High-grade Non-muscle Invasive Bladder Cancer Research Articles

Non-Muscle-Invasive Bladder Cancer in the Elderly Patient

With increasing life expectancy, both the incidence and the prevalence of bladder cancer (BC) are steadily rising. As over 70 % of newly diagnosed cases are non-muscle-invasive BC (NMIBC), the management of this entity plays a growing role. Clinical decision-making obviously involves age as an essential variable, but there are no evidence-based recommendations for healthcare professionals that stratify diagnosis, staging or therapy based on age. Data suggest that elderly patients are more frequently diagnosed with high stage and high grade NMIBC, and have worse recurrence and progression rates than younger patients. Moreover, elderly patients face both clinical and institutional barriers to appropriate evidence-based treatment; i.e. they are less likely to undergo re-resections, intravesical instillations and early radical cystectomy. Careful patient selection, and treatment algorithms tailored to the needs and the physiological and physical reserve of the individual patient are particularly important. Interdisciplinary collaborative efforts should focus to provide tailored geriatric care for all elderly patients with NMIBC.

Radical Cystectomy after BCG Immunotherapy for High-Risk Nonmuscle-Invasive Bladder Cancer in Patients with Previous Prostate Radiotherapy

Purpose. Intravesical Bacillus Calmette-Guerin (BCG) immunotherapy is indicated for high-grade nonmuscle-invasive bladder cancer (NMIBC). The efficacy of BCG in patients with a history of previous pelvic radiotherapy (RT) may be diminished. We evaluated the outcomes of radical cystectomy for BCG-treated recurrent bladder cancer in patients with a history of RT for prostate cancer (PC). Methods. A retrospective chart review was performed to identify patients with primary NMIBC. We compared the outcomes of three groups of patients who underwent radical cystectomy for BCG-refractory NMIBC: those with a history of RT for PC, those who previously underwent radical prostatectomy (RP), and a cohort without PC or RT exposure. Results. From 1996 to 2008, 53 patients underwent radical cystectomy for recurrent NMIBC despite BCG. Those with previous pelvic RT were more likely to have a higher pathologic stage and decreased recurrence-free survival compared to the groups without prior RT exposure. Conclusion. Response rates for intravesical BCG therapy may be impaired in those with prior prostate radiotherapy. Patients with a history of RT who undergo radical cystectomy after failed BCG are more likely to be pathologically upstaged and have decreased recurrence-free survival. Earlier consideration of radical cystectomy may be warranted for those with NMIBC who previously received RT for PC.

The natural history of secondary muscle-invasive bladder cancer

BackgroundThe management of patients with high-grade non muscle invasive bladder cancer (NMIBC) brings diagnostic and therapeutic challenges. In the current study, we sought to study the natural history of progression to "secondary" muscle-invasive bladder cancer (MIBC)-cancer that developed during follow up of patients presenting with non-muscle invasive bladder cancer (NMIBC).MethodsBetween 1998 and 2008, 760 patients were treated for bladder cancer. Primary MIBC (>=T2) tumors (present upon presentation) were diagnosed in 114 patients. All patients with high-grade NMIBC were treated with intravesical BCG. Mean follow-up was 44 months.ResultsForty patients (6.1%) developed secondary MIBC after a mean period of 21 months from initial diagnosis of bladder cancer. The 2- and 5-year disease-specific survival rates were better for patients with secondary MIBC (90% and 56% compared to 69% and 42% for patients with primary disease, p=0.03). The Kaplan-Meier curves of the two groups were parallel but displaced by approximately 2 years.ConclusionIn the current series, MIBC progression occurred among initially presenting patients with NMIBC in 6.1%. In most patients, the initial diagnosis of NMIBC is correct and muscle invasion occurs after a mean period of about 2 years. This supports a non-radical approach in patients with high-grade T1, Ta or Tis. Meticulous follow-up with liberal biopsy of any suspicious lesion may provide early diagnosis of invasive disease.

