M0 Bladder Cancer Research Articles

(285) Evaluation of Penile Prosthesis Implantation in Older Adults with Bladder Cancer After Radical Cystectomy

Abstract Introduction Erectile dysfunction (ED) is common after radical cystectomy (RC), but ED treatment in this setting remain understudied. Many such patients will be unresponsive to oral pharmacotherapy, often requiring penile prosthesis (PP) implantation. Objective The objective of this study was to evaluate PP implantation in a contemporary, national cohort of older adults with bladder cancer following RC. Methods We used the SEER-Medicare database to identify male patients 66 years and older diagnosed with Tany Nany M0 bladder cancer from 2000 to 2017 and treated with RC. We estimated time to PP implantation using the Kaplan-Meier method, and evaluated the associations of baseline characteristics with PP implantation using Cox proportional hazard regression. Results The study cohort included 4,468 men who underwent RC, including 75% who were married or had a domestic partner. A total of 334 (7%) patients had baseline ED. Median follow-up after RC was 38.0 (IQR 16.0-84.0) months. After RC, only 71 (2%) patients underwent PP implantation, with a median time to PP implantation of 12 (IQR 5-32) months. In univariable analysis, younger age, black race, and undergoing RC at small bed size hospitals, comprehensive NCI Cancer Centers, higher RC volume hospitals, and hospitals in the West and South/Southeast regions were associated with higher rates of implantation (Table 1). Disease characteristics were not related to PP implantation. Conclusions Despite the expected prevalence of ED following RC, contemporary, real-world rates of PP implantation are very low. Univariable analyses suggest that both patient characteristics and features of the hospital performing RC are associated with treatment for post-RC ED with PP implantation. Disclosure No.

Impact of the extent of lymph node dissection on survival outcomes in clinically lymph node-positive bladder cancer.

To determine the oncological impact of extended pelvic lymph node dissection (ePLND) vs standard PLND (sPLND) during radical cystectomy (RC) in clinically lymph node-positive (cN+) bladder cancer (BCa). In this retrospective, multicentre study we included 969 patients who underwent RC with sPLND (internal/external iliac and obturator lymph nodes) or ePLND (sPLND plus common iliac and presacral nodes) with or without platin-based peri-operative chemotherapy for cTany N1-3 M0 BCa between 1991 and 2022. We assessed the impact of ePLND on recurrence-free survival (RFS) and the distribution of recurrences (locoregional and distant recurrences). The secondary endpoint was overall survival (OS). We performed propensity-score matching using covariates associated with the extent of PLND in univariable logistic regression analysis. The association of the extent of PLND with RFS and OS was investigated using Cox regression models. Of 969 cN+ patients, 510 were 1:1 matched on propensity scores. The median (interquartile range [IQR]) time to recurrence was 8 (4-16) months, and median (IQR) follow-up of alive patients was 30 (13-51) months. Disease recurrence was observed in 104 patients in the ePLND and 107 in the sPLND group. Of these, 136 (27%), 47 (9.2%) and 19 patients (3.7%) experienced distant, locoregional, or both distant and locoregional disease recurrence, respectively. When stratified by the extent of PLND, we did not find a difference in recurrence patterns (P > 0.05). ePLND improved neither RFS (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.70-1.19; P = 0.5) nor OS (HR 0.78, 95% CI 0.60-1.01; P = 0.06) compared to sPLND. Stratification by induction chemotherapy did not change outcomes. Performing an ePLND at the time of RC in cN+ patients improved neither RFS nor OS compared to sPLND, regardless of induction chemotherapy status. Pretreatment risk stratification is paramount to identify ideal candidates for RC with ePLND as part of a multimodal treatment approach.

The Utility of Inflammatory Serum Markers in the Assessment of Perioperative Morbidity after Radical Cystectomy for Bladder Cancer.

Background and Objectives: To date, sparse evidence exists about the impact of inflammatory serum markers in predicting perioperative complications after radical cystectomy (RC) for bladder cancer (BC). Here, we evaluated the role of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), C-reactive protein (CRP), and plasma fibrinogen in predicting perioperative morbidity and unplanned 30-days readmission after RC for BC. Materials and methods: We relied on a collaborative database of 271 patients who underwent open RC for cT1-4a N0 M0 BC between January 2012 and December 2022. Univariable and multivariable binomial logistic regression analyses were performed to assess the odds ratio (OR) with 95% confidence intervals (CI) testing the ability of each serum marker to predict postoperative complications (any-grade and major complications), and 30-days unplanned readmission. Results: The median age at RC was 73 yr (IQR 67-79). A total of 182 (67.2%) patients were male and the median BMI was 25.2 (IQR 23.2-28.4). Overall, 172 (63.5%) patients had a Charlson Comorbidity Index (CCI) greater than 2 points and 98 (36.2%) were current smokers at the time of RC. Overall, 233 (86.0%) patients experienced at least one complication after RC. Of these, 171 (63.1%) patients had minor complications (Clavien-Dindo grade 1-2) while 100 (36.9%) experienced major complications (Clavien-Dindo grade ≥ 3). According to multivariable analysis, current smoking status, high plasma fibrinogen, and preoperative anemia were independently associated with major complications (OR 2.10, 95%CI 1.15-4.90, p = 0.02), (OR 1.51, 95%CI 1.26-1.98, p = 0.09), and (OR 1.35, 95%CI 1.17-2.57, p = 0.03), respectively. Overall, 56 (20.7%) patients experienced a 30-days unplanned readmission. According to univariable analysis, high preoperative CRP and hyperfibrinogenemia were significantly associated with an increased risk of unplanned readmission (OR 2.15, 95%CI 1.15-4.16, p = 0.02; OR 2.18, 95%CI 1.13-4.44, p = 0.02, respectively). Conclusions: In our study, the preoperative immune-inflammation signature described by NLR, PLR, LMR, SII, and CRP showed a low reliability in predicting perioperative course after RC. Preoperative anemia and hyperfibrinogenemia were independent predictors of major complications. Further studies are pending in order to draw definitive conclusions.

