Intravesical Recurrence Research Articles

Developing a nomogram for predicting intravesical recurrence after radical nephroureterectomy: a retrospective cohort study of mainland Chinese patients.

To evaluate the role of Ki-67 in predicting subsequent intravesical recurrence following radical nephroureterectomy and to develop a predictive nomogram for upper tract urothelial carcinoma patients. This retrospective analysis involved 489 upper tract urothelial carcinoma patients who underwent radical nephroureterectomy with bladder cuff excision. The data set was randomly split into a training cohort of 293 patients and a validation cohort of 196 patients. Immunohistochemical analysis was used to assess the immunoreactivity of the biomarker Ki-67 in the tumor tissues. A multivariable Cox regression model was utilized to identify independent intravesical recurrence predictors after radical nephroureterectomy before constructing a nomographic model. Predictive accuracy was quantified using time-dependent receiver operating characteristic curve. Decision curve analysis was performed to evaluate the clinical benefit of models. With a median follow-up of 54months, intravesical recurrence developed in 28.2% of this sample (n=137). Tumor location, multifocality, pathological T stage, surgical approach, bladder cancer history and Ki-67 expression levels were independently associated with intravesical recurrence (all P<0.05). The full model, which intercalated Ki-67 with traditional clinicopathological parameters, outperformed both the basic model and Xylinas' model in terms of discriminative capacity (all P<0.05). Decision-making analysis suggests that the more comprehensive model can also improve patients' net benefit. This new model, which intercalates the Ki-67 biomarker with traditional clinicopathological factors, appears to be more sensitive than nomograms previously tested across mainland Chinese populations. The findings suggest that Ki-67 could be useful for determining risk-stratified surveillance protocols following radical nephroureterectomy and in generating an individualized strategy based around intravesical recurrence predictions.

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

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.

Complications and Outcomes of Salvage Cystectomy after Trimodality Therapy.

Salvage cystectomy is required for some patients with intravesical recurrence after trimodality therapy. We compared postoperative outcomes between salvage cystectomy post-trimodality therapy, primary cystectomy and primary cystectomy with prior history of nontrimodality therapy abdominal or pelvic radiotherapy. We included 265 patients who underwent radical cystectomy at Massachusetts General Hospital for cT1-T4 bladder cancer between 2003 and 2013. Patients were grouped as salvage cystectomy post-trimodality therapy, primary cystectomy or primary cystectomy with prior history of nontrimodality therapy abdominal or pelvic radiotherapy. Early (≤90 days) and late (>90 days) complications were compared. Disease-specific survival and overall survival were calculated using a Cox regression model, and adjusted survival curves were generated. The median followup from the time of cystectomy was 65.5 months. There was no difference in intraoperative and early complications between the groups. The detection of late complications was higher in salvage cystectomy post-trimodality therapy compared to primary cystectomy and primary cystectomy with prior history of nontrimodality therapy abdominal or pelvic radiotherapy (p=0.03). In multivariable Cox regression analysis, salvage cystectomy post-trimodality therapy was associated with a higher incidence of any late (HR 2.3, p=0.02) and major late complications (HR 2.1, p <0.05). There was no difference in disease-specific survival (p=0.8) or overall survival (p=0.9) between the groups. Salvage cystectomy post-trimodality therapy for intravesical recurrence post-trimodality therapy has an intraoperative and early complication rate comparable to primary cystectomy and primary cystectomy with prior history of nontrimodality therapy abdominal or pelvic radiotherapy. Salvage cystectomy post-trimodality therapy is associated with a higher risk of overall and major late complications than primary cystectomy. The disease-specific survival and overall survival of patients who require salvage cystectomy post-trimodality therapy are comparable to both groups.

Does the diagnostic modality for upper tract urothelial carcinoma prior to radical nephroureterectomy influence the risk of subsequent intravesical recurrence?

