaoki Fujita More articles by this author , Hayato YamamotoHayato Yamamoto More articles by this author , Atsushi ImaiAtsushi Imai More articles by this author , Takahiro YoneyamaTakahiro Yoneyama More articles by this author , Yasuhiro HashimotoYasuhiro Hashimoto More articles by this author , Kazuaki YoshikawaKazuaki Yoshikawa More articles by this author , Atsushi SasakiAtsushi Sasaki More articles by this author , and Chikara OhyamaChikara Ohyama More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000952.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To validate the stratification of the European Organization for Research and Treatment of Cancer (EORTC) risk table and to develop the simplified stratification model to improve usefulness and predictive accuracy on oncological outcomes in patients with non-muscle-invasive bladder cancer (NMIBC) who underwent transurethral resection of bladder tumor (TURBT). METHODS: We retrospectively evaluated 433 patients with primary NMIBC who underwent TURBT at from November 1993 to February 2019. We validated the usefulness of EORTC risk table on a risk classification and intravesical recurrence-free survival (RFS). we developed modified stratification based on multivariate analysis for intravesical RFS (lower- and higher-risk). We compared predictive accuracy on oncological outcomes using the receiver operating characteristic curve (ROC) and the area under the curve (AUC) between the EORTC model and the modified model. Then, we validated the modified model using 73 patients with NMIBC who underwent TURBT. RESULTS: Median age and median follow-up periods were 74 years and 29 months. Of 433 patients, 158 (36%) had recurrence after TURBT. A significant difference was observed in number of tumors (multiple) and renal function between the patients with and without recurrences. Of 433, 389 (89%) patients were classified in the high risk group. To improve the risk classification, we developed a modified risk model using number of tumors (multiple), tumor size (> 3cm), category (pT1), high grade, concurrent CIS, and the chronic kidney disease. Each factor was scored as 1 point and patients were classified into low (0-3) and high (4-6) according to total score (0-6). The AUC for recurrence prediction accuracy was significantly higher in the modified model than that in the EORTC model (0.62 vs. 0.57, P = 0.013, respectively). The recurrence free survival was significantly shorter in the patients with modified-high than that in the -low (P = 0.043). In the validation cohort, intravesical PFS was significantly shorter in the patients with the modified-high than that in the -low (P = 0.005) with the c-index of 0.76 (95% CI: 0.634-0.904). CONCLUSIONS: The modified model might be useful to classify the risk of recurrence of bladder cancer than the EORTC risk model. Further large study is necessary to validate our findings. Source of Funding: none © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1076-e1076 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hirotake Kodama* More articles by this author Shingo Hatakeyama More articles by this author Naoki Fujita More articles by this author Hayato Yamamoto More articles by this author Atsushi Imai More articles by this author Takahiro Yoneyama More articles by this author Yasuhiro Hashimoto More articles by this author Kazuaki Yoshikawa More articles by this author Atsushi Sasaki More articles by this author Chikara Ohyama More articles by this author Expand All Advertisement PDF downloadLoading ...

Preoperative chronic kidney disease predicts poor prognosis in patients with primary non–muscle-invasive bladder cancer who underwent transurethral resection of bladder tumor

ObjectivesTo evaluate the impact of preoperative chronic kidney disease (CKD) on the prognosis of patients with primary non–muscle-invasive bladder cancer (NMIBC) who underwent transurethral resection of bladder tumor (TURBT). Materials and methodsWe retrospectively evaluated 434 patients with primary NMIBC who underwent TURBT from November 1993 to April 2019. The patients were divided into 2 groups: patients with preoperative estimated glomerular filtration rate ≥60 ml/min/1.73 m2 (non-CKD group) and <60 ml/min/1.73 m2 (CKD group). Background-adjusted multivariate analyses were performed to evaluate the effect of preoperative CKD on oncological outcomes, including intravesical recurrence-free survival, muscle-invasive bladder cancer-free survival, upper urinary tract (UUT) recurrence-free survival, metastasis-free survival, cancer-specific survival, and overall survival. We evaluated predictive accuracy of CKD on prognosis using the receiver operating characteristic curve and compared between risk factors in the European Organization for Research and Treatment of Cancer scoring system and CKD plus those risk factors. ResultsThe median age and median follow-up period were 72 years and 51 months, respectively. Of 434 patients, 141 (32%) were diagnosed with CKD before TURBT. In background-adjusted multivariate analyses, CKD was an independent risk factor for those oncological outcomes, except for UUT recurrence. The predictive accuracy of CKD plus risk factors in the European Organization for Research and Treatment of Cancer scoring system on oncological outcomes was significantly improved compared with those risk factors alone, except for UUT recurrence. ConclusionPreoperative CKD was a risk factor and might improve predictive accuracy on poor prognosis in patients with primary NMIBC who underwent TURBT.