V08-03 INDIANA POUCH CONTINENT CUTANEOUS URINARY DIVERSION AFTER ROBOTIC-ASSISTED RADICAL CYSTECTOMY: A 16-YEAR EXPERIENCE

You have accessJournal of UrologyCME1 Apr 2023V08-03 INDIANA POUCH CONTINENT CUTANEOUS URINARY DIVERSION AFTER ROBOTIC-ASSISTED RADICAL CYSTECTOMY: A 16-YEAR EXPERIENCE Albert Kim and Kevin Chan Albert KimAlbert Kim More articles by this author and Kevin ChanKevin Chan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003306.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Continent urinary diversion after radical cystectomy is an underutilized option even at high-volume centers with studies demonstrating socio-economic, geographical, and gender disparities. Efforts to optimize utilization of continent diversion must concentrate on changing perceptions regarding feasibility and accurate reporting of complications.The objective of this study is to report long-term clinical outcomes in bladder cancer patients receiving an Indiana pouch continent cutaneous urinary diversion (CCUD) after robot-assisted radical cystectomy. METHODS: After Institutional Review Board approval, a prospectively maintained bladder cancer database was queried for patients with T1-T4, N0-N1, M0 bladder cancer undergoing radical cystectomy with CCUD at a tertiary referral center from 2004 to 2020. Complications at 30- and 90-days were recorded according to the Clavien-Dindo classification. Continence rates were recorded by manual chart review. RESULTS: A total of 97 patients were included with a median follow-up of 93 months. Clinically, 91.8% had £T2 disease and 29.9 % received neoadjuvant chemotherapy. The median length of surgery was 8.0 hours, length of hospital stay was 8.3 days, and urinary continence rate was 99.0%. The overall complication rate was 73.2% and 76.5% at 30- and 90-days respectively. Most complications were low grade (Clavien I or II). Acute blood loss anemia and symptomatic urinary tract infection were the most common low grade complications. The major complication rate was 17.5% at 30-days and 22.7% at 90-days. The most common major complications were abdominal infection requiring percutaneous drain placement, Clavien Grade III, and uretero-colonic stricture requiring percutaneous nephrostomy tube placement and surgical revision, Clavien Grade III. The readmission rate was 21.4% and median overall survival was 108 months. CONCLUSIONS: CCUD provides exceptional functional outcomes with acceptable complication rates compared to other diversion types. Source of Funding: NONE Disclosures: NONE © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e749 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Albert Kim More articles by this author Kevin Chan More articles by this author Expand All Advertisement PDF downloadLoading ...

Carboplatin Induction Chemotherapy in Clinically Lymph Node–positive Bladder Cancer

BackgroundThere are currently no guideline recommendations regarding the treatment of cisplatin-ineligible, clinically lymph node–positive (cN+) bladder cancer (BCa). ObjectiveTo investigate the oncological efficacy of gemcitabine/carboplatin induction chemotherapy (IC) in comparison to cisplatin-based regimens in cN+ BCa. Design, setting, and participantsThis was an observational study of 369 patients with cT2–4 N1–3 M0 BCa. InterventionIC followed by consolidative radical cystectomy (RC). Outcome measurements and statistical analysisThe primary endpoints were the pathological objective response (pOR; ypT0/Ta/Tis/T1 N0) rate and the pathological complete response (pCR; ypT0N0) rate. We applied 3:1 propensity score matching (PSM) to reduce selection bias. Overall survival (OS) and cancer-specific survival (CSS) were compared across groups using the Kaplan-Meier method. Associations between the treatment regimen and survival endpoints were tested in multivariable Cox regression analyses. Results and limitationsAfter PSM, a cohort of 216 patients was available for analysis, of whom 162 received cisplatin-based IC and 54 gemcitabine/carboplatin IC. At RC, 54 patients (25%) had a pOR and 36 (17%) had a pCR. The 2-yr CSS was 59.8% (95% confidence interval [CI] 51.9–69%) for patients who received cisplatin-based IC versus 38.8% (95% CI 26–57.9%) for those who received gemcitabine/carboplatin. For the pOR (p = 0.8), ypN0 status at RC (p = 0.5), and cN1 BCa subgroups (p = 0.7), there was no difference in CSS between cisplatin-based IC and gemcitabine/carboplatin. In the cN1 subgroup, treatment with gemcitabine/carboplatin was not associated with shorter OS (p = 0.2) or CSS (p = 0.1) on multivariable Cox regression analysis. ConclusionsCisplatin-based IC seems to be superior to gemcitabine/carboplatin and should be the standard for cisplatin-eligible patients with cN+ BCa. Gemcitabine/carboplatin may be an alternative treatment for selected cisplatin-ineligible patients with cN+ BCa. In particular, selected cisplatin-ineligible patients with cN1 disease may benefit from gemcitabine/carboplatin IC. Patient summaryIn this multicenter study, we found that selected patients with bladder cancer and clinical evidence of lymph node metastasis who cannot receive standard cisplatin-based chemotherapy before surgery to remove their bladder may benefit from chemotherapy with gemcitabine/carboplatin. Patients with a single lymph node metastasis may benefit the most.