1783 LONG-TERM OUTCOMES OF ELECTRO-MOTIVE DRUG ADMINISTRATION OF MITOMYCIN-C AFTER FAILED INTRAVESICAL BCG IMMUNOTHERAPY IN HIGH RISK, NON-MUSCLE INVASIVE TRANSITIONAL CELL CARCINOMA OF THE BLADDER

You have accessJournal of UrologyBladder Cancer: Superficial (II)1 Apr 20131783 LONG-TERM OUTCOMES OF ELECTRO-MOTIVE DRUG ADMINISTRATION OF MITOMYCIN-C AFTER FAILED INTRAVESICAL BCG IMMUNOTHERAPY IN HIGH RISK, NON-MUSCLE INVASIVE TRANSITIONAL CELL CARCINOMA OF THE BLADDER Ruairidh Crawford, Hannah Wright, Jonathan Borwell, Theresa Parker, Bruce Montgomery, and Neil Barber Ruairidh CrawfordRuairidh Crawford Frimley, United Kingdom More articles by this author , Hannah WrightHannah Wright Frimley, United Kingdom More articles by this author , Jonathan BorwellJonathan Borwell Frimley, United Kingdom More articles by this author , Theresa ParkerTheresa Parker Frimley, United Kingdom More articles by this author , Bruce MontgomeryBruce Montgomery Frimley, United Kingdom More articles by this author , and Neil BarberNeil Barber Frimley, United Kingdom More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2873AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES A recent global shortage of Bacillus Calmette-Guérin (BCG) has forced urologists to consider alternative strategies for treatment of non-muscle invasive bladder cancer (NMIBC). Electro-motive drug administration of Mitomycin-C (EMDA MMC) is one possible alternative but there is little long-term data available. We look at the efficacy and tolerability of EMDA MMC in a select patient group. METHODS Retrospective analysis of patients at a single institution who had received intravesical EMDA MMC since 2006. Indications for this treatment included recurrence or persistence of disease following initial treatment with intravesical BCG or failure to tolerate that treatment for high-risk NMIBC. All patients were considered unacceptably high risk for radical cystectomy. Clinical and operative notes and histology were analyzed to determine tolerability, rates of recurrence and disease progression. RESULTS 26 patients were identified; 20 of these completed the treatment fully. The remaining 6 either did not tolerate treatment or followed up at a different hospital. The average age at time of treatment was 79. There were 21 males and 5 females. With a mean follow-up of 44 months, 14 patients (70%) were found to have disease recurrence within the first 12 months. All were subsequently managed endoscopically. The mean time to disease recurrence was 8.4 months. Disease progression was seen in only 2 patients; one developed new high grade NMIBC and another developed metastatic disease 41 months following treatment. There were no other cases of disease progression. Only 4 patients (15.4%) discontinued their treatment due to skin reactions, intolerable storage type lower urinary tract symptoms or significant haematuria. No patients had systemic reactions to the treatment. CONCLUSIONS EMDA MMC may have an important role in treating patients who have failed BCG therapy for high risk NMIBC and who are too unfit for radical surgery. A 30% complete response rate at a year, with an apparent low risk of progression suggests impressive disease control in the long-term in this poor prognostic group. Tolerability is similar to BCG and of note, there were no systemic reactions. More formal evaluation in the form of a well powered, randomized and probably multi-centred study is needed to fully evaluate the role of EMDA MMC in the treatment of high risk NMIBC, either as an initial treatment or as salvage after BCG, and certainly suggests a potential role whilst BCG availability worldwide remains a problem. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e733 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ruairidh Crawford Frimley, United Kingdom More articles by this author Hannah Wright Frimley, United Kingdom More articles by this author Jonathan Borwell Frimley, United Kingdom More articles by this author Theresa Parker Frimley, United Kingdom More articles by this author Bruce Montgomery Frimley, United Kingdom More articles by this author Neil Barber Frimley, United Kingdom More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

