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BACKGROUND: The benefit of surgery of the primary tumor in metastatic bladder cancer is unknown. OBJECTIVE: Perform a comprehensive contemporary literature review on the benefit of surgery of the primary tumor in metastatic bladder cancer. METHODS: Ovid MEDLINE, Ovid EMBASE, and Cochrane Library from January 1, 1990 to April 20, 2020 were queried for relevant articles published in English. Each article was evaluated by at least two content experts prior to inclusion which were blinded to the other’s evaluation. A third content expert was used when there was not a unanimous decision. Additional articles were added at the discretion of the authors. RESULTS: Long-term survival is possible in patients with initially unresectable and/or limited metastatic disease. Multi-modal therapy with chemotherapy and surgery have the most favorable outcomes when compared to single treatment modalities in selected populations. Patients who demonstrate a robust response to pre-surgical therapy are likely to benefit the most from consolidative surgery. Patients with distant metastatic disease may benefit from consolidative surgery; however, this benefit may only be seen in those with metastatic disease limited to one site. CONCLUSIONS: Surgery of the primary tumor in metastatic bladder cancer either in the setting of surgery alone, consolidative therapy or coupled with adjuvant therapy may be beneficial in well selected patients and should generally be limited to those who have a response to primary chemotherapy. Randomized clinical control trials are needed to further our understanding of the role of surgery in metastatic bladder cancer.

Background Guideline indications for restaging transurethral resection (reTUR) for high-grade (HG) Ta bladder tumors vary due to a paucity of data. Objective To investigate guideline-based, risk-adapted approaches to reTUR for HG Ta lesions. Design, setting, and participants An institutional review of HG Ta patients who received adequate bacillus Calmette-Guerin (BCG) from 2000 to 2019 was conducted. Outcome measurements and statistical analysis Guideline criteria for reTUR were used to stratify patients. Kaplan-Meier product limits estimated survival. Cox regression and log-rank tests identified association of variables with survival. Results and limitations Of the 209 patients with HG Ta bladder cancer, 104 (50%) underwent reTUR, which identified residual disease in 39 patients (38%). Only one patient (1%) was upstaged to pT1 on reTUR. In all unstratified HG Ta patients, reTUR was associated with improved progression-free survival (p = 0.050) and recurrence-free survival (RFS; p = 0.003). The 5-yr RFS for patients who underwent versus those who did not undergo reTUR based on AUA guidelines was 73% (95% confidence interval 63–81%) versus 52% (40–62%), and for those who underwent versus those who did not undergo reTUR based on EAU guidelines was 76% (61–86%) versus 22% (4–49%). In 45 patients meeting both AUA high-risk criteria (large, multifocal tumors) and EAU criteria (lack of detrusor muscle) for reTUR, lack of restaging was associated with over a two-fold increase in recurrence (67% vs 15%, p = 0.002) and progression (25% vs 6%, p = 0.109). Data were limited by selection bias unaccounted for in selecting candidates for reTUR. Conclusions Restaging TUR in all HG Ta patients, regardless of risk stratification, was associated with improved outcomes. The benefit of reTUR was most notable in high-risk patients without muscle in the index specimen, consistent with components of both AUA and EAU guidelines. These data support a non–risk-adapted approach to reTUR for all HG Ta lesions. Patient summary Restaging bladder tumor resection improves outcomes in patients with high-grade Ta tumors treated with bacillus Calmette-Guerin (BCG).

This is a longitudinal prospective study that tracked multiple symptom burden and functioning status for bladder cancer (BLC) patients for 3 months post-radical cystectomy at The University of Texas MD Anderson Cancer Center, using a validated disease-specific patient-reported outcome measure (PROM) tool, the MD Anderson Symptom Inventory (the MDASI-PeriOp-BLC). The feasibility of collecting an objective measure for physical functioning, using “Timed Up & Go test” (TUGT) and PRO scores at baseline, discharge and end of study, was tested. Patients (n = 52) received care under an ERAS pathway. The more severe scores of fatigue, sleep disturbance, distress, drowsiness, frequent urination and urinary urgency at baseline predicted poor functional recovery postoperatively (OR = 1.661, 1.039–2.655, p = 0.034); other more severe symptoms at discharge (pain, fatigue, sleep disturbance, lack of appetite, drowsiness, bloating/abdominal tightness) predicted poor functional recovery (OR = 1.697, 1.114–2.584, p = 0.014) postoperatively. Compliance rates at preoperative, discharge and end of study were 100%, 79% and 77%, while TUGT completion rates were 88%, 54% and 13%, respectively. This prospective study found that more severe symptom burden at baseline and discharge is associated with poor functional recovery post-radical cystectomy for BLC. The collection of PROs is more feasible than using performance measures (TUGT) of function following radical cystectomy.