405 Background: The diagnosis of upper tract urothelial carcinoma (UTUC) is frequently obtained via diagnostic ureteroscopy (URS) with biopsy. In a recent meta-analysis of five retrospective series comparing UTUC RNU patients with and without prior diagnostic URS, prior URS was associated with intravesical recurrence of urothelial carcinoma. However, there remains an incomplete understanding of the risks of URS on intravesical recurrence after RNU, and existing studies have not examined the risks of URS without endoscopic biopsy or percutaneous biopsy alone. Here, we query our institutional RNU registry to determine if UTUC diagnostic modality influences post-RNU intravesical recurrence risk. Methods: Years 1995 to 2019 of our institutions RNU registry were queried. Patients with UTUC were divided into four groups: 1) URS with endoscopic biopsy; 2) URS without endoscopic biopsy (visual confirmation alone); 3) percutaneous biopsy without any URS; 4) no URS and no percutaneous biopsy. Exclusion criteria included pure non-urothelial histology, RNU for benign indications, and prior/concomitant cystectomy. The primary outcome was intravesical recurrence of urothelial carcinoma compared across the four groups using Kaplan-Meier log-rank analyses and Cox-proportional hazard modeling (hazard ratio = HR). Results: In a cohort of 878 patients (mean post-RNU follow-up 43 months), 461 (53%) had URS with biopsy, 130 (15%) had URS without biopsy, 229 (26%) had no URS or percutaneous biopsy, and 58 (7%) had percutaneous biopsy alone. The 3-year intravesical recurrence rate was 27%, 22%, 18%, 12% for groups 1-4, respectively. Covariates associated with intravesical recurrence on univariable analysis included age (HR 1.03, p &lt; 0.01), female gender (HR 0.76, p = 0.06), history of bladder cancer (HR 1.39, p = 0.01), current smoker (HR 1.49, p = 0.04), and multifocality (HR 1.34, p = 0.03). After adjusting for these covariates, multivariable analysis found that group 1 (URS with biopsy) was associated with increased intravesical recurrence (HR 1.41, p = 0.03) relative to group 3 (no URS or percutaneous biopsy). Compared to group 1, the hazard ratio for intravesical recurrence was not significantly different for group 2 (HR 1.18, p = 0.45) or group 4 (HR 1.11, p = 0.79). Conclusions: Patients undergoing ureteroscopic biopsy to diagnose UTUC prior to RNU had a higher risk of intravesical recurrence after RNU compared to patients who did not undergo any URS or percutaneous biopsy. This agrees with prior literature and suggests that aggressive ureteroscopic manipulation of UTUC tumors via biopsy may promote shedding of urothelial carcinoma cells capable of seeding the bladder. Our study does support the initiation of a randomized trial to determine if intravesical chemotherapy after ureteroscopic biopsy can reduce intravesical urothelial carcinoma recurrences.

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.

Fluorescent cystoscopy-assisted en bloc transurethral resection versus conventional transurethral resection in patients with non-muscle invasive bladder cancer: study protocol of a prospective, open-label, randomized control trial (the FLEBER study)

BackgroundTransurethral resection of bladder tumor (TURBT) is an essential procedure both for the treatment and staging of bladder cancer, particularly non-muscle invasive bladder cancer (NMIBC). The dissemination of cancer cells during resection and the consequent seeding into the bladder mucosa is the main cause of post-TURBT intravesical recurrence. Although the tumor dissemination is inevitable during conventional TURBT (cTURBT), this drawback can be overcome by tumor resection in one piece with intact surrounding normal tissues, referred to as en bloc resection. We previously described the photodynamic diagnosis (PDD)-assisted en bloc TURBT (EBTUR) technique and its favorable outcomes. Based on our preliminary studies, this randomized controlled trial was designed to evaluate the superiority of PDD-EBTUR to PDD-cTURBT.MethodsThe FLEBER study is a single-center randomized controlled trial in NMIBC patients who require TURBT. The longest diameter of the tumor must be between 6 and 30 mm. A total of 160 eligible patients will be enrolled after screening and randomly allocated to the PDD-EBTUR (experimental) and PDD-cTURBT (control) groups in a 1:1 ratio (80 cases to 80 cases). All patients will be treated using a single, immediate postoperative intravesical chemotherapy with epirubicin. The primary endpoint of this trial is the 2-year recurrence-free survival after surgery in pathologically proven low- or intermediate-risk NMIBC. All patients will be monitored by cystoscopy and urine cytology every 3 months for 2 years. Patient data including adverse events and complications, and data from frequency volume charts, pain scales, and health-related QOL questionnaires will be collected before and after the TURBT at indicated visits.DiscussionThe goal of this trial is to determine the potential benefits of PDD-cTURBT and PDD-EBTUR followed by a single immediate postoperative intravesical chemotherapy in patients with low- or intermediate-risk NMIBC who undergo TURBT. Ultimately, our findings will lead to the development of better interventions and potentially change the standard of care.Trial registrationThis clinical trial was prospectively registered with the UMIN Clinical Trials Registry on 1 August 2020. The reference number is UMIN000041273, and the Ethics Committee of Nara Medical University Approval ID is 2702.

