Diagnosis Of Muscle-invasive Bladder Cancer Research Articles

Delays in radical cystectomy for muscle-invasive bladder cancer.

Delays from the diagnosis of muscle-invasive bladder cancer (MIBC) to radical cystectomy (RC) longer than 12weeks result in higher mortality and shorter progression-free survival. This study sought to identify factors associated with RC delays and to determine whether delays in care in the current treatment paradigm, which includes neoadjuvant chemotherapy (NAC), affect survival. Subjects with American Joint Committee on Cancer stage II urothelial carcinoma of the bladder who underwent RC from 2004 to 2012 were identified from the linked Surveillance, Epidemiology, and End Results national cancer registry and the Medicare claims database and were stratified into RC groups with or without NAC. Cox multivariable proportional hazard models and multivariable logistic regression models assessed the significance of delays in RC for survival and identified independent characteristics associated with RC delays, respectively. This study identified 1509 patients with MIBC who underwent RC during the study period. In comparison with timely surgery, delays in RC increased overall mortality, regardless of the use of NAC (hazard ratio [HR] without NAC, 1.34; 95% confidence interval [CI], 1.03-1.76; HR after NAC, 1.63; 95% CI, 1.06-2.52). Patients proceeding to RC without NAC had higher odds of delayed care if they lived in a high-poverty neighborhood (odds ratio [OR], 1.37; 95% CI, 1.01-2.08) or nonmetropolitan area (OR, 1.61; 95% CI, 1.01-2.55), were men (OR, 2.22; 95% CI, 1.25-4.00), or required a provider transfer for bladder cancer care (OR, 1.82; 95% CI, 1.10-3.03). Delays in care from the time of either the initial diagnosis or the completion of NAC to RC are associated with worse overall survival among patients with MIBC. Timely surgery is fundamental in the treatment of MIBC, and this necessitates attention to disparities in access to complex surgical care and care coordination.

Delaying Radical Cystectomy After Neoadjuvant Chemotherapy for Muscle-invasive Bladder Cancer is Associated with Adverse Survival Outcomes

BackgroundDelaying radical cystectomy (RC) after a diagnosis of muscle-invasive bladder cancer (MIBC) has been associated with adverse survival. However, data are lacking regarding the impact of RC delay in patients receiving neoadjuvant chemotherapy (NAC). ObjectivesTo assess whether the time from last cycle of NAC to RC (time to cystectomy, TTC) is associated with survival among MIBC patients. Design, setting, and participantsThe study cohort comprised 226 patients treated with NAC and RC between 1999 and 2015 for cT2–T4N0M0 bladder cancer. Outcome measurements and statistical analysisDescriptive statistics were used to test the association between TTC and clinicopathologic variables. Overall mortality (OM) and cancer-specific mortality (CSM) were analyzed via Kaplan-Meier estimation according to TTC. We assessed factors associated with OM and CSM using multivariable Cox regression analyses. Results and limitationsThe median TTC was 7.57wk (interquartile range 5.2–10.8). Patients with a Charlson comorbidity index (CCI) ≥1 had a longer TTC than those with a score of <1 (p=0.027). The group with TTC >10wk had significantly lower OM-free (p=0.003) and CSM-free rates (p<0.001) than the group with TTC ≤10wk. TTC was independently associated with higher risk of OM (p=0.027) and CSM (p=0.004) after accounting for age, gender, pathologic extravesical disease, and nodal status. ConclusionsTTC of >10wk after NAC was associated with adverse survival among patients with MIBC. Patients with a higher CCI were more likely to have prolonged TTC. Patient summaryThe impact of delaying radical cystectomy in patients who have received neoadjuvant chemotherapy (NAC) is unknown. In this study we assessed whether prolonged time to cystectomy (TTC) after NAC affects survival outcomes in patients with muscle-invasive bladder cancer. We found that TTC of >10wk was associated with adverse overall survival and cancer-specific survival, and attempts should be made to shorten TTC after preoperative chemotherapy.