Supplemental Figure 1. Gene set enrichment analysis. Supplemental Figure 2. TCF21 expression analysis. Supplemental Figure 3. TCF21 expression in cell lines. Supplemental Figure 4. Loss-of-function and gain-of-function studies of TCF21 Supplemental Figure 5. CD24 and CD44 expression in TCF21 OE UM-UC3 and UM-UC13 cells. Supplemental Figure 6. GSEA analysis of common pathways altered between the three cell lines. Supplemental Figure 7. Heatmap of hierarchical clustering of luminal markers showing differential expression after TCF21 upregulation in UC13 LN (A) and UC13 MET (B) cells.

The 2021 European Association of Urology (EAU) guidelines contain updated prognostic factor risk groups for non-muscle-invasive bladder cancer (NMIBC). These groups are based on the following predictors of progression: tumour stage, grade, number, and size; concomitant carcinoma in situ; and age. However, the groups were derived from datasets excluding patients treated with bacillus Calmette-Guérin (BCG).To determine the validity of the updated EAU prognostic factor risk groups in patients with NMIBC treated with BCG.We reviewed patients treated with BCG at our institution between 2000 and 2018. Patients were analysed according to the receipt of "at least induction" and "adequate" BCG (as defined by the US Food and Drug Administration). Risk groups were assigned according to the 2021 EAU NMIBC risk calculator (https://nmibc.net/).The Kaplan-Meier method was used to estimate the risks of progression at 1 and 5 yr. Probabilities of progression obtained with the updated prognostic factor risk groups in our series were compared with those reported by the EAU. Discrimination was assessed using the concordance index (c-index).A total of 529 patients received at least induction BCG with a median follow-up of 47.3 mo (interquartile range 25.3-86.9). Of these patients, 494 received adequate BCG. We found lower progression rates at 1 yr in the very-high-risk group patients receiving at least induction (6.9%) and adequate BCG (4.0%) versus 16.0% for the EAU predicted rates. Additionally, progression rates were also lower at 5 yr in the high-risk group-7.4% for at least induction and 5.3% for adequate BCG versus 9.6% for EAU predicted rates; the rates in the very-high-risk group were as follows: 16.7% for at least induction and 14.9% for adequate BCG versus 40.0% for EAU predicted rates. The c-index in our series was lower than that reported by the EAU (0.63 vs 0.80). Of interest, our multivariable analysis identified grade, stage, and age (p0.02) to be the predictors of progression after BCG therapy.While the 2021 EAU prognostic factor risk groups successfully stratified progression risks in our cohort, treatment with BCG reduced their discriminative ability. Furthermore, the groups overestimate progression risks in BCG-treated patients. These findings should be used in conjunction with the updated risk groups to counsel patients with higher-risk NMIBC about their risk of progression with and without BCG.Although the updated European Association of Urology prognostic factor risk groups are able to stratify patients with non-muscle-invasive bladder cancer according to their risk of progression to muscle-invasive bladder cancer, this risk is overestimated in patients treated with bacillus Calmette-Guérin (BCG).

Purpose:Data from the pre-neoadjuvant chemotherapy (NAC) era suggests patients who progress on bacillus Calmette-Guerin (BCG) to muscle-invasive bladder cancer (P-MIBC) exhibit worse outcomes compa...

We sought to evaluate the impact of repeat transurethral resection of bladder tumor prior to radical cystectomy on oncologic outcomes in a contemporary cohort at a tertiary care center.An Institutional Review Board approved review of 657 patients diagnosed with muscle-invasive bladder cancer who underwent radical cystectomy at our institution for clinical stage T2 urothelial carcinoma between 2005 and 2017 was performed. Patients with and without repeat transurethral resection of bladder tumor were matched 1-to-1 by propensity score. Matching was done by age, gender, receipt of neoadjuvant chemotherapy, preoperative hydronephrosis, variant histology, lymphovascular invasion, or carcinoma in situ on index transurethral resection of bladder tumor.A total of 548 patients with muscle-invasive bladder cancer were included after matching (2 groups of 274 patients). Kaplan-Meier estimates of recurrence-free and overall survival demonstrated no significant difference based upon performance of repeat transurethral resection of bladder tumor (Repeat transurethral resection of bladder tumor prior to radical cystectomy, irrespective of receipt of neoadjuvant chemotherapy, was not associated with improved survival outcomes in this propensity score matched muscle-invasive bladder cancer cohort. The absence of residual tumor on pathological evaluation of repeat transurethral resection of bladder tumor specimen was prognostic and was associated with improved survival outcomes. However, a large percentage of patients with pT0 disease on repeat transurethral resection of bladder tumor had residual disease on radical cystectomy pathology.