Ureteroscopy for the diagnosis of upper tract urothelial cancer: The outcome in a series with 275 patients in correlation with the final histopathology

Background: There is still an unresolved debate about whether ureteroscopy (URS) and biopsy are required as a routine for the diagnosis of upper tract urothelial cancer (UTUC) or if these procedures can be omitted in appropriately selected patients. We aimed to report the overall diagnostic accuracy of URS biopsy for ureteral tumors in concordance with the final histopathology. Materials and Methods: We conducted this retrospective study from 2000 to 2019. Data on URS biopsies for ureteral tumors which included pathological diagnosis, staging, and grading were collected. These data were then compared to the results of contrast-enhanced computed tomography (CT) and the final histopathological reports. Results: The data of 275 patients with a mean age of 59 ± 11 years were collected. Complete data regarding URS biopsies for ureteral tumors were available in 94 cases with an overall diagnostic accuracy in detecting malignancy of 93%. When matched to the final histopathology, the accuracy of URS biopsies increased as the tumor grade increased. Upgrading was noticed in 36% of the biopsies. Biopsy grade was an accurate predictor of stage. CT was performed in 270 cases with an overall accuracy of 96%. URS did not affect post-UTUC intravesical recurrence (P = 0.9) or overall survival (log rank = 0.08). Conclusion: URS biopsy for ureteral tumors was highly specific with fair predictive ability for tumor grade, and it could predict tumor stage. URS may not increase intravesical recurrence or affect overall survival. However, false-negative results were noted, which did not change the surgical plan when radical surgeries were decided based on CT.

Single Short Retention Instillation of Pirarubicin Prevents Intravesical Recurrence of Low-risk Non Muscle Invasive Bladder Cancer.

This study evaluated the efficacy of a single instillation of pirarubicin with a short retention time for preventing intravesical recurrence of low-risk non-muscle-invasive bladder cancer. We analyzed 165 patients with low-risk non-muscle-invasive bladder cancer who underwent transurethral surgery. Single instillation of pirarubicin with 15-min retention time immediate after surgery was performed in 47 (28%) patients. The other patients (118, 72%) were treated without instillation therapy. The primary endpoint was recurrence-free survival. Median overall follow-up was 50 (range=6-134) months. Recurrence-free survival at 1 and 5 years was 91% and 72%, and 79% and 54% in the group treated with pirarubicin, and that treated with surgery alone, respectively (p=0.031). Cox's hazard analysis revealed lack of instillation and larger tumor size (>10 mm) as significant factors for risk of recurrence. No adverse events regarding intravesical chemotherapy were observed. Pirarubicin instillation with 15-min retention time can prevent intravesical recurrence of low-risk bladder tumors.

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.

Significance of the timing of ureteral ligation on prognosis during radical nephroureterectomy for upper urinary tract urothelial cancer.

To investigate the impact on intravesical recurrence and prognosis according to the ureteral ligation timing during radical nephroureterectomy for upper urinary tract urothelial carcinoma. We carried out a retrospective chart review of 664 patients with non-metastatic upper urinary tract urothelial carcinoma who underwent radical nephroureterectomy with ureteral ligation (supplementary analysis of JCOG1110A). We excluded patients with previous and/or synchronous bladder cancer, clinically node-positive disease, no ureteral ligation data, those without ureteral ligation and those with any missing data. We investigated the cumulative incidence of intravesical recurrence and cancer-specific mortality, and overall survival between patients with ureteral ligation before renovascular ligation (early ureteral ligation), or ureteral ligation after renovascular ligation (late ureteral ligation). Early and late ureteral ligation was carried out in 243 patients (36.6%) and 421 patients (63.4%), respectively. Intravesical recurrence occurred in 218 patients (32.8%) during follow up (median 3.9years). No significant difference in the intravesical recurrence was found between early and late ureteral ligation groups. Meanwhile, survival in the early ureteral ligation group was significantly worse compared with the late ureteral ligation group. Multivariable analysis showed that early ureteral ligation was an independent prognostic factor for overall survival (hazard ratio 1.88, 95% confidence interval 1.24-2.85, P=0.003) and cancer-specific mortality (hazard ratio 1.93, 95% confidence interval 1.14-3.25, P=0.014). Our findings suggest that the incidence of intravesical recurrence is not affected by the timing of ureteral ligation during radical nephroureterectomy. However, early ureteral ligation might have a negative impact on survival outcomes.