Clinical Outcomes in cN+M0 Bladder Cancer Patients: Can Bladder be Spared?

<h3>Purpose/Objective(s)</h3> Optimum management of patients initially presenting with clinically node positive non-metastatic (cN+M0) bladder cancer is a topic of debate with significant variation in practice worldwide. In the UK, fit patients are offered – after platinum-based chemotherapy - either radical cystectomy (RC) or radical radiotherapy (RadRT) – a bladder preserving treatment. There is a paucity of evidence to guide clinician and patient decision making on choice of treatment. A multi-center UK retrospective analysis was undertaken to assess clinical outcomes for cN+M0 bladder cancer. <h3>Materials/Methods</h3> A multicenter retrospective analysis was conducted on patients from four large UK Oncology Centers. Patients initially presenting with cN+M0 bladder cancer between 2012 and 2021 were identified. Data was collected on treatment received, clinical outcomes and patient and tumor factors. Overall survival (OS) was calculated as time from initial diagnosis of bladder cancer. Univariable and multivariable analysis was performed on patients receiving radical treatment using the variables; age, performance status (PS), T and N stage, primary chemotherapy and radical treatment received. <h3>Results</h3> 288/292 patients with cN+M0 bladder cancer identified had survival data available for analysis. Median OS of the whole analyzed cohort (n=288) was 1.54 years (95% CI 1.35-1.82). 163/288 patients received a treatment with radical intent. OS was significantly higher in the radical vs palliative treatment group (log-rank test, p<0.0001). Median OS in the radical and palliative groups were 2.41 years (95% CI,1.92-2.78) and 0.89 year (95% CI, 0.68-1.07) respectively. Patients treated radically received either RC (n=76) or RadRT (n=87) with no difference is OS between the two groups (log-rank test p=0.5). Median OS for those receiving RadRT was 2.53 years (95% CI, 2.02-3.44) vs 2.09 years (95% CI, 1.79-3.13) for RC. In a univariable analysis of patients receiving radical treatment, improved OS was positively associated with lower PS (HR 0.61 (95% CI 0.41-0.91) p=0.02), lower T stage (HR 0.59 (95% CI 0.37-0.95) p=0.03) and receiving primary chemotherapy (HR 0.6 (95% CI 0.4-0.9) p=0.01). No variables retained significance on multivariable analysis. <h3>Conclusion</h3> This multi-center retrospective analysis of survival outcomes gives real-world data on a large cohort of patients with cN+M0 bladder cancer. A limitation of our data is the risk of confounders when comparing retrospective cohorts. Overall survival unfortunately remains poor in this cohort but was significantly longer in patients who received radical-intent treatment. There was no difference in overall survival between patients receiving RC and RadRT. Given the equivalent survival outcomes in these patients whose overall prognosis remains poor, our data would support wider use of radiotherapy to avoid risks from major surgery in node-positive patients.

Outcomes in Clinically Node Positive Bladder Cancer Patients at a Tertiary Cancer Centre in the UK

Purpose: Poor prognosis TxN+M0 bladder cancer has limited evidence-based guidelines defining optimum management. We evaluated real-world outcomes and treatment approaches for patients at a tertiary oncology centre.

Neoadjuvant versus adjuvant chemotherapy for muscle-invasive bladder cancer: a propensity matched analysis.

