Bladder Recurrence-free Survival Research Articles

No difference in oncological outcomes and perioperative complications between patients with ESRD with unilateral and bilateral UTUC receiving radical nephroureterectomy

Patients with end stage renal disease (ESRD) are at high risk of developing upper tract urothelial carcinoma (UTUC). Due to high recurrence rate of UTUC in contralateral kidney and ureter, and high risk of complications related to surgery and anesthesia, whether it’s necessary to remove both kineys and ureters at one time remains in debate. We utilized Taiwanese UTUC Registry Database to valuate the difference of oncological outcomes and perioperative complications between patients with ESRD with unilateral and bilateral UTUC receiving surgical resection. Patients with ESRD and UTUC were divided into three groups, unilateral UTUC, previous history of unilateral UTUC with metachronous contralateral UTUC, and concurrent bilatetral UTUC. Oncological outcomes, perioperative complications, and length of hospital stays were investiaged. We found that there is no diffence of oncological outcomes including overall survival, cancer specific survival, disease free survival and bladder recurrence free survival between these three groups. Complication rate and length of hospital stay are similar. Adverse oncological features such as advanced tumor stage, lymph node involvement, lymphovascular invasion, and positive surgical margin would negatively affect oncological outcomes.

Segmental ureterectomy outcome of upper tract urothelial carcinoma in a high endemic area: A Taiwan nationwide collaborative study

Purpose: According to the National Comprehensive Cancer Network guidelines, segmental ureterectomy (SU) of upper tract urothelial carcinoma (UTUC) is a considerable option for selected mid- and distal ureteral urothelial carcinoma (UC). As a UTUC endemic area, Taiwan lacks treatment outcome analysis of SU. Materials and methods: This study retrospectively reviewed the treatment outcomes of SU for clinically localized UTUCs. Patients with biopsy or washing cytology-confirmed UTUCs who underwent open, laparoscopic, or robot-assisted management with curative intent were retrospectively reviewed for the eligibility of analysis. Cox regression was applied for univariable and multivariable analyses. Results: A total of 161 patients who underwent SU were reviewed and analyzed. The median follow-up period was 44.5 (interquartile range, 21.6–84.9) months. After SU, 56/161 (34.8%) patients were free of UTUCs after the follow-up, 25/161 (15.5%) patients had local recurrence, and 35/161 (21.7%) had lymph node or distant metastasis. Surgical margin involvement was a risk factor associated with worse cancer-specific survival. Higher bladder recurrence and local recurrence rates were observed with concurrent bladder UC. Lymphovascular invasion and previous radical nephroureterectomy (RNU) for UC were related to higher local recurrence rates. Patients with pathological T3/T4 stage and end-stage renal disease tended to have higher metastasis rates. For the management of local recurrence, 19 patients received salvage RNU and 25 patients had adjuvant chemotherapy. However, 26/161 (16.1%) patients died of UTUCs and 2/161 (1.2%) patients died of surgery-related complications. Conclusion: SU provides acceptable oncological outcomes if the surgeons select candidates carefully. SU is not recommended if the patient has T3 or higher stage or comorbidity of end-stage renal disease. Concurrent bladder UC is a risk factor for worse bladder recurrence-free survival and local recurrence-free survival. Lymphovascular invasion and previous RNU for UC were related to higher local recurrence rates. After SU, periodic follow-up is mandatory because the local recurrence rate is higher than radical surgery.

Prognostic factors of intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinoma.

To evaluate predictive factors of increasing intravesical recurrence (IVR) rate in patients with upper tract urothelial carcinoma (UTUC) after receiving radical nephroureterectomy (RNUx) with bladder cuff excision (BCE). A total of 2114 patients were included from the updated data of the Taiwan UTUC Collaboration Group. It was divided into two groups: IVR-free and IVR after RNUx, with 1527 and 587 patients, respectively. To determine the factors affecting IVR, TNM stage, the usage of pre-operative ureteroscopy, and pathological outcomes were evaluated. The Kaplan-Meier estimator was used to estimate the rates of prognostic outcomes in overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and bladder recurrence-free survival (BRFS), and the survival curves were compared using the stratified log-rank test. Based on our research, ureter tumor, female, smoking history, age (< 70years old), multifocal tumor, history of bladder cancer were determined to increase the risk of IVR after univariate analysis. The multivariable analysis revealed that female (BRFS for male: HR 0.566, 95% CI 0.469-0.681, p < 0.001), ureter tumor (BRFS: HR 1.359, 95% CI 1.133-1.631, p = 0.001), multifocal (BRFS: HR 1.200, 95% CI 1.001-1.439, p = 0.049), history of bladder cancer (BRFS: HR 1.480, 95% CI 1.118-1.959, p = 0.006) were the prognostic factors for IVR. Patients who ever received ureterorenoscopy (URS) did not increase the risk of IVR. Patients with ureter tumor and previous bladder UC history are important factors to increase the risk of IVR after RNUx. Pre-operative URS manipulation is not associated with higher risk of IVR and diagnostic URS is feasible especially for insufficient information of image study. More frequent surveillance regimen may be needed for these patients.

