• Upper tract urothelial carcinoma
• dialysis
• end-stage renal diseases
• intravesical recurrence
• radical nephroureterectomy

• Humans
• Female
• Male
• Retrospective Studies
• Nephroureterectomy
• Aged
• Middle Aged
• Neoplasm Recurrence, Local/epidemiology
• Renal Dialysis/adverse effects
• Carcinoma, Transitional Cell/surgery
• Carcinoma, Transitional Cell/mortality
• Carcinoma, Transitional Cell/pathology
• Urinary Bladder Neoplasms/mortality
• Urinary Bladder Neoplasms/pathology
• Urinary Bladder Neoplasms/surgery
• Prognosis
• Aged, 80 and over
• Ureteral Neoplasms/surgery
• Ureteral Neoplasms/mortality
• Ureteral Neoplasms/pathology
• Kaplan-Meier Estimate
• Proportional Hazards Models
• Neoplasm Staging

• BCG
• Bladder cancer
• Bladder tumor recurrence
• Nephroureterectomy
• Upper tract
• Urothelial carcinoma

• Aged
• Female
• Humans
• Male
• Middle Aged
• Adjuvants, Immunologic/therapeutic use
• Administration, Intravesical
• BCG Vaccine/therapeutic use
• Carcinoma, Transitional Cell/surgery
• Carcinoma, Transitional Cell/pathology
• Carcinoma, Transitional Cell/drug therapy
• Kidney Neoplasms/surgery
• Kidney Neoplasms/pathology
• Kidney Neoplasms/drug therapy
• Neoplasm Invasiveness
• Neoplasm Recurrence, Local/prevention & control
• Nephroureterectomy/methods
• Non-Muscle Invasive Bladder Neoplasms/drug therapy
• Non-Muscle Invasive Bladder Neoplasms/pathology
• Non-Muscle Invasive Bladder Neoplasms/surgery
• Retrospective Studies
• Treatment Outcome
• Ureteral Neoplasms/surgery
• Ureteral Neoplasms/pathology
• Ureteral Neoplasms/drug therapy

• adverse event (AE)
• mitomycin-C (MMC)
• radical nephroureterectomy (RNU)
• recurrence
• upper tract urothelial carcinoma (UTUC)

• diagnosis ureteroscopy
• intravesical recurrence
• nephroureterectomy
• the timing of ureteroscopy
• upper tract urothelial cancer

Upper 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.

In 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.

In 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.

A 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.

• bladder recurrence
• neutrophile-lymphocyte
• platelet-lymphocyte
• survival
• systemic immune-inflammation index
• upper tract urothelial carcinoma

• Diagnostic ureterorenoscopy
• Intravesical recurrence
• Radical nephroureterectomy
• Upper urinary tract
• Urothelial carcinoma

The 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.

To investigate the oncological outcomes of three BCE methods during RNU for primary UTUC patients.

We 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.

Of 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).

All 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.

• Bladder cuff excision
• Prognosis
• Upper urinary tract urothelial carcinoma
• Radical nephroureterectomy
• Technique
• Survival

• Intravesicular recurrence
• Nephroureterectomy
• Urine cytology
• UroVysion
• Urothelial carcinoma of the upper urinary tract

To investigate the association between preoperative retrograde pyelography (RGP), conducted to evaluate upper tract urothelial carcinoma (UTUC), and intravesical recurrence (IVR) after radical nephroureterectomy (RNU).

Of 114 patients that underwent RNU, 72 patients without preoperative ureteroscopy and a history of bladder tumor were selectively enrolled. Variables associated with IVR were identified.

RGP was performed at a mean duration of 24.9 days prior to RNU in 41 (56.1%) of study subjects. During the mean follow-up period of 64.5 months, IVRs were identified in 32 (44.4%) patients at 22.3±18.8 (mean±SD) months after RNU. Despite similar tumor characteristics in the RGP and non-RGP groups, the incidence of IVR was considerably higher in the RGP group (63.4%) than in the non-RGP group (19.4%, p <0.001). The following variables differed significantly between the IVR and non-IVR groups: age (64.6±8.51 vs. 59.6±9.65 years), tumor location (lower or upper; 53.1% vs. 20%), tumor invasiveness (> pT2; 53.1% vs. 17.5%), preoperative hemoglobin (12.8±1.36 vs. 13.9±1.65), preoperative creatinine (1.29±0.32 vs. 1.11±0.22), and preoperative RGP (81.3% vs. 37.5%), respectively. Multivariate Cox regression model showed that tumor location (p=0.020, HR=2.742), preoperative creatinine level (p=0.004, HR=6.351), and preoperative RGP (p=0.045, HR=3.134) independently predicted IVR.

Given the limitations of retrospective single-center series, performance of RGP before RNU was shown to have a negative effect on IVR after surgery.