BACKGROUND We compared survival outcomes among patients who received either NAC or AC and RC. METHODS We identified patients in the National Cancer Data Base (NCDB) diagnosed with clinical T2-T4, N0, M0 urothelial carcinoma who underwent RC. Patients who received NAC were propensity matched by age, race, ethnicity, sex, insurance type, academic/research program, comorbidity, and clinical stage to patients receiving AC within 90 days of RC. Median survival was calculated using Kaplan-Meier analysis. Adjusted hazard ratios (aHR) and 95% confidence intervals (95% CI) were calculated from multivariable Cox regression models to compare overall survival (OS), downstaging to non-MIBC (NMIBC), and N upstaging. RESULTS A total of 417 patients treated with NAC and 272 patients treated with AC were identified from 2004-2013. Patients who received NAC had better 5-year OS (46.2%, 95% CI: 39.2-53.0%) compared to patients who received AC (37.6%, 95% CI: 31.5-43.7%). NAC was a significant predictor of decreased mortality, decreased progression to node positivity, and downstaging to NMIBC (0.76, 0.60-0.96, P=0.023; 0.19, 0.13-0.28, P<0.001; 23.96, 8.91-64.42, P<0.001). CONCLUSIONS The use of NAC+RC was associated with improved OS compared to RC+AC for patients diagnosed with T2-T4, N0, M0 bladder cancer. The increased survival benefit associated with NAC compared to AC among patients undergoing RC may be due to decreased progression to node positivity and pathological downstaging.

Neoadjuvant chemotherapy in bladder cancer: Clinical benefit observed in prospective trials computed with restricted mean survival times

PurposeNeoadjuvant chemotherapy (NAC) is the standard of care for eligible patients with cT2-4a N0 M0 bladder cancer undergoing surgical resection. The extent to which (and if) NAC increases patient survival is not clear as clinical trials and meta-analyses have generated both negative and “borderline” positive results. The novel method of calculating restricted mean survival times (RMST) may provide a more meaningful way to quantify treatment efficacy due to inherent statistical limitations of conventional hazard ratios. In this study we analyzed the survival benefit attributable to NAC in bladder cancer by calculating RMST of previously published clinical trials. Materials and methodsAll published randomized controlled clinical trials of bladder cancer with available survival data comparing NAC plus radical cystectomy with cystectomy alone were included. RMSTs were calculated for each cohort at the 5-year and total follow-up time periods, comparing the NAC and radical cystectomy groups. Fixed effect meta-analysis of the 5-year RMSTs was then performed to calculate the net impact of NAC on overall survival. ResultsFor 2 among 7 included trails, RMST analysis changed the statistical significance. The SWOG 8,710 trial that had previously suggested a survival benefit associated with NAC (P = 0.06) was found to have a clearer beneficial association by 5-year RMST (6.5 month benefit; P = 0.01) and total follow-up RMST (13.6 month benefit over 168 months; P = 0.04). The International Collaboration of Trialists trial that had previously suggested a survival benefit with NAC (P = 0.04) was found to have a beneficial association by total follow-up RMST (6.7 months benefit over 120 months; P = 0.04) but not 5-year RMST (P = 0.10). The interpretation of other trials did not change. Fixed effect meta-analysis suggested a clinically significant overall survival benefit associated with NAC (3.2 months benefit over 60 months; P < 0.01). ConclusionsEvaluation of published randomized controlled trials using RMSTs strengthens the association of neoadjuvant chemotherapy with survival benefit in bladder cancer. As RMST may enable improved detection of clinical benefit when compared to conventional statistical methods, consideration should be given to RMST-based endpoints in future clinical trial design.

Concurrent Durvalumab And Radiation Therapy (DUART) followed by Adjuvant Durvalumab in Patients with Localized Urothelial Cancer of Bladder: BTCRC-GU15-023

Bladder cancer (BC) patients (pts) who are cisplatin ineligible/unfit for surgery or unresectable have limited treatment options. In this study, we investigate if the combination of radiation therapy (RT) and checkpoint inhibitor, durvalumab (durva), is safe and effective in these pts. Our results from phase (ph) Ib suggested that the combination was safe. Here we present the updated response rate post durvaRT and updated treatment related adverse events (TRAEs) amongst our evaluable pts in ph II. This is a single arm ph Ib-II study for T2-4 N0-2 M0 BC pts. The ph II primary endpoints a) PFS rate at 1 yr b) disease control rate (DCR); secondary endpoints were a) CR post durvaRT b) PFS c) OS. Pts were treated with durva (1500mg) Q4 wks x2 doses along with definitive RT (64.8Gy, 36 fractions over 7 wks) to the bladder and involved nodes followed by adjuvant durva Q4 wk x 1 yr. Response was evaluated with CT scan and cystoscopy+biopsy post durvaRT. We anticipated that durvaRT followed by durva would increase PFS at 1 yr from 50% to 75% when compared to RT; we assumed DCR of about 75%. A total of 26 pts was needed to reach a statistical power of at least 80% at one-sided alpha of 5% and to allow for 10% drop out rate. Total N = 26 patients (Male 19; Female 7, median age 74yr). Node positive patients were 30.8%. At the time of data cut off (1/2020) 24/26 pts were evaluable for response post durvaRT. 2 pts withdrew from active Rx before 1st response evaluation. Post completion of durvaRT, clinical CR was seen in 17/24 pts (70.8%); PR 3/24 pts (12.5%); SD 3/24 (12.5%); PD 1/21 (4.7%). DCR was seen in 23/24 pts (95.8%) post durvaRT. Mean follow up from D1 to last follow up was 11.2 mos. Grade ≥ 3 TRAE amongst 26 pts: anemia (1/26), lipase/amylase (1/26), immune nephritis (1/26), dyspnea (gr 4- COPD/immune), fatigue (1/26), lymphopenia (6/26). Median no. of doses of durva was 8.0 from D1 (range 2-15); median no. of adjuvant durva doses was 6.0 (range 0-13). DurvaRT followed by durva demonstrated promising efficacy with 95.8% DCR and clinical CR of 70.8% in unresectable, cisplatin ineligible locally advanced BC. Efficacy was also seen in node positive patients. It was generally well tolerated. Ph II study has completed accrual and longer follow up with PFS, OS and DCR post adjuvant treatment will further our understanding of this regimen’s efficacy in locally advanced BC.