Bladder-Preserving Trimodality Therapy With Capecitabine

IntroductionMany patients with muscle-invasive bladder cancer are poor candidates for radical cystectomy or trimodality therapy with maximal transurethral resection of bladder tumor (TURBT) and chemoradiotherapy with cisplatin or mitomycin C. Given the benefit of chemotherapy in bladder-preserving therapy, less-intense concurrent chemotherapy regimens are needed. This study reports on efficacy and toxicity for patients treated with trimodality therapy using single-agent concurrent capecitabine. Materials and MethodsPatients deemed ineligible for radical cystectomy or standard chemoradiotherapy by a multidisciplinary tumor board and patients who refused cystectomy were included. Following TURBT, patients received twice-daily capecitabine (goal dose 825 mg/m2) concurrent with radiotherapy to the bladder +/˗ pelvis depending on nodal staging and patient risk factors. Toxicity was evaluated prospectively in weekly on-treatment visits and follow-up visits by the treating physicians. Descriptive statistics are provided. Overall, progression-free, cancer-specific, distant metastasis-free, and bladder recurrence-free survival were estimated using the Kaplan-Meier method. ResultsTwenty-seven consecutive patients met criteria for inclusion from 2013 to 2023. The median age was 79 with 9 patients staged cT3-4a and 7 staged cN1-3. The rate of complete response in the bladder and pelvis was 93%. Overall, progression-free, cancer-specific, distant metastasis-free, and bladder recurrence-free survival at 2 years were estimated as 81%, 65%, 91%, 75%, and 92%, respectively. There were 2 bladder recurrences, both noninvasive. There were 7 grade 3 acute hematologic or metabolic events but no other grade 3+ toxicities. ConclusionMaximal TURBT followed by radiotherapy with concurrent capecitabine offers a high rate of bladder control and low rates of acute and late toxicity.

A Propensity Score–Matched Analysis of the Impact of Carcinoma In Situ on the Clinical Outcomes in Patients with Upper Tract Urothelial Carcinomas—A Nationwide Multi-Institutional Cohort Study

Purpose: This study aimed to explore the clinical prognostic features of patients treated with radical nephroureterectomy for upper tract urothelial carcinoma (UTUC) with carcinoma in situ (CIS) compared with those without it. Material and Methods: We retrospectively reviewed the data of 3285 patients with UTUC. Propensity scores were calculated using a logistic regression model to regress disease status on various baseline covariates, including cell type, tumor size, histology, lymphovascular invasion, surgical margin, and pathological stage. Using these scores, we adopted a one-to-two pair matching approach to form matched pairs between the two groups, ensuring patients within each pair had similar propensity score values. Prognostic factors were identified using univariate and multivariate Cox regression models. The Kaplan-Meier method was used to estimate the rates of prognostic outcomes, and survival curves were compared using the stratified log-rank test. Results: Matched cohorts of 810 patients without and 405 with CIS from each group were compared. There was no discernible difference in the 5-year overall survival. The Kaplan-Meier curves for cancer-specific survival were significantly different in the adjusted group only (P = .043). Multivariate Cox regression analyses indicated that disease-free and bladder recurrence-free survival rates were similar between the two groups. The CIS status was not significantly correlated with the disease-free or bladder recurrence-free survival (P = .066 and .179, respectively). Conclusions: Patients with UTUC with CIS did not exhibit significantly worse oncologic outcomes than those without it.

Perioperative and oncological outcomes of distal ureter management during nephroureterectomy for upper urinary tract urothelial carcinoma: a systematic review and meta-analysis.