Radical cystectomy: a comparative evaluation of perioperative outcomes in patients with a complicated and uncomplicated postoperative period

The objective: to evaluate the diagnostic capabilities of general clinical and special methods of patient examination in predicting complications after the radical treatment of bladder cancer. Patients and methods. This study is based on retrospective data from 126 patients who underwent open radical cystectomy (RCE), with one in three patients who had complications in postoperative period. All patients were divided into two groups according to the Clavien-Dindo classification to identify the predictors for the development of intra– and postoperative complications. The first group comprised of 82 (65,08%) patients with uncomplicated postoperative period. The second group consisted of 44 (34,92%) patients who developed complications of varying severity and required additional instrumental or surgical correction. Diagnostic possibilities of indicators of general clinical and special methods of examination of patients, available for quantitative registration, in predicting favorable and unfavorable outcomes and perioperative complications of RCE were evaluated. Results. As a result of the comparative statistical analysis, 33 objective quantitative indicators characterizing the history of the disease and the objective status of patients showed no statistically significant differences. The age of the patients in the first group was on average 60,8±12,8 years and 58,2±9,5 years in the second group, р>0,05. This insignificant difference indicates that the elderly age >70 years, in combination with systemic diseases, limit the possibilities and the volume of surgical interventions. As a result the majority of the sampled patients aged 55–60 years. The average period from biopsy and muscle-invasive bladder cancer (MIBC) diagnosis before the RCE was 53,1±42,7 days in the group with uncomplicated postoperative period and 146,9±94,4 days in the group with complications. The indicator in the second group of patients exceeds the limit recommended by the EAU, where this period is limited to 90 days from the time of diagnosis of MIBC and exceeds the terms by 1.6 times. Conclusions. The absence of statistically significant differences between all indicators in both groups indicates the need to create an algorithm to predict the development of postoperative complications for example – mathematical modeling.

Rehabilitation interventions to improve patient-reported outcomes and physical fitness in survivors of muscle invasive bladder cancer: a systematic review protocol

IntroductionSurvivors of muscle invasive bladder cancer (MIBC) experience physical and psychosocial side effects of cancer diagnosis and treatment. These negative side effects have a crucial impact on their health-related quality...

SEOM Clinical Guideline for treatment of muscle-invasive and metastatic urothelial bladder cancer (2016).

The goal of this article is to provide recommendations for the diagnosis and treatment of muscle-invasive and metastatic bladder cancer. The diagnosis of muscle-invasive bladder cancer is made by pathologic evaluation after transurethral resection. Recently, a molecular classification has been proposed. Staging of muscle-invasive bladder cancer must be done by computed tomography scans of the chest, abdomen and pelvis and classified on the basis of UICC system. Radical cystectomy and lymph node dissection are the treatment of choice. In muscle-invasive bladder cancer, neoadjuvant chemotherapy should be recommended in patients with good performance status and no renal function impairment. Although there is insufficient evidence for use of adjuvant chemotherapy, its use must be considered when neoadjuvant therapy had not been administered in high-risk patients. Multimodality bladder-preserving treatment in localized disease is an alternative in selected and compliant patients for whom cystectomy is not considered for clinical or personal reasons. In metastatic disease, the first-line treatment for patients must be based on cisplatin-containing combination. Vinflunine is the only drug approved for use in second line in Europe. Recently, immunotherapy treatment has demonstrated activity in this setting.

Meta-analysis of microRNAs as biomarkers for muscle-invasive bladder cancer.

Bladder cancer is the most common cancer of the urinary tract. A quarter of bladder cancer patients presenting with muscle-invasive bladder cancer (MIBC) suffer significant morbidity and succumb to the disease. MicroRNA (miRNA) from tissue, urine or blood samples of MIBC patients have been demonstrated to differ from healthy individuals, and possibly have diagnostic value. The aim of the present meta-analysis was to access the overall diagnostic accuracy comprehensively and quantitatively. Systematic searching in PubMed, Web of Science, Embase and Chinese National Knowledge Infrastructure database was conducted. The pooled sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR) and diagnostic odds ratio (DOR) were calculated via the random effects model to evaluate the overall test performance. Deeks' funnel plot asymmetry test was used to test the publication bias. A total of 10 studies were included in the meta-analysis, with a total of 577 patients and 412 controls. The pooled sensitivity and specificity were 0.78 [95% confidence interval (CI), 0.69–0.86] and 0.77 (95% CI, 0.72–0.81), respectively. The pooled PLR was 2.9 (95% CI, 2.1–3.8), the NLR was 0.31 (95% CI, 0.27–0.35), the DOR was 7 (95% CI, 4–13) and the pooled AUC was 0.80 (95% CI, 0.69–0.87). In conclusion, the current miRNA assays support their use as markers for MIBC diagnosis.

49 - Radical cystectomy delay of more than 100 days from the diagnosis of muscle-invasive bladder cancer undermines survival among patients under 75 years of age

49 - Radical cystectomy delay of more than 100 days from the diagnosis of muscle-invasive bladder cancer undermines survival among patients under 75 years of age

Preoperative Glasgow prognostic score as a predictor of primary bladder cancer recurrence.