According to the American Urological Association/American Society of Clinical Oncology/American Society for Radiation Oncology/Society of Urologic Oncology Guideline on treatment of nonmetastatic muscle invasive bladder cancer (MIBC), females requiring radical cystectomy (RC) should undergo concomitant anterior pelvic exenteration despite low rates of malignant involvement of gynecologic organs. We present the clinicopathological characteristics of patients with MIBC treated with neoadjuvant chemotherapy (NAC) and evaluate the impact of NAC on gynecologic organ involvement.An institutional review board approved review of patients with cT2-T3 MIBC treated with RC at our institution between 2005 and 2018 was performed. Patients were stratified by receipt of NAC.A total of 186 females with cT2-T3 MIBC underwent RC during the study period, of whom 67.7% received NAC prior to RC. Patients who received NAC were more likely to have cT3 disease, preoperative hydronephrosis, and variant histology on transurethral resection (p0.001, p=0.004, p=0.029, respectively). Rates of recurrence or metastasis were similar between groups (27.0% vs 26.7%, p=0.964). No patients had isolated genitourinary organ recurrence (median followup 32.1 months). Nine patients (5.7%) had gynecologic organ involvement (6 NAC vs 3 no NAC, p=0.978). Among those who underwent hysterectomy, 2 patients (3.1%) who received NAC had uterine involvement compared to none in the no NAC cohort (p=0.551). Rates of vaginal involvement were similar between the groups (4 NAC vs 3 no NAC, p=0.402). Additionally, 1 patient who received NAC had incidentally diagnosed localized endometrial cancer. No women had fallopian tube or ovarian involvement.Even among high risk patients with MIBC, gynecologic organ involvement of MIBC is rare, and organ preservation, especially of the ovaries, is likely safe.

Purpose: Our objective was to establish the incidence of positive surgical margins, recurrence patterns, and recurrence-free (RFS) and overall survival (OS) in a large cohort of patients undergoing...

BACKGROUND: The optimal management of non-invasive (mucosal and/or ductal) urothelial carcinoma of the prostate remains elusive and there is a paucity of data to guide treatment. OBJECTIVE: Our objective was to systematically review and synthesize treatment responses to conservative management of non-invasive prostatic urothelial carcinoma using intravesical therapy. METHODS: A systematic literature search using MEDLINE, EMBASE, Cochrane Library, SCOPUS, and Web of Science databases from inception to November 2019 was performed. Risk of bias assessment was performed using the Newcastle-Ottawa scale for non-randomised studies. Pooled estimates of complete response in the bladder and prostate and prostate only were performed using a random effects model. Pre-specified subgroup analyses were generated to assess differences in complete responses for: BCG therapy vs other agents, ductal vs mucosal involvement, CIS vs papillary tumors and TURP vs no TURP. RESULTS: Nine studies including 175 patients were identified for inclusion in the systematic review and meta-analysis. All were retrospective case series and most evaluated response to BCG therapy. The pooled global complete response rate for intravesical therapy was 60%(95%CI: 0.48, 0.72), and for prostate 88%(95%CI: 0.81, 0.96). Pre-specified analyses did not demonstrate statistically significant differences between subgroups of interest. CONCLUSIONS: Management of non-invasive prostatic urothelial carcinoma using intravesical therapy yields satisfactory results. Caution should be taken in treating patients with papillary tumors and ductal involvement, as data for these populations is limited. TURP may not improve efficacy, but is required for staging. Current recommendations are based on low quality evidence, and further research is warranted.

Objectives: We developed and validated a disease-specific tool for perioperative patient-reported outcomes assessment for bladder cancer (BLC) patients undergoing radical cystectomy, The MD Anderson Symptom Inventory (the MDASI-PeriOp-BLC). Methods: Patients who underwent radical cystectomy were recruited. We used qualitative interviews and experts’ input to generate disease/treatment-specific items of the MDASI-PeriOp-BLC module; conducted item reduction; examined the psychometric properties of the resultant items for reliability, validity, and clinical interpretability; and conducted cognitive debriefing interviews to assess the tool’s performance. Results: A total of 150 BLC patients contributed to psychometric validation. We identified and defined eight BLC-specific module items (blood in urine, leaking urine, frequent urination, urinary urgency, burning with urination, constipation, changes in sexual function, and stomal problems). We included those 8 items in addition to 13 MDASI core symptoms and 6 interference items to form the MDASI-PeriOp-BLC module. Cronbach alphas were 0.89 and 0.90 for the 21 severity items and the 6 interference items, respectively. Test–retest reliability (intra-class correlation) was 0.92 for the 21 severity items. The MDASI-PeriOp-BLC module significantly differentiated the patients by performance status (p < 0.0001). Conclusions: The MDASI-PeriOp-BLC is a valid, reliable, and concise tool for monitoring symptom burden during perioperative care in BLC patients undergoing radical cystectomy.