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

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

Postoperative Chemotherapy Bladder Instillation After Radical Nephroureterectomy: Results of a European Survey from the Young Academic Urologist Urothelial Cancer Group

BackgroundLevel 1 evidence supports the administration of single postoperative intravesical chemotherapy (pIVC) following radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), in order to decrease intravesical recurrence risk. ObjectiveThe Young Academic Urologist Urothelial Cancer Group aimed to investigate the use of pIVC in daily practice among European colleagues. Design, setting, and participantsAn online survey was shared with European Association of Urology Section of Oncological Urology (ESOU) 2017 participants via e-mail. Submissions were accepted from April to June 2017. The topics for 15 questions of this survey included the habit of delivering pIVC, the choice of drug, its dosage, related doubts or concerns, reasons not to perform pIVC, knowledge of the evidence, and surgical preferences for RNU. Outcome measurements and statistical analysisSurvey software was used for analyses. Logistic regression analyses were used to investigate the association between surgeons’ experience and caseloads with pIVC utilization. Results and limitationsOverall, 127 responses were collected (11.6%). About half of the participants (47%) regularly administered pIVC following RNU. The drug most commonly utilized was mitomycin (85%); 82% adhered to the standard dosage of 40 mg. Different administration protocols were adopted: ≤48 h (39%), 7–10 postoperative days (35%), >10 d (11%), and intraoperatively (10%). The evidence was supported by prospective randomized clinical trials for only 65% of responders. Among interviewees who did not deliver pIVC, the most commonly reported reasons were lack of supporting data (55%), fear of potential side effects (18%), and organizational hurdles (15%). ConclusionsOur research highlights the limited use of pIVC following RNU for UTUC, raising the question of how the compliance with level 1 evidence in the urological community may be promoted. Patient summaryLevel 1 evidence supports the administration of single postoperative intravesical chemotherapy (pIVC) following radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), in order to decrease intravesical recurrence risk. The Young Academic Urologist Urothelial Cancer Group aimed to investigate the use of pIVC in daily practice among European colleagues. Our research highlights the limited use of pIVC (47%) following RNU for UTUC, raising the question of how the compliance with level 1 evidence in the urological community may be promoted.

Photodynamic Diagnosis-Assisted En Bloc Transurethral Resection of Bladder Tumor for Nonmuscle Invasive Bladder Cancer: Short-Term Oncologic and Functional Outcomes.

Background: We describe the oncologic and functional outcomes and the surgical technique of the photodynamic diagnosis (PDD)-assisted en bloc transurethral resection of bladder tumor (EBTUR) using a rectangular cutting loop. Methods: We reviewed 40 patients with carcinoma in situ-free nonmuscle invasive bladder cancer undergoing PDD-TURBT. Of 40 patients, 12 underwent photodynamic diagnosis-assisted en bloc transurethral resection of bladder tumor (PDD-EBTUR) and 28 underwent PDD-assisted conventional TURBT (cTURBT). Two groups were matched in terms of clinicopathologic background and did not include patients treated with intravesical Bacillus Calmette-Guerin. The assessment of postoperative quality of life (QoL) was based on patient-reported outcome measure, including the International Prostate Symptom Score, Functional Assessment of Cancer Therapy-Bladder (FACT-BL), and 8-item Short Form (SF-8™) questionnaires before and 1 month after TUR. This study was approved by the Ethics commitee and all participants provided informed consent. Results: PDD guidance provided substantial help for circumferent demarcation around the bladder tumor, which precedes tumor dissection. One female patient (12%) treated by PDD-EBTUR had grade II bladder perforation requiring prolonged catheterization. Pathologic assessment of horizontal and vertical margins in resected specimens by PDD-EBTUR revealed that all specimens had muscularis propria, and the rate of en bloc resection was 100%. No patient had intravesical recurrence in the PDD-EBTUR group (median follow-up, 11 months), while two patients in the PDD-cTURBT group had Ta low-grade recurrent tumors (8 months). Postoperatively, scores of daytime frequency and nocturia were increased in both groups. QoL assessment using the FACT-BL and SF-8 revealed that postoperative deterioration of bladder-specific subscale and emotional/mental scores was found in the EBTUR group but not in the cTURBT group. Conclusions: Based on the initial experience on 12 patients, we considered that PDD-EBTUR is an acceptable surgical method. Further experience and research are mandatory to determine whether this technique yields better outcomes and has true clinical advantage.