Bacillus Calmette‐Guérin immunotherapy for genitourinary cancer

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The administration of Bacillus Calmette-Guérin (BCG) immunotherapy has become the standard of care for high-grade non-muscle invasive bladder cancer (NMIBC) and carcinoma in-situ (CIS) in terms of prevention of recurrence and progression. While most agree on a 6 week induction cycle, various maintenance schedules (if any at all) have been implemented without a unifying consensus. This review assesses the historical emergence of BCG immunotherapy, beginning with its discovery as a vaccinatin for tuberculosis to its effect on the host immune system and potential therapeutic benefits for various oncologic conditions. The data establishing BCG immunotherapy as the standard of care for high-grade NMIBC and CIS over other bladder instillation modalities is presented in addition to the effect maintenance BCG therapy has on sustaining the immuno-protective effect. Bacillus Calmette-Guérin (BCG) immunotherapy is currently the most effective treatment of non-muscle invasive bladder cancer and one of the most successful applications of immunotherapy to the treatment of cancer. This review summarises the history and development of BCG as a modern cancer treatment, appraises current optimal application of BCG immunotherapy in bladder cancer, discusses promising new therapies closely related to BCG, and briefly explores the possibility that BCG or related treatments may have an application in other urological malignancies. BCG is a nonspecific stimulant to the reticuloendothelial system and induces a local inflammatory response with the infiltration of granulocytes followed by macrophages and lymphocytes, particularly helper T cells. The initial BCG controlled trial showed a statistically significant reduction in tumour recurrence and found the advantage increased with duration of follow-up. Similar results were reported in much higher risk patients in an independent concurrent study. Follow-up suggested that a single 6-week course of intravesical BCG provided long-term protection (up to 10 years) from tumour recurrence and even reduced disease progression. While induction BCG (six weekly instillations) reduced recurrence, progression and mortality at 10 years, this advantage was lost by 15 years, and patients remained at high risk for progression without the use of maintenance BCG. In a meta-analysis by the Cochrane group, induction BCG was found to be markedly superior to mitomycin C in high-risk patients but not in low-risk patients. Additionally, the National Comprehensive Cancer Network guidelines lists the use of intravesical BCG as preferred therapy, citing Category 1 data for high-grade Ta, all T1, and any Tis tumours. Maintenance BCG therapy may be the most important advance in BCG treatment of bladder cancer since the initial introduction. The risk of tumour recurrence and disease progression is life-long in most patients, but the immune stimulation induced by BCG wanes with time. Logarithmic dose reduction of BCG in patients with increasing side-effects will typically prevent escalation of toxicity. Simple dose reduction, appropriate antibiotics, and understanding treatment contraindications have greatly increased the safety of BCG. The 3-week maintenance schedule for 3 years has been evaluated in randomised clinical trials and appears to be the current optimal treatment. With the success achieved in bladder cancer and the relative safety and economy of BCG, consideration should be given to further research for its effectiveness in other genitourinary malignancies.

Multi-institutional analysis of sequential intravesical gemcitabine and mitomycin C chemotherapy for non–muscle invasive bladder cancer

ObjectiveApart from cystectomy, few treatment options exist for the management of bacillus Calmette-Guerin refractory non–muscle invasive bladder cancer (NMIBC). We report a multi-institutional experience with sequential intravesical combination chemotherapy using gemcitabine and mitomycin C (MMC) for NMIBC in the treatment of high-risk patients. MethodsWe performed a retrospective review of patients who received 6 weekly treatments with sequential intravesical gemcitabine (1g) and MMC (40mg) chemotherapy for NMIBC. Gemcitabine was administered first and retained for 90 minutes and then drained. MMC was then administered directly after and retained for an additional 90 minutes. Forty-seven patients received treatment from 3 academic tertiary referral centers between 2000 and 2010. ResultsForty-seven patients (median age 70, range 32–85; 36 males, 11 females) who previously failed a median of 2 intravesical treatments were reviewed. Complete response, 1-year, and 2-year recurrence-free survival rates for all patients were 68%, 48%, and 38%, respectively. Median recurrence-free survival for all patients was 9 months (range 1–80). Fourteen of 47 patients (30%) remained free of recurrence with a median time to follow-up of 26 months (range 6–80mo). Ten patients required cystectomy. ConclusionSequential intravesical combination chemotherapy using gemcitabine and MMC appears to be a useful treatment for patients with high-grade NMIBC as well as those with prior bacillus Calmette-Guerin failure. Further prospective studies are warranted.

Her2 amplification distinguishes a subset of non-muscle-invasive bladder cancers with a high risk of progression

BackgroundSeveral studies have employed immunohistochemistry to detect Her2/neu overexpression in urothelial carcinomas, yielding a tremendous range of positive expression rates. Few studies have examined Her2 status in non-muscle invasive bladder...

A second transurethral resection could be not necessary in all high grade non-muscle-invasive bladder tumors

ObjectivesTo evaluate the rate of residual tumor, understaging and perioperative complications in patients with high grade non-muscle-invasive bladder cancer who underwent second transurethral resection (re-TUR). Materials and methodsA retrospective review of 47 patients with high grade non-muscleinvasive bladder cancer who underwent second TUR from January 2007 to December 2009 at our institution. We evaluated the rate of residual tumor and understaging detected by re-TUR, complications, and the cost of the surgery. ResultsTwenty-two patients underwent second TUR because of the absence of muscle in the initial resection specimen (cTx). We observed residual disease in 8/47 patients (17%) and understaging in 2 cases (4.2%); in only 2 patients understaged, muscularis propria was not present in the sample of initial TUR. The other 20 cTx (90%) were cT0 in the re-TUR. We did not identify any case of cT1 understaged in the re-TUR (≥cT2). Six patients (12.6%) reported complications related with the second TUR (one urethral stricture, two patients required reintervention because of bleeding, one febrile urinary infection and two bladder perforations). ConclusionsOur findings show that the absence of muscle in the initial resection specimen is the only risk factor for understaging. Therefore, we consider re-TUR is mandatory in these cases. On the other hand, when complete TUR has been performed and the muscularis propria is present and tumor free (cTa-T1), we consider that systematic re-TUR is not necessary and only indicated in selected patients, even more if we consider that re-TUR is not exempt from complications.