Muscle-invasive bladder cancer (BC) often occurs in patients with competing mortality risks, while also being associated with the highest rate of second primary nonurothelial cancers (SNUC) of all solid malignancies. We investigated the incidence, risk factors, and timing of SNUC as a competing mortality risk factor in patients with BC who were treated with curative intent radical cystectomy (RC).We performed a retrospective cohort study assessing patients who underwent RC for cT2-4 N0M0 BC from January 1, 2005 to December 31, 2018 at a single, high volume tertiary care referral center. The Fine-Gray multivariable regression model was used to evaluate predictive factors for SNUC. Cumulative incidence of mortality (CIM) was estimated with modified Kaplan-Meier analysis.The median follow-up time for the 693 patients who underwent RC was 3.7 years (interquartile range [IQR] 1.9-5.9 years). SNUC developed in 85 (12.3%) patients at a median 3.0 years post-RC (IQR 1.2-5.5 years). On multivariable analysis, the only significant predictor for developing SNUC was freedom from BC recurrence or metastasis (HR 1.54, 95% CI 1.12-1.76, P = 0.019). The most common SNUCs were primary lung cancer (24, 3.2% of cohort) and colon cancer (9, 1.3% of cohort). BC surveillance imaging diagnosed SNUC in 35/52 (67.3%) patients with solid-organ visceral primaries. The overall mortality rate for any SNUC was 38.8%, with the 3 most lethal cancer types being pancreatic, lung, and colon (62.5%, 54.2%, and 44.4% mortality, respectively). The incidence of SNUC uniformly increased postoperatively, with a cumulative incidence of 22.1% (95% CI, 16.8-27.9%) at 12-years post-RC. 163 patients (23.5%) died from BC, 33 patients (4.8%) died from SNUC, and 94 patients (13.6%) died from other causes. While the CIM for BC plateaued around 5-years post-RC at 24%, the incidence of other-cause mortality uniformly rose throughout the postoperative period. By post-RC year 9 there was no significant difference in CIM between BC (CIM 27.2%, 95% CI, 23.5-31.1%) and other-causes (CIM 20.0%, 95% CI, 15.8-24.6%).The cumulative incidence of SNUC at 12-years post-RC was 22%, with the majority identified on BC surveillance imaging. While BC mortality plateaued around 5-years post-RC, mortality related to SNUC or other causes rose steadily in the postoperative period. These data have clinical significance with regards to patient counseling, survivorship and oncologic surveillance in the highly comorbid muscle-invasive BC population.

OBJECTIVE To evaluate the impact of upper tract urothelial carcinoma (UTUC) on bacillus Calmette-Guerin (BCG) response and progression in patients with non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS We performed an institutional review board-approved review of patients with NMIBC treated with adequate intravesical BCG, as defined by the US Food and Drug Administration, at our institution between 2000 and 2018. Patients were stratified by presence of any UTUC and time of UTUC diagnosis (preceding vs synchronous to NMIBC diagnosis or metachronous disease after NMIBC diagnosis). Descriptive statistics were used to summarize the data overall and by groups, and t-tests or Wilcoxon's rank sum tests and Pearson's chi-squared or Fisher's exact tests were used to analyse continuous and categorical data, respectively. RESULTS Of 541 patients with NMIBC treated with adequate BCG, 59 (10.9 %) were diagnosed with UTUC. Of these, 34 had a history of UTUC prior to NMIBC (UTUC-P; median [interquartile range {IQR}] 13.1 [7.4-27.6] months prior), while 25 developed UTUC after diagnosis of NMIBC (six synchronous and 19 metachronous; median [IQR] 12.1 [1.7-28.1] months after). Compared to the non-UTUC group, patients with UTUC-P were more likely to exhibit Tis without papillary tumour in the bladder (20.6% vs 5.0%; P < 0.001), but were less likely to have T1 disease on index transurethral resection (8.8% vs 49.4%; P < 0.001). Patients with UTUC-P developed more recurrences (55.9% vs 34.0%; P = 0.010), any stage/grade progression (23.5% vs 9.8%; P = 0.012) and progression to muscle-invasive or metastatic disease (17.6% vs 6.4%; P = 0.014). The presence of high-grade UTUC-P compared to low-grade UTUC-P was associated with increased NMIBC recurrence (68.2% vs 25.0%; P = 0.049). There was no significant difference in rates of recurrence or progression based on timing of UTUC with respect to the index bladder tumour, although this analysis was limited by small numbers. CONCLUSIONS Presence of UTUC prior to a diagnosis of NMIBC was associated with an almost twofold increased recurrence and progression rates after adequate BCG therapy. This should be considered when counselling patients and designing cohorts for clinical trials.