GEMINI: An open-label, single-arm, phase II trial of intraoperative gemcitabine intravesical instillation in patients undergoing radical nephroureterectomy for upper tract urothelial carcinoma.

TPS594 Background: The standard treatment for upper tract urothelial carcinoma (UTUC) is radical nephroureterectomy (RNU) with bladder cuff resection. Subsequent intravesical recurrence is common and results in patient morbidity and increased healthcare cost. Level 1 evidence has demonstrated reduction of intravesical recurrence with instillation of intravesical Mitomycin C at 10 days following RNU. However, there has been limited adoption of Mitomycin C due to concerns for toxicity and logistics of postoperative drug delivery. Meanwhile, immediate intravesical gemcitabine has been shown to reduce intravesical recurrence following transurethral resection of bladder cancers without increasing toxicity compared to placebo. Moreover, small series have suggested improved efficacy of intraoperative intravesical chemotherapy for RNU. The purpose of the GEMINI trial, therefore, is to prospectively establish the safety and efficacy of intraoperative instillation of intravesical gemcitabine in patients undergoing RNU for UTUC. Methods: GEMINI is a multi-center open-label, single-arm, Phase II study that aims to enroll 90 patients with cTa-T4N0M0 UTUC. Patients receive intraoperative intravesical instillation of gemcitabine at the beginning of RNU, to be held in the bladder for at least 1 hour. The instilled drug will be drained prior to resection of the bladder cuff. Patients will undergo standard of care postoperative surveillance, including cystoscopy at 3, 6, 12, 18, and 24 months. The primary endpoint is 1-year intravesical recurrence-free survival. The historical event rate for no treatment is 30%, and we estimated a 40% relative reduction in event rate with gemcitabine. The study is powered to provide 80% power to detect this difference based on a one-sided exact test of proportions with alpha level 0.05. Secondary endpoints include time to recurrence and stratification of recurrence free survival by tumor grade, tumor stage, neoadjuvant chemotherapy, ureteral tumor location, and history of bladder cancer. Safety and adverse event endpoints will be evaluated. Complete accrual is expected within 3 years.

Assessing the impact of different distal ureter management techniques during radical nephroureterectomy for primary upper urinary tract urothelial carcinoma on oncological outcomes: A systematic review and meta-analysis.

To assess the oncological outcomes of several distal ureter management techniques in patients administered with radical nephroureterectomy (RNU) for primary upper urinary tract urothelial carcinoma (UTUC). A systematic search of PubMed, EMBASE, and the Cochrane Library was conducted to identify studies comparing outcomes following RNU under various surgical methods for bladder cuff management. Standard cumulative analyses of hazard ratios (HRs) with 95% confidence intervals (CIs) were performed using Review Manager (5.3). Nine studies involving 4683 patients were selected based upon eligibility criteria. Meta-analysis of cancer-specific survival (CSS) and overall survival (OS) revealed no significant differences among intravesical incision of the bladder cuff (IVBC), extravesical incision of the bladder cuff (EVBC) and transurethral incision of the bladder cuff (TUBC) techniques. However, the IVBC technique appeared to have better recurrence-free survival (RFS) (HR=1.37, p<0.01) and intravesical recurrence-free survival (IRFS) (HR=1.45, p<0.01) compared with non-IVBC methods, including both TUBC and EVBC. When studies involving patients with bladder tumour history were excluded, the pooled statistic appeared to confirm that IVBC was associated with improved IRFS (HR=1.25, p=0.03) compared with EVBC and TUBC. No significant difference was found between the EVBC and TUBC groups (HR=1.81, p=0.32). The findings suggest that IVBC is associated with improved oncologic outcomes and that it may be recommended for distal ureter management. However, caution must be taken because this recommendation is based upon a very limited number of clinical studies. Further research with enhanced outcome data collection and improved reporting is required to confirm these findings.

Single-docking robotic-assisted nephroureterectomy and extravesical bladder cuff excision without intraoperative repositioning: The technique and oncological outcomes