The best approach of the bladder cuff (i.e., transvesical, extravesical, endoscopic) during radical nephroureterectomy (RNU) remains an unsolved question. The aim of this review is to compare the oncological and perioperative outcomes among three different approaches of the distal ureter during RNU. A literature search was conducted through June 2022 using PubMed/Medline, Embase, and Web of Science databases. Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed to identify eligible studies. The primary outcome was bladder recurrence-free survival and secondary outcomes included: perioperative outcomes, metastasis-free survival, and cancer-specific survival. A total of 19 non-randomized studies comprising 6581 patients met our inclusion criteria. The risk of bladder recurrence, metastasis and cancer-related death did not differ significantly between each approach (all P>0.05). In subgroup analysis excluding patients with history of bladder cancer, the risk of bladder recurrence remained similar between each approach (all P>0.05). There was no significant difference in terms of operative time, estimated blood loss, length of hospital stay, and postoperative complications between each approach (all P>0.05). The main limitation is the retrospective design of 18/19 included studies. The present systematic review and meta-analysis highlights the lack of high-level evidence on distal ureter management during RNU. On the basis of the available data, the present review supports the equivalence of different techniques of bladder cuff excision during RNU. The extravesical approach seems non-inferior to the transvesical approach in terms of oncological and perioperative outcomes.

High Infiltration of CD163-Positive Macrophages in Intratumor Compartment Predicts Poor Prognosis in Patients With Upper Urinary Tract Urothelial Carcinoma and Radical Nephroureterectomy.

To investigate the prognostic value of CD68- and CD163-positive macrophages in patients with upper urinary tract urothelial carcinoma (UTUC). This retrospective study enrolled 50 patients (34 men and 16 women) with UTUC who received radical nephroureterectomy (RNU). We evaluated the expression of CD68 and CD163 in the intratumor compartment by immunohistochemistry. The Kaplan-Meier method and Cox proportional hazards regression model were used to evaluate overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and bladder recurrence-free survival (BRFS). High infiltration of CD163-positive macrophages in patients with UTUC was significantly correlated with worse OS, CSS, and RFS (P < .05 for all). Multivariate analysis showed that high infiltration of CD163-positive macrophages was an independent negative prognostic factor of OS and CSS in patients with UTUC who received RNU. Lymphovascular invasion was an independent negative prognostic factor of RFS, and high infiltration of CD68-positive macrophages was an independent positive prognostic factor of BRFS. This study indicated that high infiltration of CD163-positive macrophages in the intratumor compartment might be a useful prognostic marker for survival in patients with UTUC who receive RNU. Further, high infiltration of CD68-positive macrophages in the intratumoral compartment might be a useful prognostic marker for bladder recurrence in these patients.

Surgical and oncological outcomes of robot-assisted versus laparoscopic radical nephroureterectomy for upper-tract urothelial carcinoma: A single-center comparative analysis

ABSTRACT Introduction: We retrospectively compared surgical and oncological outcomes of robot-assisted (RA) radical nephroureterectomy (RNU) in patients of upper-tract urothelial carcinoma with a cohort of patients who underwent the same procedure using a laparoscopic approach. Methods: Data of 63 consecutive patients who underwent RNU with bladder cuff excision (BCE) from 2011 to 2022 at a single tertiary care institution was retrospectively retrieved from the electronically maintained institutional database. Twenty-six cases underwent RNU with a laparoscopic approach, whereas 37 were done by RA approach. Demographic, clinical, surgical, and pathologic details and survival analyses were reported and compared. The tetrafecta of RNU, which include the performance of a BCE, lymphadenectomy, no positive surgical margin, and no major surgical complication, was also reviewed. Results: The mean age and body mass index of the robotic and laparoscopic groups were 61.5 years versus 62.7 years and 23.8 versus 24.9 kg/m2, respectively (P = 0.710 and 0.309). The Charlson Comorbidity Index and upper-tract tumor site distribution were comparable between the groups. There was no significant difference in the distribution of T stage, N stage, presence of multifocality, or lymphovascular invasion between the two groups. Although the rate of concomitant carcinoma in situ was higher in laparoscopic cohort, 42.8% versus 10.8% in robotic cohort (P = 0.004). The laparoscopic group had higher blood transfusion rates (50 vs. 13.5%, P = 0.002) and longer median hospital stays (7 vs. 4 days, P = 0.000). The median follow-up time was 21.5 versus 27 months in the laparoscopic and robotic groups. The RA group was significantly better in the achievement of the tetrafecta outcomes. The 5-year urinary bladder recurrence-free survival (UB RFS) and elsewhere RFS between the laparoscopic and robotic cohorts were 65% versus 72% and 56% versus 70%, respectively (P = 0.510 and 0.190). The laparoscopic cohort had worse 5-year cancer-specific survival and overall survival (64% vs. 90% and 58% vs. 74%, P = 0.04 and 0.08). Conclusion: The robotic approach to RNU and BCE has significantly lower transfusion rates, lower hospital stays, and significantly better cancer-specific survival rates.