Efficacy of carboplatin-based chemotherapy regimens in patients with bladder cancer in the neoadjuvant setting.

e17001 Background: There is paucity of evidence regarding efficacy of neoadjuvant chemotherapy regimens in bladder cancer patients. Radical cystectomy has been standard of care for patients with T2-T4, N0, M0 bladder cancer. However, recent trials have shown better survival rates in patients who underwent neo-adjuvant chemotherapy. Our meta-analysis is based on the data from non-randomized clinical trials on the efficacy of carboplatin based regimens. Methods: We conducted a systematic search of Medline (Pubmed) and Cochrane (from inception through May, 2018). Only published single arm clinical trials, abstracts of single arm clinical trials and data from one randomized trial on efficacy of neoadjuvant Carboplatin based therapies in patients with bladder cancer were included in our meta-analysis. Total of &gt; 70 studies were identified. Studies which were duplicate, included adjuvant therapy, systematic reviews or meta-analysis, trials not based on neoadjuvant therapy were excluded. A random effect model was used to calculate pooled proportions. Studies based on ITT protocol were analyzed separately as well as studies based on per protocol analysis. Comprehensive Meta-Analysis software version 3.0 was used. Results: The pooled proportion of pCR (pathologic complete response) calculated from trials based on ITT analysis was 0.23 (95% CI 0.19 to 0.28, P= 0.000). Tests for statistical heterogeneity was non-significant heterogeneity p-value = 0.79 (I2 = 0 %). The pooled proportion of pCR calculated from trials based on per-protocol analysis was 0.29 (95% CI 0.19 to 0.42, P= 0.002). Tests for statistical heterogeneity show nonsignificant heterogeneity p-value = 0.95 (I2 = 0 %). The pooled proportion of ORR (objective response rate) calculated from trials based on per-protocol analysis was 0.69 (95% CI 0.57 to 0.78, P= 0.001). Tests for statistical heterogeneity showed heterogeneity p-value = 0.203 (I2 = 37.3). The pooled proportion of cCR (clinical Complete response) calculated from trials based on per-protocol analysis was 0.25 (95% CI 0.18 to 0.34, P= 0.000). Tests for statistical heterogeneity did not show heterogeneity p-value = 0.80 (I2 = 0%). The pooled proportion of cPR (clinical Partial Response) calculated from trials based on per-protocol analysis was 0.47 (95% CI 0.39 to 0.56, P= 0.59). Tests for statistical heterogeneity did not show heterogeneity p-value = 0.93 (I2 = 0%). Conclusions: Carboplatin based chemotherapy has shown significant efficacy in terms of over-all response rate, pathologic complete response and clinical complete response.

Impact of Alzheimer's disease and related dementia diagnosis following treatment for bladder cancer

ObjectivesOur objective was to assess the incidence of Alzheimer's Disease and related dementia diagnosis following treatment for muscle-invasive bladder cancer and impact on survival outcomes. Materials and MethodsA total of 4814 patients diagnosed with clinical stage T2-T4a, N0, M0 bladder cancer between January 1, 2002 to December 31, 2011 using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database were identified. Alzheimer's disease and related dementia diagnosis was identified using International Statistical Classification of Disease-Ninth Edition outpatient and inpatient codes. Incidence of dementia following treatment were calculated and reported as dementia cases per 10,000 person-years. Cox proportional hazards models were used to assess the impact of dementia on survival outcomes. ResultsOf the 4814 patients, 2403 (49.9%) underwent radical cystectomy (RC) and 2411 (50.1%) underwent radiotherapy (RTX) and/or chemotherapy (CTX). Overall, 837 (17.4%) patients developed Alzheimer's disease and related dementia following bladder cancer treatment. There was no significant difference in the incidence of Alzheimer's disease and related dementia following either treatment. Patients diagnosed with Alzheimer's disease and related dementia had worse overall (Hazard Ratio (HR), 2.64; 95% Confidence Interval (CI), 2.41–2.89) and cancer-specific (HR, 2.45; 95% CI, 2.18–2.76) survival than those without a dementia diagnosis following treatment. ConclusionWhile we observed no difference in new-onset Alzheimer's disease and related dementia diagnosis following RC or RTX and/or CTX, patients with a Alzheimer's and related dementia diagnosis was associated with worse overall and cancer-specific survival. These findings have important implications for screening and the development of targeted interventions for improving outcomes in older adults following complex cancer treatments, as observed in this bladder cancer population.