The correlation between systemic inflammatory markers and malignancies has been assessed by a number of recent studies. The aim of this study was to prospectively assess preoperative inflammation markers and Glasgow prognostic scores (GPS) in patients who underwent surgery for primary bladder cancer (BC), and evaluate the predictive value of GPS for disease recurrence and progression. A total of 38 patients (mean age, 60.16±9.71 years; range, 33-76 years) who were treated in our department between May, 2014 and August, 2015 were enrolled in the present study. Preoperatively, patient information regarding gender, body mass index, serum C-reactive protein (CRP) and albumin levels, GPS and comorbidities, were collected and recorded. Transurethral resection of the bladder was performed, followed by histopathological evaluation of the resected material. The tumor size, stage and grade and the presence of necrosis were determined. According to the international TNM classification, the results of the histopathological analysis were as follows: Ta low- (n=24) and high-grade (n=4); and T1 low- (n=2) and high-grade (n=8). The median follow-up period was 10.1 months (range, 6-12 months). During this period, recurrence was observed in 10 cases and disease progression was detected in 1 patient. Hypoalbuminemia was encountered in 40% of the cases with recurrence, which was significantly higher compared with that in patients without recurrence (7.1%; P=0.031). In patients who had recurrence, a GPS of 1-2 points and tumor necrosis were more frequently detected compared with those without recurrence (60 vs. 7.1%, P=0.002; and 80 vs. 7.1%, P=0.001, respectively). Excluding a cystectomized case with a diagnosis of muscle-invasive BC, disease progression was not detected in any of the cases with recurrence during follow-up. Therefore, we consider that GPS and serum markers of systemic inflammatory response may be used as predictors of recurrence in patients with transitional cell BC.

Treatment strategy for bladder cancer in patients on hemodialysis: a clinical review of 28 cases.

To clarify the background, clinical symptoms, pathological characteristics, and duration of survival in patients with bladder cancer on hemodialysis and to examine the appropriate treatment strategies. Between April 1988 and May 2012, 28 patients in whom bladder cancer was diagnosed and treated after dialysis was initiated were included in this retrospective study. We examined the clinicopathological characteristics and survival. Twenty men and 8 women were included (mean age 64.1 ± 11.9 years). The mean duration of dialysis was 80.2 ± 79.1 months. The duration of follow-up after treatment was 43.9 ± 41.2 months. Fourteen patients underwent immediate total cystectomy after the diagnosis of muscle-invasive bladder cancer or high-grade pT1 tumors. Of these, four died of cancer and two had surgery-related deaths. Fourteen patients underwent transurethral resection, and the initial diagnosis was non-muscle-invasive bladder cancer. Of these, three underwent delayed total cystectomy because the time to recurrence was short or there were multiple intravesical recurrences; none died of cancer. The duration of hemodialysis tended to be longer in patients who underwent immediate total cystectomy than in those who underwent only transurethral resection or delayed total cystectomy (107.1 ± 92.0 vs. 53.3 ± 63.9 months, p = 0.10). Bladder cancer in hemodialysis patients can be treated using the same strategy as for the general population. Bladder cancer in longer-term hemodialysis patients tends to be pathologically more advanced; thus, total cystectomy, although highly invasive, is often needed. Establishing bladder cancer screening for patients on dialysis is desirable.

Effect of chemotherapy and/or TURBT on pathologic response in patients receiving neoadjuvant chemotherapy for muscle-invasive bladder cancer.

395 Background: Neoadjuvant chemotherapy (NAC) for muscle−invasive bladder cancer (MIBC) has been associated with a survival benefit in patients who achieve pathologic response. However, a smaller but significant group of patients who receive transurethral resection of bladder tumor (TURBT) without NAC will also be down−staged. We estimated the prevalence of pathologic response to TURBT in patients who receive NAC. Methods: Of 737 serial patients who received radical cystectomy (RC) at Johns Hopkins Medical Center from 2005–2014, 328 with cT2 urothelial carcinoma were identified. 172 patients received NAC and TURBT, while 156 received only TURBT prior to RC. Demographic, clinical, and pathologic information was compared between groups using Wilcoxon−Mann−Whitney for continuous and chi−squared for categorical variables. Pathologic response was defined as &lt; pT2 at RC. A Poisson regression model with robust error variance was used to determine relative risk (RR) of pathologic response in NAC vs. non−NAC patients, adjusting for age, body mass index (BMI), race, gender, Charlson score, smoking status, days from MIBC diagnosis to surgery, and history of prior non−MIBC (NMIBC). Results: Pathologic response was higher in NAC patients compared to non−NAC patients (62% vs. 21%, RR = 3.00). NAC patients were significantly younger than non−NAC patients (64.8 vs. 71.2 years, p &lt; 0.01), with higher BMI (28.1 vs. 26.7 kg/m2, p &lt; 0.01), lower frequency of Charlson score ≥ 3 (13.4% vs. 26.7%, p &lt; 0.01), and lower frequency of prior NMIBC (9.4% vs. 22.4%, p &lt; 0.01). Adjustment resulted in a RR of pathologic response in NAC vs. non−NAC patients of 2.50 (95% CI: 1.69−3.69, p &lt; 0.01). Assuming no interaction between NAC and TURBT, this adjusted model suggests that in a cohort of patients who receive NAC, 40% (95% CI: 27–59%) of pathologic response can be attributed to TURBT. Conclusions: An adjusted model suggests that in a cohort of patients who receive NAC and TURBT prior to RC, 40% of pathologic response can be attributed to TURBT. An understanding of which patients are true responders to chemotherapy and which receive a therapeutic TURBT is needed to select optimal candidates for NAC.