OBJECTIVES To evaluate if the obesity paradox, wherein obesity portends worse overall prognosis for a disease but improved outcomes for patients receiving immunotherapy, exists for patients receiving bacillus Calmette-Guerin (BCG) in a contemporary cohort. PATIENTS AND METHODS We performed an Institutional Review Board-approved database review to identify patients with non-muscle-invasive bladder cancer (NMIBC) completing at least an induction course of BCG. Clinicopathological variables collected included: body mass index (BMI), medications, and diabetes mellitus (DM). Outcomes of interest included: recurrence-free (RFS), progression-free (PFS), cancer-specific (CSS), and overall survival (OS). Univariate and multivariate modelling were used to evaluate the association between outcomes and clinical factors. RESULTS A total of 579 patients (median follow-up 4.6 years) received BCG induction for NMIBC; 90% had high-grade disease (47.2% clinical stage T1). In all, 75.7% of patients were overweight or obese and 18% had DM. Aspirin, statins, metformin and β-blockers were used in 34%, 42%, 11%, and 29% of patients, respectively. Overweight and obese patients had improved PFS, CSS and OS. DM was associated with worse RFS. Medications of interest had no association with outcomes. CONCLUSION Elevated BMI is associated with improved outcomes in patients with NMIBC treated with BCG immunotherapy. Patients with DM are at increased risk of recurrence. These findings support a potential obesity paradox in bladder cancer. Evaluation of the underlying mechanism and the role of global patient assessment, counselling, and risk factor modification are warranted.

Background Cancer-related changes in sexual function (SF) negatively impact quality of life and intimate partner relationships. There is a lack of data regarding SF among patients who underwent radical cystectomy (RC). Aim To comparatively evaluate perioperative SF among patients who underwent RC. Methods A prospective cohort of 150 patients undergoing RC for bladder cancer and participating in an internal validation study at a single institution from 2016 to 2019 were eligible for analysis. The European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire–Bladder Cancer Muscle Invasive (EORTC QLQ–BLM 30) and Functional Assessment of Cancer Therapy–Bladder were administered; those completing the SF subscale of the EORTC QLQ–BLM 30 were included in final analysis. Analysis was performed using descriptive statistics and generalized linear modeling. Outcomes The primary outcome was interest or engagement in sexual activity within 4 weeks of survey completion, whereas the secondary outcome was a mean score on the EORTC QLQ–BLM 30 SF subscale. Results Overall, 132 of 150 (88%) of patients were eligible, of whom 82% were male, and the median age was 68.5 years. 53% reported at least a little interest in sexual activity, and 40% endorsed sexual activity within the last 4 weeks. The mean SF subscale score was 61.5 ± 25.2. Women had significantly worse mean scores of 72.9 ± 27.1 versus 59.1 ± 24.2 for men (P = .02). On multivariate analysis, both age and female gender were independently associated with higher SF domain scores. Clinical Implications A substantial portion of patients who underwent RC endorse being sexually active or express interest in sexually activity in the perioperative period. Given the recent increase in attention given to SF outcomes and quality of life, this work supports further efforts to explore this area and develop novel interventions to improve outcomes. Strengths and Limitations Strengths include rigorously collected, cross-sectional data using standardized methodology. Limitations include a relatively small sample size of female patients and unknown meaningful clinical difference. Conclusions A substantial portion of patients report sexual interest and activity in the perioperative period; however, female gender is associated with worse SF domain scores. These findings support further inquiry into this topic.

To perform a comparison of complications following open versus robot-assisted radical cystectomy (RC) among women who undergo the procedure. Studies comparing robotic to open RC have been mixed without a clear delineation of which patients benefit the most from one modality vs. the other, leading to continued debate.This was a retrospective study of women who underwent either open or robotic RC at the MD Anderson Cancer Center from 1/2014 to 6/2018. Co-morbidities, pathologic data, and complications were assessed with descriptive statistics, along with uni- and multivariable logistic regression.122 women underwent either open (n = 76) or robotic (n = 46) RC. Open RC was associated with greater intraoperative blood loss (median EBL 775 ml vs. 300 ml, P0.001). In both uni- and multivariable analyses, open RC was associated with a greater odds of intraoperative transfusion compared to robotic RC (odds ratio 6.49, 95% CI 2.85-14.78, P0.001). Women undergoing open RC were also at greater odds of receiving 4 or more units of packed red blood cells (odds ratio 5.46 (1.75-17.02), P = 0.003). Robotic RC conferred a higher median lymph node yield (27 vs. 20 nodes, P,0.001) and operative times (median 513 min vs. 391.5 min, P0.001). There were no differences in margin positivity, length of stay, or readmission rates at 30 and 90 days.Robotic RC was associated with a significantly lower risk of transfusion and EBL, and a higher median lymph node yield and operative time. Unique anatomic considerations may in part be responsible for these findings.