Prognosis of patients receiving induction chemotherapy for locally advanced or lymph node metastatic bladder cancer

Background: Induction chemotherapy is recommended before surgery for unresectable muscle-invasive bladder cancer, locally advanced or lymph node disseminated disease. These patients’ prognoses cannot be extrapolated from data regarding neoadjuvant chemotherapy, which is performed in operable patients. Objective: We assessed the prognosis of patients undergoing induction chemotherapy for locally advanced or lymph node metastatic bladder cancer. Methods: We analysed patients with cT4NxM0 or cTxN+M0 bladder cancer treated by induction chemotherapy between 2006 and 2016. The tumour extension and node invasion was determined by imaging or histologically after upfront lymph node dissection. Clinical, biological, pathological and patient follow-up data were identified. Kaplan–Meier survival curves were compared by log rank test. Factors associated with the response to induction chemotherapy, operability of patients and survival were determined by multivariable logistic regression. Results: Among 70 patients included in the analysis, 51 (73%) showed response to induction chemotherapy. Progression-free and overall survival were improved in responder patients compared with non-responders ( P&lt;0.0001 and P=0.025, respectively) and for patients who underwent surgery compared with non-operated patients (both P&lt;0.001). On multivariable analysis, poor response was associated with chemotherapy other than methotrexate, vinblastine, doxorubicin and cisplatin ( P=0.016), operability with late response ( P=0.0024) and overall survival with surgery after induction chemotherapy ( P=0.0014). Conclusions: Surgery after induction chemotherapy with methotrexate, vinblastine, doxorubicin and cisplatin may improve prognosis with locally advanced or lymph node metastatic bladder cancer. Level of evidence: 4

Neoadjuvant versus adjuvant chemotherapy for muscle-invasive bladder cancer: a propensity matched analysis.

We compared survival outcomes among patients who received either NAC or AC and RC. We identified patients in the National Cancer Data Base (NCDB) diagnosed with clinical T2-T4, N0, M0 urothelial carcinoma who underwent RC. Patients who received NAC were propensity matched by age, race, ethnicity, sex, insurance type, academic/research program, comorbidity, and clinical stage to patients receiving AC within 90 days of RC. Median survival was calculated using Kaplan-Meier analysis. Adjusted hazard ratios (aHR) and 95% confidence intervals (95% CI) were calculated from multivariable Cox regression models to compare overall survival (OS), downstaging to non-MIBC (NMIBC), and N upstaging. A total of 417 patients treated with NAC and 272 patients treated with AC were identified from 2004-2013. Patients who received NAC had better 5-year OS (46.2%, 95% CI: 39.2-53.0%) compared to patients who received AC (37.6%, 95% CI: 31.5-43.7%). NAC was a significant predictor of decreased mortality, decreased progression to node positivity, and downstaging to NMIBC (0.76, 0.60-0.96, P=0.023; 0.19, 0.13-0.28, P<0.001; 23.96, 8.91-64.42, P<0.001). The use of NAC+RC was associated with improved OS compared to RC+AC for patients diagnosed with T2-T4, N0, M0 bladder cancer. The increased survival benefit associated with NAC compared to AC among patients undergoing RC may be due to decreased progression to node positivity and pathological downstaging.

Propensity-matched analysis of stage-specific efficacy of adjuvant chemotherapy for bladder cancer

BackgroundContemporary randomized controlled trials exploring adjuvant chemotherapy (AC) for bladder cancer (BCa) have yielded inconsistent results due to premature termination and/or poor patient accrual. ObjectiveTo compare efficacy of AC vs. observation after radical cystectomy stratified by disease stage in a propensity-matched cohort. Design, setting, and participantsWe performed a retrospective study that included patients who underwent radical cystectomy for any pT, N0-1, M0 BCa from the National Cancer Data Base (2004–2014). Patients who underwent AC were 1:1 propensity matched with patients who received observation only. Outcome measurements and statistical analysisOverall survival was assessed with multivariable Cox regression models where adjusted hazard ratios (aHR) and 95% confidence intervals (95% CI) were calculated. Results and limitationsAfter coarsened exact 1:1 propensity matching, 3,066 patients (AC 1,533; observation 1,533) were included in the analysis. There were no significant differences in patient-, facility-, or tumor-level characteristics among cohorts. Compared with patients who underwent observation, recipients of AC had improved overall survival (aHR 0.67; 95% CI 0.61–0.74). Patients with pT2-4, pN1 disease significantly benefited from AC. Among the pN0 cohort, improved survival from AC was observed only in stages pT3 (aHR 0.67; 95% CI 0.55–0.83) and pT4 (aHR 0.70; 95% CI 0.50–0.98). ConclusionsAC was associated with improved survival in locally advanced (pT3-4, pN0) and regionally advanced (pT2-4, pN1) chemotherapy-naive BCa.