• Nephroureterectomy
• Neoplasms
• Urography

Prophylactic intravesical chemotherapy can decrease bladder cancer recurrence rate after nephroureterectomy for upper tract urothelial carcinoma. We aimed to compare the effect of different prophylactic intravesical chemotherapy regimens in bladder recurrence-free survival. From 2000 to 2016, a total of 270 patients treated with radical nephroureterectomy at both institutions were enrolled. Patients were divided into 3 groups: multiple-instillation group, single-instillation group, and no-instillation group. Univariable and multivariable analyses with Cox regression methods were performed to calculate hazard ratios for bladder recurrence using clinicopathologic data, including our different instillation strategies. Sixty-three (23.3%) of 270 patients had subsequent intravesical recurrence. Significantly fewer patients in both the instillation groups had a recurrence compared to in the no-instillation group (13.1% vs 25.4% vs 41.5%, P = .001). Furthermore, there was a significant difference between both the instillation groups (P = .016). In different subsets of patients with upper tract urothelial carcinoma, intravesical chemotherapy, either multiple or single instillation, was a protective factor of bladder recurrence in pT2-4 (P = .002) and high grade (P < .0001). Importantly, Kaplan-Meier curves of bladder recurrence-free survival rate were increased observably in multiple-instillation group compared to that in single-instillation group (P = .053 in pT2-4 subgroup; P = .048 in high-grade subgroup, respectively). On multivariable analysis, intravesical chemotherapy (P < .001), especially multiple instillations (hazard ratio 0.230; 95% confidence interval 0.110-0.479), was identified an independent predictor of bladder recurrence-free survival. In conclusion, prophylactic intravesical chemotherapy effectively prevents bladder recurrence after nephroureterectomy, especially with multiple instillations, in patients with invasive upper tract urothelial carcinoma or at high-grade status.

• intravesical chemotherapy
• neoplasm recurrence
• nephroureterectomy
• urinary bladder
• urothelium

• Upper tract urothelial carcinoma
• cancer care
• immunotherapy
• neoadjuvant chemotherapy
• urologic advances

• bladder cancer
• intravesical chemotherapy
• meta-analysis
• nephroureterectomy
• upper tract urothelial carcinoma

• 2016R1A2B4011623 National Research Foundation of Korea (NRF) grant

Bladder recurrence after nephroureterectomy (NU) is common. However, there is no acceptable policy of adjuvant intravesical treatment after NU.

To assess the rate of bladder recurrence following NU and to identify the high-risk subgroups that may become candidates for adjuvant intravesical therapy after NU.

Ninety-one patients (mean age 66.4 years) underwent NU. High-grade (HG) tumors were found in 63 patients and low-grade (LG) tumors in 28. Median follow-up was 72 months. The risk of bladder recurrence was assessed by uni- and multivariate analyses of patient and tumor characteristics.

Bladder recurrence developed in 38 patients (41.8%) after a median period of 11 months. Among these, 25 patients with HG upper tract urothelial carcinoma (39.7%) and 13 patients with LG upper tract urothelial carcinoma (46.4%) developed recurrence. HG bladder recurrence developed in 24 patients (63.2%) and LG recurrence developed in 14 patients (36.8%). Stages pTa, pT1, pT2, or higher bladder recurrence developed in 26 (68.4%), 7 (18.4%), and 4 patients (10.5%), respectively, and pure pTis developed in 1 patient. On uni- and multivariate analyses, the risk of bladder recurrence was independent of any clinicopathologic characteristics.

High rate and short time interval of bladder recurrence after NU were found, with no specific subgroup of patients with increased risk. These findings support prescribing adjuvant intravesical therapy to all patients after NU.

• bladder recurrence
• nephroureterectomy
• urothelial upper tract tumors

• BCG
• Upper tract
• instillations
• intracavitary therapy
• urothelial carcinoma

• Bladder tumour relapse.
• Factores pronósticos
• Prognostic factors
• Recidiva vesical
• Tumor de urotelio superior
• Upper urothelium tumour

• Adult
• Aged
• Aged, 80 and over
• Carcinoma, Transitional Cell/epidemiology
• Carcinoma, Transitional Cell/surgery
• Female
• Humans
• Kidney Neoplasms/epidemiology
• Kidney Neoplasms/surgery
• Male
• Middle Aged
• Neoplasm Recurrence, Local/epidemiology
• Neoplasms, Second Primary/epidemiology
• Prognosis
• Retrospective Studies
• Ureteral Neoplasms/epidemiology
• Ureteral Neoplasms/surgery
• Urinary Bladder Neoplasms/epidemiology
• Urothelium

• network meta-analysis
• perioperative treatment
• upper tract urothelial carcinoma

• Bayes Theorem
• Combined Modality Therapy
• Disease Management
• Humans
• Perioperative Care/methods
• Survival Analysis
• Treatment Outcome
• Urethral Neoplasms/mortality
• Urethral Neoplasms/pathology
• Urethral Neoplasms/therapy
• Urologic Neoplasms/mortality
• Urologic Neoplasms/pathology
• Urologic Neoplasms/therapy