The effect of the time interval between diagnosis of muscle-invasive bladder cancer and radical cystectomy on staging and survival: A Netherlands Cancer Registry analysis

IntroductionData from single-center series suggest that a delay in time to radical cystectomy (RC) more than 3 months after diagnosis of muscle-invasive bladder cancer (MIBC) is associated with pathological upstaging and decreased survival. However, limited data is available from population-based studies. In this study, the effect of delayed RC was assessed in a nationwide cohort. Materials and methodsPatients who underwent RC between 2006 and 2010 with primary clinical T2-T4N0M0 urothelial bladder cancer were selected using the Netherlands Cancer Registry database. Data from the Netherlands Cancer Registry was supplemented with data from the Nationwide Network and Registry of Histo- and Cytopathology database in case of incomplete information. The cohort was divided in patients who underwent RC ≤3 months (group I) vs. patients who underwent RC >3 months (group II). Median time from MIBC diagnosis to RC, variables associated with delayed RC >3 and the effect of delayed RC on staging and overall survival (OS) were evaluated in patients who underwent neoadjuvant therapy and patients who did not. ResultsA total of 1,782 patients were included. Median follow-up time was 5.1 years for living patients and 1.3 years for deceased patients. Median time from MIBC diagnosis to RC was 50 days (interquartile range: 27 days) and 93% of patients underwent RC≤3 months. Patients older than 75 years (odds ratio [OR] = 0.50; 95% CI: 0.32–0.77), referred for RC (OR = 0.41; 95% CI: 0.26–0.69), and treated in a university hospital (OR = 0.34; 95% CI: 0.21–0.56) were less likely to undergo RC≤3 months. Pathologic upstaging rate (43.9% vs. 42.1%) and node-positive disease rate (20.2% vs. 21.7%) did not differ for group I and II. Delayed RC>3 months was not associated with decreased OS adjusting for confounding variables (hazard ratio = 1.16; 95% CI: 0.91–1.48; P = 0.25). Median time from MIBC diagnosis to RC in patients that received neoadjuvant therapy (n = 105) was 133 days (interquartile range: 62 days). Adjusting for confounding variables, delayed RC>3 months was not associated with OS (hazard ratio = 0.90; 95% CI: 0.45–1.82). ConclusionsThe vast majority of patient underwent RC within 3 months after diagnosis of MIBC, as recommended in the European Association of Urology MIBC guideline. Delayed RC for more than 3 months had no adverse effect on staging and survival.

A Retrospective Analysis of the Effect on Survival of Time from Diagnosis to Neoadjuvant Chemotherapy to Cystectomy for Muscle Invasive Bladder Cancer

We determine the impact of the timing of radical cystectomy from the diagnosis of muscle invasive bladder cancer on survival in patients also treated with neoadjuvant chemotherapy. We performed a retrospective chart review of consecutive patients with muscle invasive bladder cancer who received neoadjuvant chemotherapy followed by cystectomy between 1996 and 2014 at a single institution. Cox proportional hazards regression models were used to investigate theeffect of treatment time intervals on overall survival. Three treatment intervals were analyzed for survival impact, from diagnosis of muscle invasive bladder cancer to initiation of neoadjuvant chemotherapy, from initiation of neoadjuvant chemotherapy to cystectomy and from diagnosis to cystectomy. Other pretreatment and posttreatment clinicopathological parameters were also analyzed. Median time from the diagnosis of muscle invasive bladder cancer to radical cystectomy was 28 weeks. Cystectomy performed less than 28 weeks from the diagnosis did not result in significant improvement in overall survival outcomes (HR 0.68, 95% CI 0.28-1.63, p=0.388). Neither the timing of neoadjuvant chemotherapy initiation from diagnosis (median 6 weeks) nor the timing of cystectomy from neoadjuvant chemotherapy initiation (median 22 weeks) was associated with survival. Patient age, variant histology, extravesical and/or lymph node involvement (T3-4 and/or N1 or greater) were significantly associated with survival. The timing of radical cystectomy in relation to muscle invasive bladder cancer diagnosis date does not significantly impact overall survival in patients with muscle invasive bladder cancer receiving neoadjuvant chemotherapy.