Role of routine transurethral biopsy and isolated upper tract cytology after intravesical treatment of high‐grade non‐muscle invasive bladder cancer

To investigate whether random bladder, and prostatic urethral biopsies and individual upper tract cytologies (restaging) provide useful clinical information in addition to cystoscopy and bladder cytology in assessing initial intravesical therapy response for high-grade non-muscle invasive bladder cancer. We retrospectively reviewed records of all patients who underwent restaging at our institution after treatment for high-grade non-muscle invasive bladder cancer (Ta, T1 and Tis) between January 2000 and October 2009. A total of 78 patients undergoing 116 consecutive restagings were included. The presence of intravesical cancer at restaging was assessed by cystoscopy, bladder wash cytology and random bladder biopsies, whereas ureteral and prostatic urethral disease was determined using upper tract barbotage cytology and prostatic urethral biopsies. Indication for intravesical treatment was carcinoma in situ in 86, high-grade T1 in 16 and high-grade Ta in 14 cases. A total of 48 patients had primary disease and 68 had recurrence. Overall, 59 of 116 (50.9%) restagings showed positive bladder or prostatic biopsy and/or a positive cytology localized to the upper tract. Of the total number of recurrences, 12.9% (15 of 116) showed a negative cystoscopy and negative bladder cytology, and would have been missed on routine surveillance. A total of 23 of 116 (19.8%) restagings showed evidence of prostatic urethral and or ureteral disease. Roughly 25% of high-grade non-muscle invasive bladder cancer early recurrences after induction intravesical therapy would go unnoticed without the addition of random and directed prostate biopsies, and isolated upper tract cytologies to standard cystoscopy and bladder cytology.

Lenalidomide augments the efficacy of bacillus Calmette-Guerin (BCG) immunotherapy in vivo

ObjectiveIntravesical bacillus Calmette-Guerin (BCG) is the gold standard for high-grade non-muscle-invasive bladder cancer (NMIBC); however, some patients do not respond to initial therapy while others relapse and/or progress. Therefore, combination strategies that can enhance the efficacy and sustainability of BCG are needed. Herein, we explore the efficacy of lenalidomide, a thalidomide derivative with immunomodulatory effects, in combination with BCG, both in vitro and in vivo. Materials and methodsWe explored the outcomes of lenalidomide in combination with BCG in vivo using the MBT-2 cell line implanted in C3H immunocompetent mice. Apoptosis, cell proliferation, and microvessel density were measured by immunohistochemistry. In vitro, we performed Western blotting for cell cycle and apoptosis regulatory proteins and a chromatin condensation assay to evaluate TNF-α and FasL in combination with lenalidomide. ResultsIn the mouse model, combination therapy with BCG and lenalidomide resulted in a statistically significant decrease in tumor size compared with the control group. IHC demonstrated a nonsignificant increase in apoptosis in the combination condition and no effect on cellular proliferation. Microvessel density was decreased in all treated conditions. In vitro, caspase-3 activation and chromatin condensation studies demonstrated increased cell death in the combinations of lenalidomide and TNF-α. ConclusionsThe immunomodulatory molecule lenalidomide augments the response to BCG in an in vivo mouse model. This provides the rationale for studying the combination in patients with high grade NMIBC.