Immediate gemcitabine bladder instillation following bladder closure during robotic-assisted radical nephroureterectomy: a multi-institutional report of feasibility and initial outcomes.

Bladder recurrence after radical nephroureterectomy (RNU) is common and randomized data supports utilization of prophylactic intravesical mitomycin to reduce recurrence. Recently, gemcitabine has been shown to be safe and effective at reducing recurrence following transurethral resection of bladder tumors. We sought to evaluate the safety and efficacy of a single, intraoperative gemcitabine instillation immediately following bladder cuff closure during RNU, and to compare outcomes with non-gemcitabine intravesical chemotherapy agents. We retrospectively reviewed all patients from two high volume centers who underwent robotic-assisted RNU between 2016-2020 and received either 2 g intravesical gemcitabine immediately following bladder cuff closure or non-gemcitabine intravesical chemotherapies [40 mg mitomycin C (MMC) or 50 mg doxorubicin] at the beginning of the procedure. Clinicopathologic factors were compared between cohorts. Bladder recurrence rates were evaluated using the Kaplan-Meier method and log-rank test. During RNU, 24 patients received gemcitabine and 31 patients received non-gemcitabine chemotherapy. In total, 35% (19/55) of patients experienced a bladder cancer recurrence. There was no significant difference in estimated bladder recurrence-free survival (bRFS) between gemcitabine and non-gemcitabine patient cohorts (P=0.64). By 12 months post-surgery, 25% of patients had experienced bladder recurrence. The estimated 1-year bladder RFS survival was 73% for gemcitabine and 76% for non-gemcitabine chemotherapy. Overall survival and cancer-specific survival did not differ between cohorts. No adverse events potentially attributable to the use of gemcitabine were noted within 30 days postoperatively. Gemcitabine instilled immediately following bladder cuff closure during RNU has similar bRFS rates compared to established chemotherapy agents instilled at the start of surgery.

Long-term Oncologic Outcomes of Endoscopic Management of High-risk Upper Tract Urothelial Carcinoma: The Fundació Puigvert's Experience.

Many patients with upper tract urothelial carcinoma (UTUC) outside of the low-risk criteria may possess low absolute risks of distant progression. Herein, we hypothesized that careful selection of high-risk patients undergoing an endoscopic approach could result in acceptable oncological outcomes. Patients with high-risk UTUC managed endoscopically between 2015 and 2021 were retrospectively identified from a prospectively maintained single academic institution database. Elective and imperative indications for endoscopic treatment were considered. Regarding elective indications, the decision to perform endoscopic treatment was systematically proposed to high-risk patients in whom macroscopically complete ablation was deemed feasible, excluding invasive appearance on CT-scan, and without histological variant. A total of 60 patients with high-risk UTUC met our inclusion criteria (29 imperative and 31 elective indications). The median follow-up in patients without any event was 36 months. At 5 years, the estimated overall survival, cancer-specific survival, metastasis-free survival, UTUC recurrence-free survival, radical nephroureterectomy-free survival and bladder recurrence-free survival was 57% (41-79), 75% (57-99), 86% (71-100), 56% (40-76), 81% (70-93), and 69% (54-88), respectively. All oncological outcomes were similar between patients with elective and imperative indications (all log rank p>0.05). In conclusion, we report the first large series of endoscopic treatment in patients with high-risk UTUC, arguing that promising oncologic outcomes can be achieved in properly selected candidates. We encourage multi-institutional collaborative work as a large cohort of high-risk patients treated endoscopically may allow subgroup analyses to define the best candidates.