Neoadjuvant Radiotherapy Improves Survival in Patients With T2b/T3 Bladder Cancer: A Population-Based Analysis

BackgroundNeoadjuvant radiotherapy (NART) for muscle-invasive bladder cancer (MIBC) is currently underused. However, the outcomes for MIBC have remained suboptimal. We investigated the relationship of NART to cause-specific mortality (CSM) and overall mortality (OM) among patients with a diagnosis of MIBC. Materials and MethodsThe patients diagnosed with primary invasive urothelial carcinoma of the bladder from 1983 to 2008 with localized disease were included. Patients aged > 90 years, those diagnosed with T1 or T4 BC, and those with no information on tumor grade were excluded from the analysis. Kaplan-Meier, Cox regression, and competing risk methods were used in the analysis of OM and CSM. ResultsA total of 5562 patients were included in the cohort (115 NART and 5447 surgery alone). On univariate analysis, NART significantly decreased the OM for patients with high-grade BC (hazard ratio [HR], 0.8), stage T2b (HR, 0.74), and stage T2b/T3 (HR, 0.74). CSM was also lower for those with stage T2b disease (HR, 0.63). Multivariable analysis revealed that NART was associated with a significant decrease in CSM (P = .043) and OM (P = .0462) for those with T2b. Likewise, an improvement was seen in OM (P = .0337) for patients with T2b/T3 who had received NART. ConclusionNART was significantly associated with decreased CSM and OM in patients with clinical T2b/T3 BC and OM for patients with T2b/T3. These data suggest that NART could be beneficial in patients with T2b/T3 BC. In the modern era, the greatest utility would potentially be for patients with an incomplete response to neoadjuvant chemotherapy or as an adjunct to chemotherapy to improve the complete response rates.

A retrospective analysis of the effect of time from diagnosis to cystectomy on survival in patients with muscle-invasive bladder cancer receiving neoadjuvant chemotherapy.

360 Background: Retrospective population-based studies have shown that an interval longer than 12 weeks between diagnosis and cystectomy is associated with worse outcomes in patients with muscle-invasive bladder cancer (MIBC). Neoadjuvant chemotherapy (NAC) is widely used however the impact of duration from diagnosis to cystectomy is unclear in MIBC patients treated with NAC. Methods: We performed a retrospective analysis of patients with MIBC who received NAC followed by cystectomy between 1996 and 2014 at a single institution. Total therapy duration was defined as the time interval between diagnosis of MIBC on biopsy and the date of cystectomy. Cox proportional hazards regression models were used to investigate the effect of total therapy duration and other factors on overall survival (OS). Results: 201 patients who met the study criteria were analyzed.Demographics included: median age 62, 79% male, 62% cT2N0, 10% cN+, 29% w/variant histology (VHx). Cisplatin-based therapy was given to 91% of patients for a median of 3 cycles. The median time from diagnosis to the cystectomy was 28 weeks. A total therapy duration &lt; 28 weeks did not impact OS (hazard ratio [HR], 0.68; p=0.39). Pretreatment clinical covariates associated with improved OS included age&lt; 62 (HR 0.56; p=0.034) and absence of VHx (HR, 0.40, p=0.001). Post-treatment factors of significance included less than 3 cycles of chemotherapy received (HR 1.75, p=0.037), pT3/T4 or N+ (HR 5.18, p&lt;0.001), and N- (HR 0.58, p=0.048). Conclusions: Total therapy duration does not significantly impact OS in patients with MIBC receiving NAC. This data adds to the evidence supporting the use of NAC in MIBC patients fit to receive cisplatin-based regimens.