Renal function dictates sequencing and eligibility for definitive therapy in upper tract urothelial carcinoma. We investigated longitudinal glomerular filtration rate (GFR) changes after neoadjuvant chemotherapy (NAC) and nephroureterectomy (RNU).Patients treated with ≥3 cycles of chemotherapy prior to RNU for UTUC from 2000 to 2019 were included. GFR was calculated by CKD-Epi before chemotherapy, before RNU, 1 to 3 months, and 12 months post-RNU. Pathologic stage and overall survival were compared in those with stable GFR (+/-10% of baseline) to the rest of the cohort.One hundred and fifty-two patients received ≥3 cycles of NAC, with 121 (79%) receiving at least 1 cycle of cisplatin. Renal function dropped by mean of 22.3 ml/min/1.73 mIn patients managed with NAC prior to RNU, renal function stabilizes at 1 to 3 months post-operatively and remains clinically similar for cisplatin or non-cisplatin-based therapy. Improvement in GFR during NAC was associated with higher pathologic stage and poorer survival, especially in those receiving non-cisplatin-based therapy, an observation that requires further investigation.

OBJECTIVE Previous reports attempting to evaluate the clinical efficacy of intravesical bacillus Calmette-Guerin (BCG) therapy in patients taking fibrin clot inhibitors (FCI) have yielded conflicting results and are primarily based on patient cohorts treated with only induction BCG. As a result, patients may receive conflicting instructions about whether or not to stop FCIs prior to BCG therapy. We aim to determine the impact of FCI use on oncological outcomes in a large contemporary cohort of patients with non-muscle-invasive bladder cancer (NMIBC) treated with adequate BCG. PATIENTS AND METHODS We performed an institutional review board-approved review of patients with NMIBC treated with adequate intravesical BCG, at our institution between 2000 and 2018. Fibrin clot inhibitor use at the time of BCG therapy was recorded for each patient. Patients were stratified according to use of FCI medication. Recurrence- and progression-free survival were analysed using Kaplan-Meier methods and Cox proportional hazard models. RESULTS Overall, 226 of 526 patients (43.0%) used a FCI: aspirin (n=205), clopidogrel (n=38), warfarin (n=18) and novel oral anticoagulant (NOAC; n=7). The use of FCIs did not adversely affect either recurrence- or progression-free survival (p=0.385 and p=0.131 respectively). These results did not change when the impact of aspirin, clopidogrel or warfarin/NOAC use on recurrence and progression was evaluated separately. On multivariate analysis, FCI use was neither associated with tumour recurrence nor progression. CONCLUSION The use of fibrin clot inhibitors was not associated with adverse oncological outcomes in a large contemporary cohort of patients receiving adequate intravesical BCG for non-muscle invasive bladder cancer. Based on these results, fibrin clot inhibitors may be safely continued during BCG immunotherapy.

Objective The global bacillus Calmette-Guerin (BCG) shortage has prompted the use of alternative treatment strategies for patients with intermediate- and high-risk non-muscle invasive bladder cancer (NMIBC). One such strategy is split-vial dosing which allows several patients to be treated from a single vial of BCG. We evaluated the impact of one-third dose BCG on oncological outcomes in a large cohort of patients with NMIBC treated with adequate BCG in a real-world setting. Patients and methods We performed an institutional review board-approved review of patients with NMIBC treated with adequate BCG at our institution between 2000 and 2020. Patients were stratified according to whether they had received one-third dose (1/3D) BCG or full dose (FD) BCG. Time to recurrence, time to progression and cancer-specific survival were estimated using Kaplan-Meier methods. Results Of 563 patients with NMIBC treated with adequate BCG, 150 (26.6%) received 1/3D and 413 (73.4%) received FD. The use of 1/3D BCG did not adversely affect time to recurrence (p=0.449) or time to progression (p=0.716), and this remained consistent when patients were stratified by individual 2021 EAU prognostic factor risk groups. Cancer-specific survival was similar between patients receiving 1/3D and FD BCG (p=0.320). Conclusion The use of 1/3D BCG was not associated with adverse oncological outcomes in a large cohort of patients receiving adequate BCG for intermediate- and high-risk NMIBC. Based on this real-world experience, risk-stratified split-vial dosing may represent a valuable approach for other institutions facing BCG shortages whilst also providing reassurance to patients who may be concerned about suboptimal outcomes.