Impact of pathological response on oncological outcomes in patients with upper tract urothelial cancer receiving neo-adjuvant chemotherapy

The purpose of this study is to evaluate the rates of pathological complete response (ypT0N0/X) and pathological response (ypT1N0/X or less) in patients with upper tract urothelial cancer who were treated with neo-adjuvant chemotherapy and to examine their impact on oncological outcomes. This study is a multi-institutional retrospective analysis of patients with high-risk upper tract urothelial cancer who underwent neoadjuvant chemotherapy and radical nephroureterectomy between 2002 and 2021. Logistic regression analyses were used to investigate all clinical parameters for response after neoadjuvant chemotherapy. Cox proportional hazard models were performed to assess the effect of the response on the oncological outcomes. A total of 84 patients with UTUC who received neo-adjuvant chemotherapy were identified. Among them, 44 (52.4%) patients received cisplatin-based chemotherapy, and 22 (26.2%) patients had a carboplatin-based regimen. The pathological complete response rate was 11.6% (n=10), and the pathological response rate was 42.9% (n=36). Multifocal tumors or tumors larger than 3cm significantly reduced the odds of pathological response. In the multivariable Cox proportional hazard model, pathological response was independently associated with better overall survival (HR 0.38, p=0.024), cancer-specific survival (HR 0.24, p=0.033), and recurrence-free survival (HR 0.17, p=0.001), but it was not associated with bladder recurrence-free survival (HR 0.84, p=0.69). Pathological response after neo-adjuvant chemotherapy and radical nephroureterectomy is strongly associated with patient survival and recurrence, and it might be a good surrogate for evaluating the efficacy of neo-adjuvant chemotherapy in the future.

Comparing Oncological and Perioperative Outcomes of Open versus Laparoscopic versus Robotic Radical Nephroureterectomy for the Treatment of Upper Tract Urothelial Carcinoma: A Multicenter, Multinational, Propensity Score-Matched Analysis

To identify correlates of survival and perioperative outcomes of upper tract urothelial carcinoma (UTUC) patients undergoing open (ORNU), laparoscopic (LRNU), and robotic (RRNU) radical nephroureterectomy (RNU). We conducted a retrospective, multicenter study that included non-metastatic UTUC patients who underwent RNU between 1990-2020. Multiple imputation by chained equations was used to impute missing data. Patients were divided into three groups based on their surgical treatment and were adjusted by 1:1:1 propensity score matching (PSM). Survival outcomes per group were estimated for recurrence-free survival (RFS), bladder recurrence-free survival (BRFS), cancer-specific survival (CSS), and overall survival (OS). Perioperative outcomes: Intraoperative blood loss, hospital length of stay (LOS), and overall (OPC) and major postoperative complications (MPCs; defined as Clavien-Dindo > 3) were assessed between groups. Of the 2434 patients included, 756 remained after PSM with 252 in each group. The three groups had similar baseline clinicopathological characteristics. The median follow-up was 32 months. Kaplan-Meier and log-rank tests demonstrated similar RFS, CSS, and OS between groups. BRFS was found to be superior with ORNU. Using multivariable regression analyses, LRNU and RRNU were independently associated with worse BRFS (HR 1.66, 95% CI 1.22-2.28, p = 0.001 and HR 1.73, 95%CI 1.22-2.47, p = 0.002, respectively). LRNU and RRNU were associated with a significantly shorter LOS (beta -1.1, 95% CI -2.2-0.02, p = 0.047 and beta -6.1, 95% CI -7.2-5.0, p < 0.001, respectively) and fewer MPCs (OR 0.5, 95% CI 0.31-0.79, p = 0.003 and OR 0.27, 95% CI 0.16-0.46, p < 0.001, respectively). In this large international cohort, we demonstrated similar RFS, CSS, and OS among ORNU, LRNU, and RRNU. However, LRNU and RRNU were associated with significantly worse BRFS, but a shorter LOS and fewer MPCs.

Replacement Instead of Discontinuation of Bacillus Calmette-Guérin Instillation in Non-Muscle-Invasive Bladder Cancer

To evaluate the efficacy of intravesical chemotherapy replacement in patients with intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC), who underwent bacillus Calmette-Guérin (BCG) instillation but discontinued due to global shortages or toxicity of BCG. This retrospective study included patients with intermediate- and high-risk NMIBC who received BCG intravesical instillation. Those who discontinued the treatment were divided into the pure BCG group and chemotherapy replacement group. Comparisons between these groups were performed. The primary endpoint was bladder recurrence-free survival (RFS). A total of 480 patients were included. Baseline characteristics were similar between groups, but the total instillation times were higher in the chemotherapy replacement group than in the pure BCG group (n = 14.9 vs. 10.5). The chemotherapy replacement group had a better three-year RFS (p = 0.022). On multivariate analysis, the pure BCG group had significantly increased all-time and 3-year recurrences (hazard ratio 2.015 and 2.148) compared to the chemotherapy replacement group. Chemotherapy replacement has a better three-year RFS than no instillation in patients with intermediate- and high-risk NMIBC who received BCG instillation but facing treatment stoppage.