1673 NATURAL HISTORY AND OUTCOME OF PATIENTS WITH HIGH RISK NON-MUSCLE INVASIVE BLADDER CANCER TREATED WITH BACILLE CALMETTE GUÉRIN A CONTEMPORARY UK SERIES

You have accessJournal of UrologyBladder Cancer: Superficial I1 Apr 20121673 NATURAL HISTORY AND OUTCOME OF PATIENTS WITH HIGH RISK NON-MUSCLE INVASIVE BLADDER CANCER TREATED WITH BACILLE CALMETTE GUÉRIN A CONTEMPORARY UK SERIES Thomas Grant, Ian Donaldson, Nourdin Kadi, Stephen Thomas, and Hari Ratan Thomas GrantThomas Grant Nottingham, United Kingdom More articles by this author , Ian DonaldsonIan Donaldson Derby, United Kingdom More articles by this author , Nourdin KadiNourdin Kadi Derby, United Kingdom More articles by this author , Stephen ThomasStephen Thomas Derby, United Kingdom More articles by this author , and Hari RatanHari Ratan Derby, United Kingdom More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1531AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The endoscopic management of high-risk non-muscle invasive bladder cancer (NMIBC) is associated with a very high incidence of recurrence and, more worryingly, progression. This mandates intravesical treatment as per European Association of Urology (EAU) guidelines; 27 bladder instillations over 3 years. Bacillus Calmette-Guérin (BCG) is the mainstay of initial treatment of high risk NMIBC in the UK, and has been shown to reduce recurrence and progression rates. However the treatment is often poorly tolerated. Here we review the tolerability and efficacy of intravesical BCG in a cohort of patients with high-grade NMIBC in a UK teaching hospital. METHODS Between April 2006 and December 2008, 83 patients (mean age 75 years, M:F ratio 4.19) who received a first induction course of BCG for high-risk NMIBC were identified retrospectively. Response to BCG was reviewed by assessing their cystoscopic, histological and clinical outcomes. RESULTS 15 patients out of 83 completed 3 years of BCG maintenance. Of the 68 patients who stopped BCG maintenance prematurely, 17 stopped because of tumour recurrence, 3 because they required radiotherapy and 48 due to intolerance of side effects. Of these 48, 7 patients (14.58%) went on to develop a later recurrence, compared to 2 of the 15 patients (13.33%) who completed 27 instillations. Neither of these 2 recurrences required cystectomy however 3 of the 7 recurrences in patients intolerant to BCG side effects had progressed to a muscle invasive TCC and went on to have radical cystectomy. The overall survival at mean follow-up (of 55 months) was 75.90%. Cause of death was TCC-related in 13.25% of cases. CONCLUSIONS In this contemporary, representative UK series of intravesical BCG in high risk NMIBC, we found that compliance with 3 years of BCG induction and maintenance therapy was poor, and in line with previously published data. Interestingly however, at mean follow up of 55 months, the proportion of patients who stopped BCG due to intolerance of side effects had a similar rate of tumour recurrence to those who completed 27 instillations (14.58% vs 13.33% respectively). This suggests that 27 instillations may not be required for optimum efficacy of BCG in order to reduce recurrence and that regimes with shorter maintenance courses may result in better patient compliance. However in this small series it is impossible to conclude whether progression, perhaps the more important clinical outcome can also be reduced by shorter maintenance courses of BCG. Longer term follow up is of course required. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e676 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Thomas Grant Nottingham, United Kingdom More articles by this author Ian Donaldson Derby, United Kingdom More articles by this author Nourdin Kadi Derby, United Kingdom More articles by this author Stephen Thomas Derby, United Kingdom More articles by this author Hari Ratan Derby, United Kingdom More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Best practice in the treatment of nonmuscle invasive bladder cancer

Bladder carcinoma is the most common malignancy of the urinary tract. Approximately 75-85% of patients with bladder cancer present with a disease that is confined to the mucosa (stage Ta, carcinoma in situ) or submucosa (stage T1). These categories are grouped as nonmuscle invasive bladder cancer (NMIBC). Although the management of NMIBC tumours has significantly improved during the past few years, it remains difficult to predict the heterogeneous outcome of such tumours, especially if high-grade NMIBC is present. Transurethral resection is the initial treatment of choice for NMIBC. However, the high rates of recurrence and significant risk of progression in higher-grade tumours mandate additional therapy with intravesical agents. We discuss the role of various intravesical agents currently in use, including the immunomodulating agent bacillus Calmette-Guérin (BCG) and chemotherapeutic agents. We also discuss the current guidelines and the role of these therapeutic agents in the context of higher-grade Ta and T1 tumours. Beyond the epidemiology, this article focuses on the risk factors, classification and diagnosis, the prediction of recurrence and progression in NMIBC, and the treatments advocated for this invasive disease.