While lymph node dissection (LND) at radical cystectomy (RC) for muscle-invasive bladder cancer has been studied extensively, the role of LND for nonmuscle-invasive bladder cancer (NMIBC) remains incompletely defined. Herein, we aim to assess the association between extent of LND during RC for NMIBC and local pelvic recurrence-free survival (LPRS), cancer-specific survival (CSS) and overall survival (OS).A multi-institutional retrospective review was performed of patients with NMIBC undergoing RC at 3 large tertiary referral centers. To identify a threshold for lymph node yield (LNY) to optimize LPRS, CSS and OS, separate Cox regression models were developed for each possible LNY threshold. Model performance including Q-statistics and hazard ratios (HRs) were used to identify optimal LNY thresholds.A total of 1,647 patients underwent RC for NMIBC, with a median LNY of 15 (quartiles 9,23). Model performance curves suggested LNY of 10 and 20 to optimize LPRS and CSS/OS, respectively. On multivariable regression, LNY10 was associated with lower risk of LPR compared to LNY ≤10 (HR 0.63, 95% CI 0.42-0.93, p=0.02). Similarly, LNY20 was associated with improved CSS (HR 0.67, 95% CI 0.52-0.87, p=0.002) and OS (HR 0.75, 95% CI 0.64-0.88, p0.001) compared to LNY ≤20. Similar results were observed in the cT1 and cTis subgroups.Greater extent of LND during RC for NMIBC is associated with improved LPRS, CSS and OS, supporting the inclusion of LND during RC for NMIBC, particularly among patients with cTis or cT1 disease. Future prospective studies are warranted to assess the ideal anatomical template of LND in NMIBC.

Background For some laparoscopic procedures, deep neuromuscular block has been shown to facilitate lower insufflation pressures and lower patient pain scores, and enhance postoperative recovery. We investigated the impact of deep neuromuscular block and its reversal on postoperative shoulder pain and outcomes after robotic prostate surgery. Methods Elderly men undergoing robotic prostatectomy were randomised to deep neuromuscular block (target post-tetanic twitch of 1–2 at the facial nerve) with sugammadex reversal or moderate neuromuscular block (target 1–2 train-of-four ratio) with neostigmine reversal. The primary endpoint was postoperative shoulder pain. The secondary endpoints included intraoperative insufflation pressure, surgical rating score, incidence of residual neuromuscular block, and postoperative recovery. Results A total of 50 subjects for each treatment arm were included in the analysis. The degree of neuromuscular block had no effect on the incidence of shoulder pain (deep block group 12% vs moderate block group 10%; P=1.0) or average insufflation pressure (median [inter-quartile range]) (13.3 [12.5–13.6] mm Hg vs 13.3 [11.7–14] mm Hg, P=0.86). After surgery, the deep block group had a higher normalised train-of-four ratio (0.98 [0.79–1.11] vs 0.85 [0.74–1.00]; P=0.008). The presence of postoperative shoulder pain was associated with higher BMI (31.8 [28–33.9] kg m−2 vs 28 [24.8–31.1] kg m−2; P=0.036) and longer insufflation time (186 [156–257] min vs 154 [126–198] min; P=0.028). Conclusions The use of deep neuromuscular block during surgery does not decrease postoperative shoulder pain or enhance recovery after robotic prostatectomy. Clinical trial registration NCT03210376.

Background Health-related quality of life is important for patients undergoing radical cystectomy (RC). Objective To determine the cost-effectiveness of robotic-assisted RC (RARC) compared to open cystectomy (OC) for bladder cancer and factors that contribute to cost-effectiveness. Design, setting, and participants A decision analytic model was used to compare health-related quality of life and medical costs for RARCs with intracorporeal urinary diversion and OCs performed between 2007 and 2015. Outcome measurements and statistical analysis Propensity matching was performed among 1322 cases to yield a final cohort of 100 RARC and 96 ORC cases. Probabilities were obtained from the clinical study data, while quality-adjusted life years (QALYs) and health utility values were derived from the literature. A complication, readmission, or transfusion was included in the 90-d time horizon model. Results and limitations There were no differences between the groups in patient demographics, pathologic staging, or length of stay. Multivariable analysis revealed that the RARC group had fewer transfusions and complications compared to the OC group. The incremental cost-effectiveness ratio was $2969. RARC cost $2969 less per QALY when compared to OC. While RARC was $17000 more expensive, it also associated with an increase of 0.32 QALYs. One-way sensitivity analysis identified RARC as the preferred strategy if a complication can be prevented 74% of the time. RARC is preferred as long as it is 70% effective in preventing a transfusion. Two-way sensitivity analysis showed that as long as RARC can prevent complications and transfusions, it is the preferred cost-effective treatment when compared to OC. The study is limited by the omission of a societal perspective and the lack of health utility values for RC. Conclusions RARC is cost-effective compared to OC when the rates of complications and transfusions are significantly lower. Patient summary Bladder removal via a robotic approach is more expensive, but it improves health-related quality of life. Robotic surgery is cost-effective compared to an open approach for bladder removal if there are low rates of complications and blood transfusion.