A 6-month maintenance schedule of mitomycin C after radical nephroureterectomy for upper tract urothelial carcinoma for the prevention of intravesical recurrence: a retrospective, single center study.

To show the effect of a 6-month (4 times weekly followed by 5 times monthly) maintenance mitomycin C regimen on the prevention of intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). A total of 119 patients undergoing a RNU between 2007 and 2021 in a single center hospital were retrospectively reviewed. A total of 66 patients were eligible for further analysis. 27 patients received no post-operative MMC (median follow-up: 110months) and 39 patients received a 6-month (4 times weekly, 5 times monthly) maintenance regimen of MMC (median follow up: 48months). The primary outcome was the 1-, 2- and 5-year bladder recurrence free survival (BRFS). There was a significant difference (p = 0.001) in BRFS between the two groups. The 1-, 2, and 5-year BRFS for the MMC- group was 67%, 63% and 43%, respectively. The 1-, 2- and 5-year BRFS for the MMC + group was 95%, 86% and 86%, respectively. Univariate analysis showed no other potential prognostic factors that had a significant effect on the BRFS. A 6-month maintenance schedule of MMC is effective at significantly reducing the risk of IVR after RNU for UTUC. We could not find any other significant prognostic factors to predict IVR.

Oncologic impact of delay between diagnosis and radical nephroureterectomy.

This study aimed to evaluate the oncological outcome of delayed surgical wait time from the diagnosis of upper tract urothelial carcinoma (UTUC) to radical nephroureterectomy (RNU). In this multicenter retrospective study, medical records were collected between 1988 and 2021 from 18 participating Taiwanese hospitals under the Taiwan UTUC Collaboration Group. Patients were dichotomized into the early (≤90 days) and late (>90 days) surgical wait-time groups. Overall survival, disease-free survival, and bladder recurrence-free survival were calculated using the Kaplan-Meier method and multivariate Cox regression analysis. Multivariate analysis was performed using stepwise linear regression. Of the 1251 patients, 1181 (94.4%) were classifed into the early surgical wait-time group and 70 (5.6%) into the late surgical wait-time group. The median surgical wait time was 21 days, and the median follow-up was 59.5 months. Our study showed delay-time more than 90 days appeared to be associated with worse overall survival (hazard ratio [HR] 1.974, 95% confidence interval [CI] 1.166-3.343, p = 0.011), and disease-free survival (HR 1.997, 95% CI 1.137-3.507, p = 0.016). This remained as an independent prognostic factor after other confounding factors were adjusted. Age, ECOG performance status, Charlson Comorbidity Index (CCI), surgical margin, tumor location and adjuvant systemic therapy were independent prognostic factors for overall survival. Tumor location and adjuvant systemic therapy were also independent prognostic factors for disease-free survival. For patients with UTUC undergoing RNU, the surgical wait time should be minimized to less than 90 days. Prolonged delay times may be associated with poor overall and disease-free survival.

Instillation Strategies for Non-Muscle-Invasive Bladder Cancer in the Bacillus Calmette-Guerin Shortage Era: A Simple Solution for BCG Discontinuation.

Among intravesical instillation protocol in patients with non-muscle-invasive bladder cancer (NMIBC), chemotherapy agents have been widely used during the bacillus Calmette-Guérin (BCG) shortage era since the patient might under the risk of BCG discontinuation. This study evaluates the efficacy of incomplete BCG instillation compared with pure chemotherapy instillation protocol. Patients newly diagnosed with intermediate- and high-risk NMIBC who received incomplete BCG intravesical instillation or chemotherapy instillation were retrospectively included. Patients were divided into three groups according to different intravesical instillation schedules: [BCG only], [BCG + Chemo], and [Chemo only]. Comparisons between these three groups were performed. Bladder recurrence-free survival (RFS) was analyzed as the primary endpoint. A total of 475 patients who received intravesical instillations were enrolled. Compared to the [Chemo only] group, the [BCG + Chemo] group had significantly better bladder RFS (p = 0.027). Multivariate analysis of recurrence revealed the [BCG + Chemo] regimen has a hazard ratio 0.381 (95% CI 0.154-0.941, p = 0.037). The total instillation number >12 was associated with better RFS (p = 0.001) compared with other instillation numbers. For NMIBC patients facing the risk of unexpected BCG instillation interruption, instead of starting instillation with chemotherapy agents, receiving BCG first till stoppage then shifting to chemotherapy agents is recommended.