EORTC Progression Score Identifies Patients at High Risk of Cancer-Specific Mortality After Radical Cystectomy for Secondary Muscle-Invasive Bladder Cancer

BackgroundThe aim of this study was to develop a risk stratification of patients with muscle-invasive bladder cancer (MIBC) after radical cystectomy (RC). For this purpose, we compared the cancer-specific mortality (CSM) of patients with primary MIBC and patients with secondary MIBC in different risk groups according to the European Organisation for Research and Treatment of Cancer (EORTC) progression score. Patients and MethodsThe records of 521 consecutive patients treated with RC for clinical MIBC according to transurethral resection of bladder cancer (TURBT) diagnosis were reviewed. Of the 521 patients, 399 (76.6%) had primary MIBC (study group 1 [SG1]) and 122 (23.4%) had secondary MIBC (study group 2 [SG2]). Patients in SG2 were stratified into risk groups according to the results of the first and last TURBT in non-MIBC using the EORTC progression score. ResultsCSM for patients with primary and secondary MIBC did not differ significantly. Patients in SG2 with the highest risk for tumor stage progression at time of the first and last TURBT in non-MIBC showed a significantly higher CSM after RC compared with patients with low-to-intermediate risk and compared with patients in SG1. In multivariable analyses, stage pT 3/4 (hazard ratio [HR], 2.12; P < .001), lymphovascular invasion (LVI) (HR, 3.47; P < .001), female sex (HR, 1.35; P = .048), and time from diagnosis of MIBC to RC > 90 days (HR, 2.07; P < .001) were significantly associated with higher CSM. ConclusionRisk stratification by the EORTC progression score can help to identify those patients with the highest risk of CSM after progression to MIBC and thus enable us to offer these patients a multimodal treatment. Our results need to be verified in large prospective studies.

529 NEOADJUVANT GEMCITABINE PLUS CARBOPLATIN FOLLOWED BY IMMEDIATE RADICAL CYSTECTOMY IN PATIENTS WITH MUSCLE-INVASIVE BLADDER CANCER: A PROPENSITY SCORE ANALYSIS

You have accessJournal of UrologyUrothelial Cancer: Medical & Surgical Therapy1 Apr 2012529 NEOADJUVANT GEMCITABINE PLUS CARBOPLATIN FOLLOWED BY IMMEDIATE RADICAL CYSTECTOMY IN PATIENTS WITH MUSCLE-INVASIVE BLADDER CANCER: A PROPENSITY SCORE ANALYSIS Takuya Koie, Akiko Okamoto, Hayato Yamamoto, Yuki Tobisawa, Tohru Yoneyama, Kazuyuki Mori, Shingo Hatakeyama, Takahiro Yoneyama, Yasuhiro Hashimoto, Noritaka Kamimura, and Chikara Ohyama Takuya KoieTakuya Koie Hirosaki, Japan More articles by this author , Akiko OkamotoAkiko Okamoto Hirosaki, Japan More articles by this author , Hayato YamamotoHayato Yamamoto Hirosaki, Japan More articles by this author , Yuki TobisawaYuki Tobisawa Hirosaki, Japan More articles by this author , Tohru YoneyamaTohru Yoneyama Hirosaki, Japan More articles by this author , Kazuyuki MoriKazuyuki Mori Hirosaki, Japan More articles by this author , Shingo HatakeyamaShingo Hatakeyama Hirosaki, Japan More articles by this author , Takahiro YoneyamaTakahiro Yoneyama Hirosaki, Japan More articles by this author , Yasuhiro HashimotoYasuhiro Hashimoto Hirosaki, Japan More articles by this author , Noritaka KamimuraNoritaka Kamimura Hirosaki, Japan More articles by this author , and Chikara OhyamaChikara Ohyama Hirosaki, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.602AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Standard neoadjuvant chemotherapy has not yet been established for patients with muscle-invasive bladder cancer. Our pervious phase II trial demonstrated the efficacy and safety of neoadjuvant gemcitabine plus carboplatin (GCarb) chemotherapy followed by immediate cystectomy in patients with muscle-invasive bladder cancer. In the present study, we conducted a propensity score analysis to elucidate clinical significance of the present treatment protocol. METHODS The cohort of neoadjuvant group consists of 120 patients with muscle-invasive bladder cancer. They received 2 courses of GCarb therapy consisting of 800 mg/m2 gemcitabine on days 1, 8, and 15 and carboplatin with an AUC of 4 on day 2 between March 2005 and June 2011. After the chemotherapy, radical cystectomy (RC) and bilateral pelvic lymph node dissection (PLND) were performed at an interval of 1 month. The cohort of RC alone group includes 155 patients with muscle-invasive bladder cancer treated with RC and bilateral PLND between May 1994 and December 2004. Propensity score matching was used to adjust for potential selection biases associated with treatment type. The endpoints were Overall (OS) and disease-free survival (DFS). RESULTS Of the 120 patients who received GCarb and RC, 28 (23.3%) RC specimens showed pT0. The mean interval from the time of diagnosis of muscle-invasive bladder cancer to RC was 61 days. Grade 3/4 neutropenia occurred in 40 patients (33.9%) and thrombocytopenia in 23 patients (19.8%). Propensity score-matched analysis indicated 112 matched pairs from both groups. The median follow-up period was 35.9 months. The 5-year OS rate was 91.5% for neoadjuvant GCarb versus 51.3% for RC alone group (P < 0.0001). The DFS rate was 83.8% for neoadjuvant GCarb versus 53.1% for RC alone (P < 0.0001). Multivariate analysis revealed that the neoadjuvant GCarb regimen was an extremely strong predictor of the improvement in OS and DFS. CONCLUSIONS Although the present study is not randomized, neoadjuvant gemcitabine plus carboplatin therapy followed by immediate RC achieved significantly longer OS and DFS comparing to surgery alone. The clinical usefulness of the present treatment for the patient with muscle-invasive bladder cancer should be verified by further trials. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e217-e218 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Takuya Koie Hirosaki, Japan More articles by this author Akiko Okamoto Hirosaki, Japan More articles by this author Hayato Yamamoto Hirosaki, Japan More articles by this author Yuki Tobisawa Hirosaki, Japan More articles by this author Tohru Yoneyama Hirosaki, Japan More articles by this author Kazuyuki Mori Hirosaki, Japan More articles by this author Shingo Hatakeyama Hirosaki, Japan More articles by this author Takahiro Yoneyama Hirosaki, Japan More articles by this author Yasuhiro Hashimoto Hirosaki, Japan More articles by this author Noritaka Kamimura Hirosaki, Japan More articles by this author Chikara Ohyama Hirosaki, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Gender-dependent cancer-specific survival following radical cystectomy

