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Intravesical Recurrence After Radical Nephroureterectomy of Upper Urinary Tract Urothelial Carcinoma: A Large Population-Based Investigation of Clinicopathologic Characteristics and Survival Outcomes.

ABSTRACT: Background: Of patients with upper urinary tract urothelial carcinoma (UTUC), 22-47% developed bladder recurrence after radical nephroureterectomy. Furthermore, the effect of surgery for UTUC-bladder cancer (BC) has not been well validated. The aim of this study was to assess the impact of standard primary BC surgical strategy on survival of patients diagnosed with UTUC-BC. Patients and Methods: A total of 676 UTUC-BC patients and 197,753 primary BC patients diagnosed from 2004 to 2016, were identified based on the SEER database. The Kaplan-Meier method and the Fine and Gray competing risks analysis were performed to assess overall survival (OS) and cancer-specific mortality (CSM). Multivariate Cox regression model and competing risks regression model were used to identify independent risk factors. Propensity score matching (PSM) was also performed to adjust potential confounding factors. Results: The baseline characteristics and survival outcomes of the two BC patient cohorts are quite different. For UTUC-BC patients, no significant difference in OS (NMIBC: p = 0.88; MIBC: p = 0.98) or cumulative incidence of CSM (NMIBC: p = 0.12; MIBC: p = 0.96) were noted for various surgical procedures. Local tumor treatment and partial cystectomy for UTUC-NMIBC patients produced lower 1-year (6.1%) and 3-year CSM (16.2%). Radical cystectomy for UTUC-MIBC patients produced lower 1-year (11.8%) but higher 3-year CSM (62.7%). After PSM for covariates, UTUC-BC patients still had a worse prognosis after surgery compared with primary BC patients. Based on regression models, older age, advanced T stage, N positive disease, M positive disease, and shorter interval between UTUC and BC were identified as independent risk factors for UTUC-BC patients. Conclusion: Standard primary BC surgical strategy did not provide significant survival benefit for UTUC-BC patients. Compared with primary BC patients, UTUC-BC patients had a worse prognosis after surgery, suggesting that current primary BC surgical guidelines are not entirely appropriate for UTUC-BC patients. Our findings underscore the continued importance and need for better prognosis and improved guidelines for management of UTUC-BC patients.

SUBMITTER: Wu J

PROVIDER: S-EPMC7938894 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Intravesical Recurrence After Radical Nephroureterectomy of Upper Urinary Tract Urothelial Carcinoma: A Large Population-Based Investigation of Clinicopathologic Characteristics and Survival Outcomes.

Wu Jie J Xu Pei-Hang PH Luo Wen-Jie WJ Dai Bo B Shen Yi-Jun YJ Ye Ding-Wei DW Wang Yu-Chen YC Zhu Yi-Ping YP

Frontiers in surgery 20210222

<b>Background:</b> Of patients with upper urinary tract urothelial carcinoma (UTUC), 22-47% developed bladder recurrence after radical nephroureterectomy. Furthermore, the effect of surgery for UTUC-bladder cancer (BC) has not been well validated. The aim of this study was to assess the impact of standard primary BC surgical strategy on survival of patients diagnosed with UTUC-BC. <b>Patients and Methods:</b> A total of 676 UTUC-BC patients and 197,753 primary BC patients diagnosed from 2004 to ...[more]

PMID: 33693025

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Project description:BackgroundNumerous studies have investigated the risk factors of intravesical recurrence (IVR) after radical nephroureterectomy (RNU) in patients with upper urinary tract urothelial carcinoma (UTUC). However, few studies explore the predictors for unfavorable pathological types of IVR following RNU.MethodsWe retrospectively reviewed 155 patients diagnosed with bladder cancer (BC) following RNU. Binary logistic regression was used for the univariable and multivariable analyses. Nomograms were developed based on the multivariable analysis. The concordance index (C-index) was used to assess the performance of the nomograms. We performed internal validation by generating calibration plots.ResultsMuscle-invasive BC (MIBC) was significantly correlated with operation interval (p = 0.004) and UTUC T-stage (p = 0.016). Operation interval (p = 0.002) and UTUC T-stage (p = 0.028) were also risk factors for BC > 3 cm. UTUC grade (p = 0.015), operation interval (p = 0.003), and hydronephrosis (p = 0.049) were independent predictors for high-grade BC (HGBC). MIBC (p = 0.018) and surgical approach (p = 0.003) were associated with multifocal IVR. Besides, MIBC and HGBC were associated with UTUC grade (p = 0.009), operation interval (p = 0.001), and hydronephrosis (p = 0.023). Moreover, only operation interval (p = 0.036) was a predictor for BC with at least one unfavorable pathological type. We developed nomograms for MIBC, HGBC, BC > 3 cm, and MIBC and/or HGBC. The calibration curves of the nomograms showed good agreement between the observation and prediction cases. The C-indexes of the nomograms were 0.820 (95% CI, 0.747-0.894), 0.728 (95% CI, 0.649-0.809), 0.770 (95% CI, 0.679-0.861), and 0.749 (95% CI, 0.671-0.827), respectively.ConclusionsThe current study found that operation interval, UTUC T-stage, UTUC grade, surgical approach, and hydronephrosis are independent predictors for unfavorable pathological types of IVR following RNU. Nomograms based on these predictors were developed and internally validated to assess the risk of developing unfavorable pathological types of IVR. Furthermore, patients at high risk of developing unfavorable pathological types BC may benefit from more active follow-up 1 year after RNU by early detection of IVR.