Surgical outcome predictor analysis following hand-assisted or pure laparoscopic transperitoneal nephroureterectomy using the Taiwan upper urinary tract urothelial carcinoma database.

PurposeTaiwan has a high incidence of upper tract urothelial carcinoma (UTUC). This study aimed to compare the surgical outcomes following transperitoneal hand-assisted laparoscopic nephroureterectomy (TP-HALNU) and transperitoneal pure laparoscopic nephroureterectomy (TP-LNU) from the Taiwan nationwide UTUC collaboration database using different parameters, including surgical volumes.Materials and methodsThe nationwide UTUC collaboration database includes 14 hospitals in Taiwan from the Taiwan Cancer Registry. We retrospectively reviewed the records of 622 patients who underwent laparoscopic nephroureterectomy between July 1988 and September 2020. In total, 322 patients who received TP-LNU or TP-HALNU were included in the final analysis. Clinical and pathological data and oncological outcomes were compared.ResultsOf the 322 patients, 181 and 141 received TP-LNU and TP-HALNU, respectively. There were no differences in clinical and histopathological data between the two groups. No differences were observed in perioperative and postoperative complications. There were no significant differences in oncological outcomes between the two surgical approaches. In the multivariate analysis, the cohort showed that age ≥70 years, positive pathological lymph node metastasis, tumors located in the upper ureter, and male sex were predictive factors associated with an increased risk of adverse oncological outcomes. A surgical volume of ≥20 cases showed a trend toward favorable outcomes on cancer-specific survival [hazard ratio (HR) 0.154, p = 0.052] and marginal benefit for overall survival (HR 0.326, p = 0.019) in the multivariate analysis.ConclusionAlthough different approaches to transperitoneal laparoscopic nephroureterectomy showed no significant differences in surgical outcomes, age, sex, lymph node metastasis, and tumor in the upper ureter in the following period were predictive factors for oncological outcomes. Higher surgical volume did not impact disease-free survival and bladder recurrence-free survival but was associated with improved overall survival and cancer-specific survival. Exploration of unknown influencing factors is warranted.

The Value of Preoperative Local Symptoms in Prognosis of Upper Tract Urothelial Carcinoma After Radical Nephroureterectomy: A Retrospective, Multicenter Cohort Study.

PurposeWe aimed to evaluate the impact of preoperative local symptoms on prognosis after radical nephroureterectomy in patients with upper tract urothelial carcinoma (UTUC).MethodsThis retrospective study consisted of 2,662 UTUC patients treated at 15 institutions in Taiwan from 1988 to 2019. Clinicopathological data were retrospectively collected for analysis by the Taiwan UTUC Collaboration Group. The Kaplan-Meier method was used to calculate overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and bladder recurrence-free survival (BRFS). The prognostic value of preoperative local symptoms in OS, CSS, DFS, and BRFS was investigated using Cox proportional hazards models.ResultsThe median follow-up was 36.6 months. Among 2,662 patients, 2,130 (80.0%) presented with hematuria and 398 (15.0%) had symptomatic hydronephrosis at diagnosis. Hematuria was associated with less symptomatic hydronephrosis (p <0.001), more dialysis status (p = 0.027), renal pelvic tumors (p <0.001), and early pathological tumor stage (p = 0.001). Symptomatic hydronephrosis was associated with female patients (p <0.001), less dialysis status (p = 0.001), less bladder cancer history (p <0.001), ureteral tumors (p <0.001), open surgery (p = 0.006), advanced pathological tumor stage (p <0.001), and postoperative chemotherapy (p = 0.029). Kaplan-Meier analysis showed that patients with hematuria or without symptomatic hydronephrosis had significantly higher rates of OS, CSS, and DFS (all p <0.001). Multivariate analysis confirmed that presence of hematuria was independently associated with better OS (HR 0.789, 95% CI 0.661–0.942) and CSS (HR 0.772, 95% CI 0.607–0.980), while symptomatic hydronephrosis was a significant prognostic factor for poorer OS (HR 1.387, 95% CI 1.142–1.683), CSS (HR 1.587, 95% CI 1.229–2.050), and DFS (HR 1.378, 95% CI 1.122–1.693).ConclusionsPreoperative local symptoms were significantly associated with oncological outcomes, whereas symptomatic hydronephrosis and hematuria had opposite prognostic effects. Preoperative symptoms may provide additional information on risk stratification and perioperative treatment selection for patients with UTUC.