Background/Objective: Currently there are few report of oncologic outcomes following robotic-assisted radical nephroureterectomy (RRNU) based on long-term follow-up. To evaluate the therapeutic effect of RRNU for upper tract urothelial carcinoma (UTUC), a technique of single-docking RRNU was described and its oncological outcomes was evaluated. Patients and methodsThe data of 29 patients underwent RRNU for UTUC of Ta-T3 from July 2013 to June 2016 was analyzed. The data of 131 patients of UTUC underwent laparoscopic radical nephroureterectomy (LRNU) over the same period was analyzed as control. Kaplan-Meier analysis and Cox regression were used for prognosis evaluation. ResultsThe median follow-up time was 40.5 and 40.4 months in RRNU cohort and LRNU cohort. No difference in 5-year intravesical recurrence-free survival (IVRFS) (88.0% vs. 85.5%, p = 0.611) or distant metastasis-free survival (93.1% vs.96.7%, p = 0.323) between RRNU cohort and LRNU cohort. The 5-year retroperitoneal recurrence-free survival and cancer-specific survival (CS) were lower in RRNU cohort than in LRNU cohort (77.3% vs. 87.7%, and 71.2% v.s. 84.7%, respectively). ConclusionThe single-docking RRNU is an effective treatment for UTUC, avoiding the re-docking of patient-side cart or the intraoperative reposition of patient, and bringing equivalent 5-year IVRFS compared to LRNU. However, the lower 5-year retroperitoneal recurrence-free survival and CS in RRNU cohort warned the concern of higher chance of local tumor spillage during RRNU. The noninferiority of RRNU to LRNU still needed the confirmation of large sample sized, prospective randomized controlled study.

Oncological outcomes of radical nephroureterectomy for upper urinary tract urothelial neoplasia in Denmark

Objective: To report the oncological outcomes of radical nephroureterectomy for upper urinary tract urothelial neoplasia in a large study sample.Materials and methods: This was a nationwide multicenter registry-based cohort study of all patients with upper urinary tract urothelial neoplasia in Denmark found to be eligible for nephroureterectomy between April 2004 and April 2017 (N = 1384). Primary endpoints were intravesical recurrence-free survival and overall survival. Survival probabilities were estimated with Kaplan–Meier and the log-rank test to compare survival curves. Association with clinical outcomes was studied using univariate and multivariate Cox proportional hazards.Results: Intravesical recurrence-free survival was 72% [95% confidence interval (CI) 69–75%] at 5 years and 70% (95% CI 67–73%) at 10 years. Patients with muscle-invasive disease had a significantly lower rate of intravesical recurrence [hazard ratio (HR) = 0.46, p < 0.0001] and patients with high-grade tumors had a significantly higher rate of incident intravesical recurrence compared to low-grade tumors (HR = 1.65, p = 0.001). The overall survival was 76% (95% CI 74–79%) at 5 years and 64% (95% CI 60–70%) at 10 years. Patients with higher age (p = 0.008) and muscle-invasive disease (p < 0.0001) had worse overall survival. When comparing surgical approaches, laparoscopic nephroureterectomy versus open nephroureterectomy did not differ in intravesical recurrence-free survival but was associated with shorter postoperative hospital stay (p < 0.0001) and better overall survival (p = 0.02).Conclusions: We report the oncological outcomes of radical nephroureterectomy for upper urinary tract urothelial neoplasia in a large sample and give insights into predictive factors with significant impact.

Clinical Analysis of the Predictors for Intravesical Recurrence After Laparoscopic Radical Nephroureterectomy in Japanese Patients

Objectives: In this study, we evaluate the clinicopathological independent prognostic factors which to predict IVR in patients who underwent Laparoscopic-assisted radical nephroureterectomy (LRNU) for upper urinary tract carcinoma (UTUC). Methods: Between April 2008 to February 2019, we analyzed 100 japanese patients who were underwent LRNU and 92 patients who were underwent open radical nephroureterectomy (ORNU) at our institutions by retrospectively. The Patients characteristics factors, the clinicopathologic factors were collected. The intravesical recurrence free survival (IVRFS) were analyzed using the Kaplan-Meier method and Univariate and multivariate method by using the Cox proportional hazards regression models were performed to identify independent risk factors for IVR after LRNU. Results: In LRNU group, IVR was observed in 39 cases (39%), and it was not significant difference compare with ORNU (P: 0.36). Tumor location (P=0.002), Tumor size (P=0.001), preoperative urine cytology (P<0.0001), the pneumoperitoneum time (P: 0.0005) and adjuvant chemotherapy (P=0.019) showed significant association with postoperative IVR. In the multivariate Cox hazard models, the tumor location (P=0.0003), positive preoperative urinary cytology (P=0.003), and absence of adjuvant chemotherapy (P=0.003) were independent risk factors for subsequent IVR. There were not associated with smoking, Brinkman index, hydronephrosis and ureterorenoscopy before RNU for IVR. Overal survival (OS) was not significant association for experience IVR (P=0.15). Conclusion: In this study, LRNU was not shown to have a significantly higher IVR compared to ORNU. Patients with ureteral cancer and positive preoperative urinary cytology had a higher risk of IVR after LRNU. The adjuvant chemotherapy was significantly decreased the risk for postoperative IVR.