To assess the impact of detailed clinical and histopathological criteria on gender-dependent cancer-specific survival (CSS) in a large consecutive series of patients following radical cystectomy (RCE) for muscle-invasive bladder cancer (MIBC). Between 1992 and 2007, 388 men and 133 women (25.5%) underwent RCE for MIBC. A prospectively maintained database was analysed retrospectively. Uni- and multivariable Cox-regression analyses calculated the impact of detailed clinical and histopathological criteria on CSS. Median follow-up was 59 months (2-162). Among clinical and histopathological parameters, only type of urinary diversion differed between men and women. In univariable analysis, CSS did not differ between genders. In multivariable Cox-regression analysis, advanced pT-stage (HR = 2.12; P < 0.001), lymphovascular invasion (LVI) (HR = 3.47; P < 0.001), time interval between diagnosis of MIBC and RCE exceeding 90 days (HR = 2.07; P < 0.001) and female gender (HR = 1.35; P = 0.048) were related to reduced CSS. In separate multivariable Cox-models for time period of surgery between 1992 an 1999 (HR = 1.52; P = 0.050), age ≤55 years (HR = 3.00; P = 0.022), presence of LVI (HR = 1.45; P = 0.031) and female gender were associated with independent reduced CSS. Established clinical and histopathological parameters do not differ significantly between both genders in the present series. Reduced CSS in women is present in historic cohorts possibly suggesting improvement in management over the last years. In particular, female gender has a significant negative impact on CSS in patients younger of age and with positive LVI status possibly suggesting different clinical phenotypes.

Efficient delivery of radical cystectomy after neoadjuvant chemotherapy for muscle‐invasive bladder cancer

Cystectomy delay >90 days after a diagnosis of muscle-invasive bladder cancer (MIBC) adversely affects pathologic stage and survival outcomes in patients who undergo primary surgery. After neoadjuvant chemotherapy (NAC), the impact of the timing of cystectomy delivery on these outcomes is uncertain. Poor communication between urologic and medical oncologists can result in cystectomy delay after systemic treatment. The authors of this report hypothesized that a delay in cystectomy delivery after NAC is associated with adverse survival outcomes. An eligible cohort of 153 patients with MIBC received NAC and underwent radical cystectomy between 1990 and 2007. At the authors' institution, the genitourinary team strives to schedule patients for surgery at the time of initial evaluation or after their first chemotherapy cycle. Clinicopathologic characteristics, including timing of cystectomy, chemotherapy delivery, vital status, and reasons for excessive surgical delay, were analyzed retrospectively using an institutional database. A Cox proportional regression model was used to test the association between the timing of cystectomy delivery and survival. The median follow-up for all patients was 3.6 years. The median time to cystectomy was 16.6 weeks and 6.9 weeks from the first and last day of NAC, respectively. In multivariate analyses, the timing of cystectomy delivery from the termination of NAC did not significantly alter the risk of survival. The most common reason for cystectomy delivery beyond 10 weeks (28 patients; 18%) was procedural scheduling. Cystectomy delivery within 10 weeks after NAC did not compromise patient survival and, thus, provided a reasonable window for patient recovery and surgical intervention.