Is Lymph Node Dissection Necessary During Radical Nephroureterectomy for Clinically Node-Negative Upper Tract Urothelial Carcinoma? A Multi-Institutional Study.

PurposeThis study aimed to compare the oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) without clinical lymph node metastasis (cN0) undergoing lymph node dissection (LND) during radical nephroureterectomy (NU).MethodsFrom the updated data of the Taiwan UTUC Collaboration Group, a total of 2726 UTUC patients were identified. We only include patients with ≥ pT2 stage and enrolled 658 patients. The Kaplan–Meier estimator and Cox proportional hazards model were used to analyze overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and bladder recurrence-free survival (BRFS) in LND (+) and LND (−) groups.ResultsA total of 658 patients were included and 463 patients without receiving LND and 195 patients receiving LND. From both univariate and multivariate survival analysis, there are no significant difference between LND (+) and LND (-) group in survival rate. In LND (+) group, 18.5% patients have pathological LN metastasis. After analyzing pN+ subgroup, it revealed worse CSS (p = 0.010) and DFS (p < 0.001) compared with pN0 patients.ConclusionsWe found no significant survival benefit related to LND in cN0 stage, ≥ pT2 stage UTUC, irrespective of the number of LNs removed, although pN+ affected cancer prognosis. However, from the result of pN (+) subgroup of LND (+) cohort analysis, it may be reasonable to not perform LND in patients with cT2N0 stage due to low positive predictive value of pN (+). In addition, performing LND may be considered for ureter cancer, which tends to cause lymphatic and hematogenous tumor spreading. Further large prospective studies are needed to validate our findings.

The Comparison of Efficacy between the Connaught and Tice Strains of Bacillus Calmette-guérin in Patients with Non-muscle-invasive Bladder Cancer in Taiwan

Purpose: The purpose of the study is to compare the efficacy of Bacillus Calmette-Guérin (BCG) strains, Connaught (ImmuCyst®), and TICE (OncoTICE®) in patients with nonmuscle invasive bladder cancer (nMIBC). Materials and Methods: Patients with nMIBC who underwent transurethral resection between March 1997 and December 2017 were enrolled. TICE was used due to the Connaught strain shortage since 2012; hence, direct comparison of the two strains could not be performed. An intravesical instillation (IVI) regimen of mitomycin-C, doxorubicin, and cisplatin (MDP) was used as the reference for comparison. The MDP group was separated into two cohorts (MDP-1 and MDP-2) that matched the same time period of Connaught and TICE treatment. Patients who did not complete the IVI course before disease recurrence or progression or were not followed up for at least 24 months were excluded. Results: A total of 730 patients were included in the analysis. There were 67 (9.2%), 38 (5.2%), and 625 (85.6%) patients who received the Connaught, TICE, and MDP treatment, respectively. During a median follow-up duration of 59 months, the recurrence rates of the Connaught, MDP-1, TICE, and MDP-2 groups were 10.5%, 22.8%, 28.9%, and 23.0%, respectively. Both BCG groups had higher tumor grades and more instances of carcinoma in situthan their corresponding MDP cohorts. The Connaught and TICE strains had similar effects in preventing tumor recurrence (Connaught vs. MDP, P= 0.876; TICE vs. MDP, P= 0.556). In the multivariable Cox proportional hazard model that included all patients, the Connaught and TICE groups had a similar risk (hazard ratio = 0.784 and 0.850) of recurrence compared to the MDP protocol. Although progression events were more frequently noticed in the Connaught group, the small number of events limited the analysis. Conclusion: The BCG strains, Connaught and TICE, had similar efficacy in reducing bladder tumor recurrence in nMIBC patients. Both strains resulted in similar bladder recurrence-free survival rates to chemotherapeutic agents.