Female Gender and Carcinoma In Situ in the Prostatic Urethra Are Prognostic Factors for Recurrence, Progression, and Disease-Specific Mortality in T1G3 Bladder Cancer Patients Treated With Bacillus Calmette-Guérin

BackgroundControversy exists over the most important prognostic factors in T1 high-grade non–muscle-invasive bladder cancer (NMIBC) patients treated with bacillus Calmette-Guérin (BCG). ObjectiveEvaluate prognostic factors for recurrence, progression, and disease-specific mortality after adjuvant intravesical BCG immunotherapy in patients with T1G3 NMIBC and long-term follow-up. Design, setting, and participantsA single-institution retrospective analysis of 146 patients with primary stage T1G3 NMIBC. InterventionAll patients were treated with complete transurethral resection (TUR) plus multiple bladder biopsies that included the prostatic urethra. No second TUR was done. Patients underwent an induction course of intravesical BCG (Connaught strain, 81mg) without maintenance therapy. MeasurementsThe variables analysed for time to recurrence, progression, and death due to bladder cancer (BCa) were gender, age, tumour multiplicity, diameter, aspect, substaging, concomitant carcinoma in situ (CIS), and CIS in the prostatic urethra. Cox regression models were used to assess the univariate and multivariate prognostic importance of these factors and estimate hazard ratios (HRs). Time-to-event distributions were estimated using cumulative incidence functions. Results and limitationsThe median follow-up was 8.7 yr. Sixty-five patients (44.5%) had recurrence, 25 patients (17.1%) had progression, and 18 patients (12.3%) died because of BCa. Female gender and presence of CIS in the prostatic urethra were associated with an increased risk of recurrence (p=0.0003, HR: 2.53), progression (p=0.001, HR: 3.59), and death due to BCa (p=0.004, HR: 3.53). ConclusionsIn primary T1G3 bladder tumours treated with induction BCG, female gender or having CIS in the prostatic urethra were the only prognostic factors for time to recurrence, progression, and disease-related mortality. It is very important to perform a biopsy of the prostatic urethra in patients with primary high-grade NMIBC as a first step to obtain this prognostic information.

Intravesical bacillus Calmette-Guerin immunotherapy after previous prostate radiotherapy for high-grade non-muscle-invasive bladder cancer

ObjectivesIntravesical bacillus Calmette-Guerin (BCG) immunotherapy is a standard treatment for high-grade non-muscle-invasive bladder cancer (NMIBC). We evaluated outcomes of BCG therapy for NMIBC in patients with a previous history of prostate cancer (CaP) radiotherapy (RT). Materials and methodsA retrospective review of patients with a history of CaP RT who subsequently underwent treatment with intravesical BCG for high-grade NMIBC was performed. Patients were categorized as “BCG success” or “BCG failure” (defined as stage progression or recurrent/persistent disease). We evaluated factors related to the radiotherapy (type, interval to BCG), bladder cancer (clinical stage, immunotherapy type, and course), and patient comorbidities, to identify factors associated with BCG failure. ResultsFrom 1996 to 2008, 26 patients with high-grade NMIBC received intravesical BCG immunotherapy after CaP RT. At a mean follow-up of nearly 5 years, 13 patients (50%) were successfully managed with one or more induction courses of BCG with or without the addition of interferon alpha. Twelve (46%) eventually required cystectomy for disease recurrence or progression, of which half had pathologically advanced disease (≥pT3). Clinical stage was similar between BCG success and failure patients (P = 0.40). Those who failed immunotherapy were more likely to have had a longer interval between RT and BCG induction (5.8 vs. 2.4 years, P = 0.02). ConclusionApproximately 50% of patients with NMIBC who were previously exposed to prostate radiation had a durable response to intravesical BCG. For non-responders, extravesical progression was common.

1740 RETROSPECTIVE STUDY OF DIFFERENT OPTIONS IN THE MANAGEMENT OF NON-MUSCLE INVASIVE BLADDER CANCER T1G3: MAINTENANCE BCG IS HERE TO STAY