Robot-assisted radical cystectomy versus open radical cystectomy in patients with bladder cancer (RAZOR): an open-label, randomised, phase 3, non-inferiority trial

Radical cystectomy is the surgical standard for invasive bladder cancer. Robot-assisted cystectomy has been proposed to provide similar oncological outcomes with lower morbidity. We aimed to compare progression-free survival in patients with bladder cancer treated with open cystectomy and robot-assisted cystectomy. The RAZOR study is a randomised, open-label, non-inferiority, phase 3 trial done in 15 medical centres in the USA. Eligible participants (aged ≥18 years) had biopsy-proven clinical stage T1-T4, N0-N1, M0 bladder cancer or refractory carcinoma in situ. Individuals who had previously had open abdominal or pelvic surgery, or who had any pre-existing health conditions that would preclude safe initiation or maintenance of pneumoperitoneum were excluded. Patients were centrally assigned (1:1) via a web-based system, with block randomisation by institution, stratified by type of urinary diversion, clinical T stage, and Eastern Cooperative Oncology Group performance status, to receive robot-assisted radical cystectomy or open radical cystectomy with extracorporeal urinary diversion. Treatment allocation was only masked from pathologists. The primary endpoint was 2-year progression-free survival, with non-inferiority established if the lower bound of the one-sided 97·5% CI for the treatment difference (robotic cystectomy minus open cystectomy) was greater than -15 percentage points. The primary analysis was done in the per-protocol population. Safety was assessed in the same population. This trial is registered with ClinicalTrials.gov, number NCT01157676. Between July 1, 2011, and Nov 18, 2014, 350 participants were randomly assigned to treatment. The intended treatment was robotic cystectomy in 176 patients and open cystectomy in 174 patients. 17 (10%) of 176 patients in the robotic cystectomy group did not have surgery and nine (5%) patients had a different surgery to that they were assigned. 21 (12%) of 174 patients in the open cystectomy group did not have surgery and one (1%) patient had robotic cystectomy instead of open cystectomy. Thus, 302 patients (150 in the robotic cystectomy group and 152 in the open cystectomy group) were included in the per-protocol analysis set. 2-year progression-free survival was 72·3% (95% CI 64·3 to 78·8) in the robotic cystectomy group and 71·6% (95% CI 63·6 to 78·2) in the open cystectomy group (difference 0·7%, 95% CI -9·6% to 10·9%; pnon-inferiority=0·001), indicating non-inferiority of robotic cystectomy. Adverse events occurred in 101 (67%) of 150 patients in the robotic cystectomy group and 105 (69%) of 152 patients in the open cystectomy group. The most common adverse events were urinary tract infection (53 [35%] in the robotic cystectomy group vs 39 [26%] in the open cystectomy group) and postoperative ileus (33 [22%] in the robotic cystectomy group vs 31 [20%] in the open cystectomy group). In patients with bladder cancer, robotic cystectomy was non-inferior to open cystectomy for 2-year progression-free survival. Increased adoption of robotic surgery in clinical practice should lead to future randomised trials to assess the true value of this surgical approach in patients with other cancer types. National Institutes of Health National Cancer Institute.

Determining the optimal time for radical cystectomy after neoadjuvant chemotherapy.

To determine whether the recovery window (RW) between neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) affects 90-day postoperative morbidity and incidence of lymph node metastasis. We reviewed patients treated with NAC and RC from 1995 to 2013 for ≤cT4 N0 M0 bladder cancer. The association of the RW with 90-day perioperative morbidity and lymph node metastasis was determined. Generalised linear models were used to determine predictors of each endpoint. Patients were stratified into four RWs by 21-day intervals (18-42; 43-63; 64-84; and ≥85 days) from last day of NAC to RC. We evaluated 306 patients with RW information during the study period. The median (range) RW was 46 (18-199) days. There was no difference in overall morbidity, re-admission, or major complication rates amongst the four RWs. In the multivariable analysis extravesical disease was an independent predictor of overall morbidity (odds ratio [OR] 1.95, 95% confidence interval [CI] 1.16-3.26; P = 0.011). Age (OR 1.05, 95% CI: 1.02-1.09; P = 0.004), and surgical duration ≥7 h (OR 2.87, 95% CI: 1.52-5.42; P = 0.001) were independent predictors of major complications. Only surgical duration ≥7 h was a predictor of re-admission (OR 2.24; 95% CI: 1.26-3.98; P = 0.006). A RW of ≥85 days had the highest incidence of node-positive disease (pN+; 40%). In a separate multivariable model that included clinical predictors for pN+, a RW of ≥85 days was an independent predictor of nodal metastasis (OR 2.92, 95% CI: 1.20-7.09; P = 0.018). Patients treated with NAC for bladder cancer can undergo RC between 18 and 84 days (2.5-12 weeks) after NAC with no difference in the risk of perioperative morbidity. Delaying surgery beyond 12 weeks was associated with a significant risk of lymph node metastasis.