Early outcomes with neoadjuvant high-dose intensity methotrexate, vinblastine, doxorubicin, and cisplatin (HD-MVAC) or gemcitabine and cisplatin (GC) in muscle-invasive urothelial carcinoma of the bladder: A single-institution experience.

280 Background: Compared to MVAC, HD-MVAC achieves significantly higher complete response rates in patients (pts) with metastatic bladder cancer. Based on current literature, 7%-38% of pts with muscle-invasive bladder cancer achieve pathological down-staging (pT0) with neoadjuvant chemotherapy (NC), which correlates with improved disease-free and overall survival. The role of HD-MVAC has not been evaluated in the neoadjuvant setting. In this retrospective study, we present our data in pts who received NC with HD-MVAC or GC followed by radical cystectomy (RC). Methods: From July 2008 to August 2010, 38 (pts) received 4 cycles of NC with either HD-MVAC or GC for at least T2 bladder cancer followed by RC. The endpoints of interest of this study were the complete pathologic response (pT0) or down-staging to &lt; pT2 (pT0, pTis, and pT1) at RC; and median interval to RC from the time of diagnosis of muscle-invasive bladder cancer and start of NC. Results: Median age at the time of diagnosis was 66 years (35-80 years). Fifteen pts received neoadjuvant HD-MVAC, and 23 received neoadjuvant GC. Clinical T stage at the time of diagnosis was T2 in 29 (76%), T3 in 3 (8%), and T4 in 6 (16%) pts. Down-staging to &lt; pT2 was achieved in 8 (53%) of HD-MVAC pts and 10 (43%) of GC pts. pT0 was achieved in 5 (33%) of HD-MVAC pts and 9 (39%) of GC pts. The median interval from time of diagnosis to RC was 129 days (range 84-154) for the HD-MVAC pts, and 145 days (range 108-252) for the GC pts. The median interval from initiation of NC to RC was 85 days (range 53-122) for the HD-MVAC pts and 107 days (range 60-126) for the GC pts. Overall, NC was well tolerated with 80% of HD-MVAC pts and 78% of GC pts completing the planned chemotherapy. To this date, none of the pT0 pts had recurrence. Conclusions: Both neoadjuvant HD-MVAC and GC appear to be well tolerated, with very promising rate of pathological down-staging. Longer follow-up is needed for the survival outcomes of these patients. A shorter interval from diagnosis and initiation of NC to RC might be responsible for our better outcomes comparing to some historical data. No significant financial relationships to disclose.

Actualización de las Guías Clínicas de la Asociación Europea de Urología sobre el carcinoma vesical músculo-invasivo y metastásico

ContextNew data regarding diagnosis and treatment of muscle-invasive and metastatic bladder cancer (MiM-BC) has emerged and led to an update of the European Association of Urology (EAU) guidelines for MiM-BC. ObjectiveTo review the new EAU guidelines for MiM-BC. Evidence acquisitionA comprehensive workup of the literature obtained from Medline, the Cochrane central register of systematic reviews, and reference lists in publications and review articles was developed and screened by a group of urologists, oncologists, and radiologist appointed by the EAU Guideline Committee. Previous recommendations based on the older literature on this subject were taken into account.Levels of evidence and grade of guideline recommendations were added, modified from the Oxford Centre for Evidence-based Medicine Levels of Evidence. Evidence synthesisThe diagnosis of muscle-invasive bladder cancer (BCa) is made by transurethral resection (TUR) and following histopathologic evaluation. Patients with confirmed muscle-invasive BCa should be staged by computed tomography (CT) scans of the chest, abdomen, and pelvis, if available. Adjuvant chemotherapy is currently only advised within clinical trials. Radical cystectomy (RC) is the treatment of choice for both sexes, and lymph node dissection should be an integral part of cystectomy. An orthotopic bladder substitute should be offered to both male and female patients lacking any contraindications, such as no tumour at the level of urethral dissection. Multimodality bladder-preserving treatment in localised disease is currently regarded only as an alternative in selected, well-informed, and compliant patients for whom cystectomy is not considered for clinical or personal reasons. An appropriate schedule for disease monitoring should be based on: a) natural timing of recurrence; b) probability of disease recurrence; c) functional deterioration at particular sites; and d) consideration of treatment of a recurrence. In metastatic disease, the first-line treatment for patients fit enough to sustain cisplatin is cisplatin-containing combination chemotherapy. Presently, there is no standard second-line chemotherapy. ConclusionsThese EAUguidelines are a short, comprehensive overview of the updated guidelines of (MiM-BC) as recently published in the EAU guidelines and also available in the National Guideline Clearinghouse.