You have accessJournal of UrologyBladder Cancer: Superficial1 Apr 20111740 RETROSPECTIVE STUDY OF DIFFERENT OPTIONS IN THE MANAGEMENT OF NON-MUSCLE INVASIVE BLADDER CANCER T1G3: MAINTENANCE BCG IS HERE TO STAY Juan Palou, Eduardo Solsona, J. Angulo, Jesús María Fernández, Miguel Unda, and L.M. Piñeiro Juan PalouJuan Palou Barcelona, Spain More articles by this author , Eduardo SolsonaEduardo Solsona Valencia, Spain More articles by this author , J. AnguloJ. Angulo Madrid, Spain More articles by this author , Jesús María FernándezJesús María Fernández Madrid, Spain More articles by this author , Miguel UndaMiguel Unda Madrid, Spain More articles by this author , and L.M. PiñeiroL.M. Piñeiro Madrid, Spain More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2067AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The management of T1G3 non-muscle invasive bladder cancer (NMIBC) has evolved during the last 20 years but recurrence and progression remain the main concerns. The introduction of intravesical Bacillus Calmette-Guerin (BCG) with different doses and number of doses is still under debate. Good first TUR and Re-TUR has become standart of care in high grade NMIBC in order to improve clinical staging and otucomes by decreasing understaging and residual disease. To evaluate, in a large retrospective series of patients, the differences in recurrence, progression to invasive disease and cancer specific survival according to the different treatments received in the different periods before and after the introduction of BCG. METHODS This is a retrospective analysis of 1039 patients with primary and recurrent stage T1G3 NMIBC including 945 males (mean age of 66.5, b9.8 years, range 21–89). All underwent a complete TUR with multiple bladder biopsies, with muscle present in the specimen. All of them were treated conservatively as follows: 1) no BCG, 2) Re-TUR only, 3) BCG Connaught 27 mgrs induction course, 4) BCG Connaught 81 mgrs induction course, 5) BCG Connaught 81 mgrs induction course + maintenance. There were no differences on the distribution in the groups except that patients with CIS and recurrent tumours were treated more frequently with BCG (p<0.001). We evaluate the time to first recurrence, progression to a higher stage (T2 or greater, or metastatic disease), disease specific mortality. Time to event was estimated with Kaplan Meier and then compared using the logrank test and the multivariate Cox proportional hazards regression model. RESULTS The following results were observed with a median followup of 62±39 months. CONCLUSIONS BCG treatment with maintenance offers the best results in recurrence, progression and disease specific survival in patients with stage T1G3 bladder cancer. Full dose BCG is better than one third dose related to the same parameters. There is an important difference in recurrence rate between the patients treated with or wihout BCG. Full dose BCG treatment reduces progression to invasive disease. Disease specific mortality is better in those patients treated with BCG. Despite being a retrospective study, the large number of patients offers an overview of the impact of the different conservative modalities in patients with T1G3 NMIBC. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e698-e699 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Juan Palou Barcelona, Spain More articles by this author Eduardo Solsona Valencia, Spain More articles by this author J. Angulo Madrid, Spain More articles by this author Jesús María Fernández Madrid, Spain More articles by this author Miguel Unda Madrid, Spain More articles by this author L.M. Piñeiro Madrid, Spain More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Narrow band imaging for detecting residual/recurrent cancerous tissue during second transurethral resection of newly diagnosed non‐muscle‐invasive high‐grade bladder cancer

To determine if narrow-band imaging (NBI) can be used to detect high-grade cancerous lesions missed with the white light at the time of a second transurethral resection (TUR) of high-grade non-muscle-invasive bladder cancer (NMIBC). Consecutive patients with newly diagnosed high-grade NMIBC were enrolled in a prospective observational study. Patients with incomplete resection or absence of muscle tissue in the specimen were excluded. About 1 month after the first TUR, NBI cold-cup biopsies were taken from areas suspicious for urothelial cancer at the end of an extensive white-light second TUR protocol including: (i) resection of the scar of the primary tumour; (ii) resection of any overt or suspected urothelial lesions; and (iii) six random cold-cup biopsies of healthy mucosa. In 2008, 47 consecutive patients were recruited after giving written consent (median age 62 years, range 49-83, 39 men and eight women). Nine patients (19%) had macroscopic or microscopic high-grade NMI urothelial cancer, whereas one was reassessed as having muscle-invasive disease at the white-light second TUR plus the six random biopsies. NBI biopsies were taken in 40 of the 47 patients and detected six more patients with high-grade cancerous tissue (13%). In all 16 of the 47 patients (34%) were found to have residual/recurrent cancer using our extensive protocol of second TUR followed by NBI biopsies. Adding NBI biopsies at the end of an extensive second TUR protocol in patients with newly diagnosed high-grade NMIBC can lead to the identification of patients with otherwise missed high-grade residual/recurrent urothelial carcinoma.