Oncologic surveillance following radical cystectomy: an individualized risk-based approach

To provide an alternative surveillance approach for bladder cancer (BC) following radical cystectomy (RC) according to more accurate predictions of a patient's projected BC course. We identified 1797 patients who underwent RC for M0 BC between 1980 and 2007. Patients were stratified by pathologic stage (pT0Nx-0, pTa/CIS/1Nx-0, pT2Nx-0, pT3/4Nx-0, and pTanyN+), relapse location (urethra, upper tract, abdomen/pelvis, chest, and other), age (≤60, 61-70, 71-80, >80years) and Charlson Co-morbidity Index (CCI ≤2 and CCI ≥3). Risks of disease recurrence and non-BC death were modeled using Weibull distributions. Recommended surveillance durations were estimated when the risk of non-BC death exceeded the risk of recurrence. At a median follow-up of 10.6years (IQR 6.8,15.2), 713 patients developed recurrence. Vastly different recurrence patterns were appreciated. Specifically, among patients ≤60years with pT2Nx-0, non-BC death risk exceeded the risk of recurrence in the abdomen at 7.5years following surgery when CCI was ≥3, versus at year 10 after RC when CCI was ≤2. Meanwhile, for patients >80years with pT2Nx-0, non-BC death risk exceeded the risk of abdominal recurrence at 1year after RC, regardless of CCI. We present an alternative post-RC surveillance approach that incorporates a patient's changing risk profile with the influence of competing health factors. We believe this strategy provides more individualized recommendations than current guidelines, and may improve the benefit derived from surveillance while reducing resource misappropriation.

Association of prior pelvic radiation with long-term oncologic outcomes following radical cystectomy.

308 Background: Receipt of pelvic radiotherapy (PRT) prior to radical cystectomy (RC) has unclear association on oncologic outcomes. Methods: The Mayo Clinic Cystectomy Registry was queried to review 2139 patients undergoing RC for M0 bladder cancer between 1990 and 2010. We then identified patients receiving PRT prior to RC, and matched these cases to non-radiated controls (~1:2) on the basis of age, sex, receipt of neoadjuvant chemotherapy, and pathologic T and N stages. Cancer-specific survival (CSS), and progression-free survival (PFS) were estimated using the Kaplan-Meier method and compared with the log-rank test. Results: Of 2139 patients undergoing RC, 104 (4.9%) had received PRT prior to surgery. These patients were matched to 191 non-radiated control patients (no PRT). Overall, patients were well-matched on disease and patient characteristics. Median follow-up was 9.6 years (IQR 6.0, 14.8). During this time, 108 patients experienced disease recurrence and 218 died, including 122 who died from bladder cancer. Five-year CSS among patients who did versus did not receive PRT was 55% versus 63% (p=0.10), while the 5-year PFS was 55% versus 61% (p=0.32). Furthermore, the pattern of disease recurrence (abdominal/visceral, urothelial, local/pelvic, thoracic, soft tissue/other) did not differ between the no PRT and PRT groups (all p&gt;0.05). Conclusions: Receipt of PRT prior to RC is not associated with worse oncologic outcomes. While prior PRT may increase surgical complexity, CSS, PFS, and patterns of recurrence are similar to patients who have not received PRT.

Comparison between standard and reduced volume radiotherapy in bladder preservation trimodality protocol for muscle-invasive bladder cancer patients.

AimOur aim is to compare the toxicity, pelvic nodal relapse, and overall survival of whole bladder irradiation only to the standard technique of whole pelvis irradiation followed by bladder boost in patients with muscle-invasive bladder carcinoma undergoing bladder preservation protocol.Material and methodA total of 60 patients with transitional cell carcinoma, stage T2-3, N0, M0 bladder cancer were subjected to maximal transurethral resection bladder tumour (TURB). Then, the patients were randomised into two groups: group I (30 patients) to receive whole pelvis radiotherapy 44 Gy followed by 20 Gy bladder boost. While group II (30 patients) were randomised to receive whole bladder radiotherapy alone for a total dose of 64 Gy. In both groups, concomitant cisplatin and paclitaxel were given weekly throughout the whole course of radiotherapy where conventional 2 Gy/fraction were used. Additionally, four cycles of adjuvant cisplatin and paclitaxel were given after the end of the chemoradiotherapy induction course.ResultsThe first assessment after the induction chemoradiotherapy showed that complete response was achieved in 73.3% of patients in group I and 76.7% of the patients in group II. After a median follow-up of 2 years, regional relapse occurred in 7.1% of patients in group I and 10.3% in group II. (p = 1). Distant metastases were detected in 17.9% of patient in group I and 13.8% in group II (p = 0.73). The 2-year disease-free survival was 60% in group I and 63.3% in group II (p = 0.79). The whole 2-year overall survival was 75% in group I and 79.3% in group II (p = 0.689). Radiation gastrointestinal (GI) acute toxicity was higher in group I than in group II (p = 0.001), while late GI radiation toxicity was comparable in both groups.ConclusionTreating the bladder only, without elective pelvic nodal irradiation, did not compromise pelvic control rate, but significantly decreased the acute radiation toxicity.