Project description:ObjectiveUpper urinary tract urothelial carcinoma (UUT-UC) is a very aggressive disease, characterized by 22%-50% of patients suffering from subsequent bladder recurrence after radical nephroureterectomy (RNU). Although the therapy of intravesical instillation is reported to be effective in preventing bladder recurrence, no study had been reported in Northeast China. The findings relating to the clinical effectiveness of intravesical instillation after RNU are somewhat controversial, and the best efficacy and least adverse effects of instillation drugs have not been widely accepted. Here, we aimed at evaluating the efficacy of intravesical instillation for the prevention intravesical recurrence systematically.MethodsIn this retrospective cohort study, from October 2006 to September 2017, 158 UUT-UC patients underwent RNU were divided into 4 groups: epirubicin (EPB) instillation group, hydroxycamptothecin (HCPT) instillation group, bacillus Calmette-Guerin (BCG) instillation group, and noninstillation group. Cox univariate and multivariate analyses were employed to identify the risk factors for intravesical recurrence-free survival (IVRFS). The nomogram model was also applied to predict patient outcomes. Subsequently, to evaluate the clinical significance of intravesical instillation comprehensively, several databases including PubMed, Ovid, and Embase were searched and data from published studies with our results were combined by direct meta-analysis. Moreover, a network meta-analysis comparing instillation therapies was conducted to evaluate the clinical efficacy of different instillation drugs.ResultsIn our retrospective cohort study, the Kaplan-Meier survival curve demonstrated noninstillation groups were associated with worsened IVRFS. Meanwhile, multivariate analysis indicated that intravesical instillation was independent protective factors for IVRFS (hazard ratio [HR] = 0.731). Moreover, calibration plots, receiver operating characteristic (ROC) curves, area under the curve (AUC) values, and the C-index showed the priority of nomogram's predictive accuracy. Next, direct meta-analysis including 19 studies showed that intravesical instillation could prevent the recurrence of bladder cancer with a pooled risk ratio (RR) estimate of 0.53. Subgroup analysis by study type, year of intravesical recurrence, first instillation time, and instillation times also confirmed the robustness of the results. Moreover, intraoperative instillation was associated with a decrease in the risk of bladder recurrence compared with postoperative instillation. Then, a network meta-analysis including 7 studies indicated that pirarubicin (THP) (surface under the cumulative ranking curve [SUCRA] = 89.2%) is the most effective therapy to reduce the risk of bladder recurrence, followed by BCG (SUCRA = 83.5%), mitomycin C (MMC) (SUCRA = 53.6%), EPB (SUCRA = 52.6%), and HCPT (SUCRA = 5.1%) after the analysis of the value ranking.ConclusionsA maintenance schedule of intravesical instillation prevents the recurrence of bladder cancer after RNU in UUT-UC patients effectively. Large, prospective trials are needed to further confirm its value. Compared with other chemotherapy regimens, THP may be a promising drug with favorable efficacy to prevent bladder recurrence. As included studies had moderate risk of bias, the results of network meta-analysis should be applied with caution.

Project description:Cigarette smoking is a common risk factor for developing upper tract urothelial carcinoma (UTUC).To assess the impact of cigarette smoking status, cumulative smoking exposure, and time from cessation on oncologic UTUC outcomes in patients treated with radical nephroureterectomy (RNU).A total of 864 patients underwent RNU at five institutions. The median follow-up in this retrospective study was 50 mo. Smoking history included smoking status, quantity of cigarettes per day (CPD), duration in years, and years from smoking cessation. The cumulative smoking exposure was categorized as light-short-term (? 19 CPD and ? 19.9 yr), moderate (all combinations except light-short-term and heavy-long-term), and heavy-long-term (? 20 CPD and ? 20 yr).RNU with or without lymph node dissection. No patient received neoadjuvant chemotherapy.Univariable and multivariable logistic regression and competing risk regression analyses assessed the effects of smoking on oncologic outcomes.A total of 244 patients (28.2%) never smoked; 297 (34.4%) and 323 (37.4%) were former and current smokers, respectively. Among smokers, 87 (10.1%), 331 (38.3%), and 202 (23.4%) were light-short-term, moderate, and heavy-long-term smokers, respectively. Current smoking status, smoking ? 20 CPD, ? 20 yr, and heavy-long-term smoking were associated with advanced disease (p values ? 0.004), greater likelihood of disease recurrence (p values ? 0.01), and cancer-specific mortality (p values ? 0.05) on multivariable analyses that adjusted for standard features. Patients who quit smoking ? 10 yr prior to RNU did not differ from never smokers regarding advanced tumor stages, disease recurrence, and cancer-specific mortality, but they had better oncologic outcomes then current smokers and those patients who quit smoking <10 yr prior to RNU. The study is limited by its retrospective nature.Cigarette smoking is significantly associated with advanced disease stages, disease recurrence, and cancer-specific mortality in patients treated with RNU for UTUC. Current smokers and those with a heavy and long-term smoking exposure have the highest risk for poor oncologic outcomes. Smoking cessation >10 yr prior to RNU seems to mitigate some detrimental effects. These results underscore the need for smoking cessation and prevention programs.

Dataset Information

Intravesical Recurrence After Radical Nephroureterectomy of Upper Urinary Tract Urothelial Carcinoma: A Large Population-Based Investigation of Clinicopathologic Characteristics and Survival Outcomes.

Publications

Intravesical Recurrence After Radical Nephroureterectomy of Upper Urinary Tract Urothelial Carcinoma: A Large Population-Based Investigation of Clinicopathologic Characteristics and Survival Outcomes.

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