Clinical outcome of high‐grade non‐muscle‐invasive bladder cancer: A long‐term single center experience

To report on the long-term clinical outcome of high-grade (G3) non-muscle-invasive bladder cancer (NMIBC) patients treated at a single institution. A retrospective analysis of 93 patients with NMIBC treated between January 1991 and September 2005 was performed. Patients were divided into three groups on the basis of treatment they received after transurethral resection (TUR) of the bladder. Forty-seven patients received adjuvant intravesical epirubicine after TUR of the bladder (Group 1). Twenty-four patients received intravesical bacillus Calmette-Guérin (BCG) (Group 2). A radical cystectomy (RC) was performed on twenty-two patients (Group 3). Median follow up was 68.7 months. Overall, thirty patients (33%) experienced tumor recurrence. The survival rates of Group 3 were significantly higher than the 71 patients undergoing conservative therapy (Group 1 and 2). There was no statistically significant difference between Group 1 and 2, but treatment failure in patients treated with epirubicine was significantly higher than in those with BCG. Cases without concomitant carcinoma in situ (CIS) showed statistically significantly higher survival rates than those with concomitant CIS. RC provides excellent survival rates in patients with high-grade NMIBC. Adjuvant therapy with BCG after a complete TUR of the bladder may be an effective treatment for high-grade NMIBC. If a conservative treatment is preferred to RC, co-existence of a concomitant CIS should be considered with caution.

EVALUATION OF AN ORTHOTOPIC RAT BLADDER UROTHELIAL CELL CARCINOMA MODEL BY CYSTOSCOPY

OBJECTIVES: To enable preclinical testing of intravesical therapies against non-muscle-invasive bladder cancer (NMIBC) in an orthotopic rat bladder tumour model, augmented by the use of serial cystoscopy for in vivo tumour assessment and follow-up. MATERIALS AND METHODS: Fischer F344 rats had a 16-G transurethral cannula placed. The bladder mucosa was conditioned with an acid rinse, followed by a 1-h instillation of 1.5 x 10(6) AY-27 rat bladder urothelial cell carcinoma (UCC) cells (day 0). Cystoscopy (1 mm) was done on day 0 (control) and at 3, 4, 5, 6, 7, 10, 13 and 17 days. At the scheduled times the rats were killed after cystectomy (four at each time) for histopathological examination of the bladder. RESULTS: Overall, tumour establishment was >80%, with predominantly carcinoma in situ preceding or concomitant with invasive tumour growth. All tumours were formed at 3-5 days, and remained non-muscle-invasive up to 5 days. From 6 days, tumours progressed to muscle-invasive disease in 40% of the rats. Visibility at cystoscopy was excellent and tumours were apparent in >90% of rats from 5 days on, with a specificity and sensitivity of >90%. Cystoscopy could not distinguish NMIBC from muscle-invasive disease. CONCLUSIONS: This is a reliable model of orthotopic rat bladder UCC, with early high-grade NMIBC growth, immediately followed by muscle-invasive growth, i.e. the recommended time to start intravesical therapy would be 5 days after tumour cell inoculation. Tumour growth can easily be monitored by cystoscopy, but cannot be used to distinguish NMIBC from muscle-invasive bladder cancer.

Evaluation of an orthotopic rat bladder urothelial cell carcinoma model by cystoscopy

To enable preclinical testing of intravesical therapies against non-muscle-invasive bladder cancer (NMIBC) in an orthotopic rat bladder tumour model, augmented by the use of serial cystoscopy for in vivo tumour assessment and follow-up. Fischer F344 rats had a 16-G transurethral cannula placed. The bladder mucosa was conditioned with an acid rinse, followed by a 1-h instillation of 1.5 x 10(6) AY-27 rat bladder urothelial cell carcinoma (UCC) cells (day 0). Cystoscopy (1 mm) was done on day 0 (control) and at 3, 4, 5, 6, 7, 10, 13 and 17 days. At the scheduled times the rats were killed after cystectomy (four at each time) for histopathological examination of the bladder. Overall, tumour establishment was >80%, with predominantly carcinoma in situ preceding or concomitant with invasive tumour growth. All tumours were formed at 3-5 days, and remained non-muscle-invasive up to 5 days. From 6 days, tumours progressed to muscle-invasive disease in 40% of the rats. Visibility at cystoscopy was excellent and tumours were apparent in >90% of rats from 5 days on, with a specificity and sensitivity of >90%. Cystoscopy could not distinguish NMIBC from muscle-invasive disease. This is a reliable model of orthotopic rat bladder UCC, with early high-grade NMIBC growth, immediately followed by muscle-invasive growth, i.e. the recommended time to start intravesical therapy would be 5 days after tumour cell inoculation. Tumour growth can easily be monitored by cystoscopy, but cannot be used to distinguish NMIBC from muscle-invasive bladder cancer.