IJU this issue

This issue contains 15 Original Articles, three of which are excellent prospective clinical trials, and one Urological Note. Cabozantinib is a multiple receptor tyrosine kinase inhibitor targeting MET (c-MET), VEGFR2, RET, AXL, KIT and TIE-2. In the phase III, randomized, open-label METEOR study, cabozantinib was associated with a significant progression-free survival benefit and a greater objective response rate versus everolimus in patients with metastatic renal cell carcinoma who had progressed after VEGFR-TKI. Tomita et al. (Niigata, Japan) carried out a bridging study to METEOR to evaluate the efficacy and safety of cabozantinib in Japanese patients. This phase II, open-label, single-arm study showed that cabozantinib provided clinical benefits in Japanese patients with renal cell carcinoma, with similar efficacy and safety to the non-Japanese population. Medical lasers are increasingly used to treat benign prostatic hyperplasia. Shoji et al. (Isehara, Japan) carried out a randomized prospective study to compare functional outcomes and complications over a period of 12 months in benign prostatic hyperplasia treated with thulium laser enucleation of the prostate or bipolar transurethral resection of the prostate. This study showed that thulium laser enucleation of the prostate is superior to bipolar transurethral resection of the prostate in resected volume, resected rates per prostate volume and transition zone volume, hemostasis, catheterization and hospitalization time, and decrease in prostate-specific antigen. However, excessive laser irradiation time in thulium laser enucleation of the prostate has the possibility to delay improvement of overactive bladder symptoms and decrease sexual function. Loose seeds and stranded seeds are available for low-dose rate brachytherapy. Each method has its own advantages and disadvantages, such as flexibility and fixation. Tanaka et al. (Kashihara, Japan) carried out a randomized controlled trial to compare the post-implant dosimetric parameters between the conventional method (using only the loose seeds) and the hybrid method. This study showed that the hybrid method of low-dose rate brachytherapy can achieve a higher coverage of the periprostatic region compared with the conventional method, while maintaining an acceptable level of urethral and rectal doses. The intravesical recurrence rate after transurethral resection of bladder tumor carried out for non-muscle-invasive bladder cancer (NMIBC) is high, and some risk factors for recurrence have been identified. Sazuka et al. (Chiba, Japan) evaluated the risk of the residual urine volume and preoperative pyuria in intravesical recurrence after transurethral resection of bladder tumor among NMIBC patients. They found that the presence of residual urine and pyuria raised the risk of intravesical recurrence after transurethral resection of bladder tumor for NMIBC. Furthermore, especially in men, the recurrence-free survival was significantly higher in patients without than with residual urine by propensity score matching analysis. Iwasawa et al. (Tokyo, Japan) investigated the relationship between fluid intake and tumor recurrence in NMIBC patients by using urine-specific gravity as an indicator of daily fluid intake. They found that high urine-specific gravity was associated with tumor recurrence, especially in patients not receiving adjuvant bacillus Calmette–Guérin therapy. This showed that increasing fluid intake might prevent recurrence in relatively low-risk NMIBC patients. Testicular microlithiasis (TM) is a relatively rare condition occurring in the testicular parenchyma that is characterized by multiple bright and small foci without acoustic shadow limited to the testicle on scrotal ultrasonography. TM is a characteristic of testicular dysgenesis syndrome and was shown to be associated with infertility. Hiramatsu et al. (Tokyo, Japan) evaluated the correlation between the degree of severity in TM and several factors. This study showed the prevalence of TM in normal healthy Japanese men who are trying for first-time pregnancy. This also showed that men with TM might have poor semen findings, and that men with severe TM might have even worse semen parameters. None declared.

Retrograde pyelography before radical nephroureterectomy for upper tract urothelial carcinoma is associated with intravesical tumor recurrence.

ABSTRACTPurpose: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).Materials and Methods: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.Results: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.Conclusion:Given the limitations of retrospective single-center series, performance of RGP before RNU was shown to have a negative effect on IVR after surgery.

Role of immunotherapy in Bacillus Calmette-Guérin unresponsive: non-muscle invasive bladder cancer.