• Carcinoma, Transitional Cell/epidemiology
• Carcinoma, Transitional Cell/surgery
• Female
• Humans
• Male
• Neoplasm Recurrence, Local/epidemiology
• Ureter/surgery
• Urinary Bladder Neoplasms/epidemiology
• Urinary Bladder Neoplasms/surgery

Diagnostic ureterorenoscopy is powerful tool to confirm upper tract urothelial cancer (UTUC). However, URS and associated manipulation may be related to the risk of intravesical recurrence (IVR) following radical nephroureterectomy (RNU). We aimed to investigate whether preoperative ureterorenoscopy would increase IVR after RNU in patients with UTUC. We performed a retrospective analysis of 630 patients who had RNU with bladder cuff excision due to UTUC. Diagnostic URS was performed in 282 patients (44.7%). Patients were divided into two groups according to the URS. Survival analysis and multivariate Cox regression model were performed to address risk factors for the IVR. The interval from URS to RNU was measured. During URS, manipulation such as biopsy and resection was determined. The median age was 64 (IQR 56–72) years with follow-up duration of 34.3 (15.7–64.9) months. Median time from URS to RNU was 16 (0–38) days. The IVR developed in 42.5% (n = 268) patients at 8.2 (4.9–14.7) months. The five-year IVR-free survival rate was 42.6 ± 8.0% and 63.6 ± 6.9% in patients with and without preoperative URS, respectively (P < 0.001). In multivariate analysis, previous history of bladder tumour, extravesical excision of distal ureter, multifocal tumour, and URS (HR, 95% CI; 1.558, 1.204–2.016, P = 0.001) were independent predictors for higher IVR. The IVR rate in patients without manipulation during URS was not different to those with manipulation (P = 0.658). The duration from URS to RNU was not associated with IVR (P = 0.799). Diagnostic URS for UTUC increased IVR rate after RNU. However, the lessening of interval from URS to radical surgery or URS without any manipulation could not reduce the IVR rate.

• Aged
• Carcinoma, Transitional Cell/diagnosis
• Carcinoma, Transitional Cell/pathology
• Carcinoma, Transitional Cell/secondary
• Carcinoma, Transitional Cell/surgery
• Disease-Free Survival
• Female
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Neoplasm Recurrence, Local/etiology
• Neoplasm Seeding
• Nephrectomy/methods
• Preoperative Care
• Proportional Hazards Models
• Retrospective Studies
• Risk Factors
• Ureter/pathology
• Ureter/surgery
• Ureteral Neoplasms/pathology
• Ureteral Neoplasms/surgery
• Ureteroscopy/adverse effects
• Urinary Bladder Neoplasms/diagnosis
• Urinary Bladder Neoplasms/secondary
• Urinary Bladder Neoplasms/surgery

• Inflammation
• Recurrence
• Risk factors
• Transitional cell carcinoma

• bladder recurrence
• endoscopic bladder cuff excision
• extravesical bladder cuff excision
• nephroureterectomy
• oncological outcome

Upper urinary tract urothelial carcinoma (UTUC) is a rare disease, and novel prognostic factors for patients who have undergone a radical nephroureterectomy (RNU) for UTUC have been studied intensely. To the best of our knowledge, the prognostic value of urothelial recurrence in patients with UTUC has not been previously described in studies. The present study compared the prognostic value of urothelial and non-urothelial recurrence in patients with UTUC of the kidney and ureter managed by surgery. The inclusion criteria consisted of a diagnosis of non-metastatic UTUC (any T stage, N0–1 and M0) and receipt of an RNU with an ipsilateral bladder cuff as the primary treatment. Of the 153 patients that were screened for the study, comprehensive clinical and pathological data was available for 103 patients, who were consequently included in the analysis. Overall survival (OS) and cancer-specific survival (CSS) times were estimated. A multivariate analysis was performed using the Cox regression model. The median follow-up period was 29 months (interquartile range, 14–63 months). The patient population was comprised of 71 males (68.9%) and 32 females (31.1%). A total of 32 patients (31.1%) showed non-urothelial recurrence, while 38 patients (36.9%) exhibited urothelial recurrence and 33 patients (32.0%) exhibited no recurrence. When comparing the risk parameters between the non-urothelial recurrence categories, the factors of pathological grade, microvascular invasion, lymphatic invasion and pT classification showed significant differences. However, there were no significant differences between the urothelial recurrence categories. No significant difference was observed between the OS and CSS times within the urothelial recurrence categories (P=0.3955 and P=0.05891, respectively), but significant differences were identified in the non-urothelial recurrence categories (P<0.0001 and P<0.0001, respectively). Among the other relevant descriptive pre-operative characteristics in the multivariate analysis, only non-urothelial recurrence remained associated with a worse CSS [P=0.002; hazard ratio (HR) 9.512]. The results show that urothelial recurrence has a minimal prognostic value in patients with UTUC managed by RNU with an ipsilateral bladder cuff.

• non-urothelial recurrence
• prognosis
• upper urinary tract urothelial carcinoma

• endoscopic
• laparoscopic
• nephroureterectomy
• renal pelvis
• upper tract urothelial carcinoma
• ureter