BACKGROUND The purpose of this study was to assess treatment choices among men with prostate cancer who presented at The University of Texas MD Anderson Cancer Center multidisciplinary (MultiD) clinic compared with nationwide trends. METHODS In total, 4451 men with prostate cancer who presented at the MultiD clinic from 2004 to 2016 were analyzed. To assess nationwide trends, the authors analyzed 392,710 men with prostate cancer who were diagnosed between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. The primary endpoint was treatment choice as a function of pretreatment demographics. RESULTS Univariate analyses revealed similar treatment trends in the MultiD and SEER cohorts. The use of procedural forms of definitive therapy decreased with age, including brachytherapy and prostatectomy (all P

Tumors that recur after bacillus Calmette-Guerin (BCG) therapy are considered to be of very high risk, and patients are often recommended to undergo radical cystectomy (RC). However, the nuances associated with the grade of tumor recurrence after BCG treatment are not well understood.To characterize the pattern of bladder cancer progression and cancer-specific survival (CSS) in patients with recurrences dichotomized by low grade (LG) versus high grade (HG) after intravesical BCG treatment, and to assess the safety of continued bladder-sparing therapy in these patients.We performed an Institutional Review Board-approved review of our bladder cancer database. Overall, 146 non-muscle-invasive bladder cancer (NMIBC) patients were found to have NMIBC recurrence while on BCG therapy; this recurrence was LG in 38 and HG in 108. Baseline clinicopathologic characteristics including age, gender, primary tumor grade, stage, size, multiplicity, and concurrent carcinoma in situ were also evaluated. The primary endpoint was progression-free survival (PFS), with progression defined as the development of muscle-invasive bladder cancer (MIBC)/distant metastasis. In addition, recurrence-free survival (RFS), HG RFS, cystectomy-free survival (CFS), and CSS were also compared. Multivariable analysis was performed using the Cox regression model. All tests were two sided, and p0.05 was considered statistically significant.Further intravesical therapy versus salvage RC.Overall, estimated 5-yr PFS was 72.4% (95% confidence interval [CI] 60.4-81.3%). As dichotomized by grade of recurrent tumor, PFS was greater for patients with LG recurrences (85.6%, 95% CI 60.8-95.2%) than for those with HG recurrence (67.9%, 95% CI 54.1-78.4%; p=0.010). Furthermore, patients whose initial recurrence on BCG therapy was LG had improved subsequent RFS (median 62 vs 34mo, p=0.007), HG RFS (median 112 vs 36mo, p0.001), and CFS (estimated 5-yr CFS 80.8% vs 49.8%, p0.001) compared with those who had HG initial recurrence. On univariate and multivariate analyses, grade of tumor recurrence after BCG was an independent predictor of time to progression to MIBC/distant metastasis (hazard ratio 3.60, 95% CI 1.18-10.94, p=0.024).Grade of tumor recurrence after intravesical BCG is an important predictor of bladder cancer progression to MIBC/metastatic urothelial carcinoma. While, patients with LG recurrences have less than half the progression events compared with those with HG recurrences, their estimated 5-yr progression rate is still 14.4%. Hence all patients should be carefully counseled on bladder-sparing therapy. This also has implications for clinical trial design.If bladder cancer recurs after bacillus Calmette-Guerin treatment, there are many factors that determine the further clinical outcome. Although low-grade recurrent tumors confer a less aggressive course, disease progression can still occur, and hence continued vigilance is important.

INTRODUCTION AND OBJECTIVE:Following a diagnosis of non-muscle invasive bladder cancer (NMIBC), patients are at risk for developing upper tract urothelial carcinoma (UTUC). Guidelines vary on the f...

INTRODUCTION AND OBJECTIVE:Guideline indications for restaging transurethral resection (reTUR) for high-grade (HG) Ta bladder tumors vary due to a paucity of data. Herein, we investigate Guideline-...

INTRODUCTION AND OBJECTIVE:Current risk tables for outcome prediction in patients with non-muscle invasive bladder cancer (NMIBC) are based upon studies comprised primarily of low-grade tumors. We ...