Bacillus Calmette-Guérin (BCG) is recommended as the first-line treatment option for intermediate to high risk non-muscle invasive bladder cancer (NMIBC) by current clinical guidelines. However, despite the intravesical instillation of BCG, a significant proportion of patients with intermediate to high risk NMIBC develop intravesical recurrence. Moreover, the treatment of BCG-unresponsive NMIBC is currently challenging. There are no reliable treatment options for these patients with BCG-unresponsive NMIBC except radical cystectomy, which reported to show acceptable oncological outcomes. In this regards, reliable and safe non-invasive or less-invasive treatment options with acceptable oncological outcomes are awaited for the treatment of BCG-unresponsive NMIBC. The treatment of advanced or metastatic urothelial carcinoma has greatly advanced following the recent introduction of immunotherapeutic agents. These advancements have triggered an increasing interest in the use of immunotherapeutic agents for NMIBC, and especially for BCG-unresponsive NMIBC. The current review article aims to introduce and discuss the cutting-edge knowledge on the role of immunotherapy in BCG-unresponsive NMIBC and the currently available therapeutic strategies for its treatment. In addition, this article also summarizes the ongoing studies in this field.

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.

UroVysion® predicts intravesical recurrence after radical nephroureterectomy for urothelial carcinoma of the upper urinary tract: a prospective study.

Intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for urothelial carcinoma of the upper urinary tract (UCUUT) is common. One of the mechanisms driving this is the implantation of cancer cells from the UCUUT at the RNUs. Therefore, their detection after RNU can assist in predicting IVR. This study aimed to examine the utility of UroVysion® as a tool for predicting bladder recurrence after RNU for UCUUT. We prospectively enrolled 65 patients who received RNU for high-grade UCUUT between October 2013 and April 2017. Of the 65 patients, 54 (83.1%) who had both bladder urine samples available immediately after RNU (0 postoperative days: POD) and 5days after RNU (5POD) were selected. We performed UroVysion® and cytology. Twenty-two patients showed IVR with 32 foci. UroVysion® results at 0POD (26 patients, 48.1%) and/or 5POD (31 patients, 57.4%) were positive in 42 (77.8%) patients. The sensitivity, specificity, positive predictive value, and negative predictive value of UroVysion® for included cases were measured for both 0POD and 5POD samples; they were determined to be 95.5% (21/22), 34.4% (11/32), 50.0% (21/42), and 91.7% (11/12), respectively. For cytology, these values were 75.0% (15/20), 52.9% (18/34), 48.4% (15/31), and 78.3% (18/23), respectively. Forty-two (64.6%) patients who were UroVysion®-positive demonstrated IVR. The IVR rate between the group positive for either 0POD or 5POD and that negative for both significantly differed for both UroVysion® (p = 0.019) and cytology (p = 0.046). Multiple urine tests using UroVysion® after RNU could be a useful predictor for IVR.

Preoperative Monocyte-to-lymphocyte Ratio Predicts for Intravesical Recurrence in Patients With Urothelial Carcinoma of the Upper Urinary Tract After Radical Nephroureterectomy Without a History of Bladder Cancer.

This study aimed to investigate the preoperative monocyte-to-lymphocyte ratio (MLR) as a biomarker for intravesical recurrence (IVR) in upper urinary tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU) for the first time. This study involved the clinical data of 255 patients with UTUC without a history of bladder cancer who had undergone RNU from March 2004 to February 2019 at an academic institution. The associations between MLR and IVR were assessed with Kaplan-Meier method and Cox regression analysis. The median follow-up was 43.93 months. Of the 255 patients, 37 developed IVR during the follow-up period. Kaplan-Meier analysis revealed that patients with high MLR (> 0.22) had poor IVR-free survival (P= .001); this prognostic value was in accordance with patients with high grade and more advanced stage UTUC. Cox regression preoperative models showed that ureteral tumor site (hazard ratio [HR], 2.784; P= .005), surgical approach (HR, 2.745; P= .008), and high MLR (HR, 4.085; P< .001) were an independent risk factor for IVR. These factors were used as a signature to establish a prognostic risk model, which revealed significant differences among the 3 subgroups of patients with low, intermediate, and high risk (P< .001). Ureteral tumor site, surgical approach, and preoperative MLR are significant predictors for IVR in patients with UTUC after RNU. MLR may become a useful biomarker to predict IVR in patients with UTUC after RNU.