Induction Course Of Bacillus Calmette-Guérin Research Articles

MP54-14 MENTAL HEALTH ILLNESS IN PATIENTS WITH NON-MUSCLE INVASIVE BLADDER CANCER. DOES BCG PLAY A ROLE?

You have accessJournal of UrologyCME1 Apr 2023MP54-14 MENTAL HEALTH ILLNESS IN PATIENTS WITH NON-MUSCLE INVASIVE BLADDER CANCER. DOES BCG PLAY A ROLE? Valentina Grajales, Zhigang Duan, Wei Shen Tan, Roberto Contieri, Hui Zhao, Sharon Giordano, Stephen B. Williams, and Ashish M. Kamat Valentina GrajalesValentina Grajales More articles by this author , Zhigang DuanZhigang Duan More articles by this author , Wei Shen TanWei Shen Tan More articles by this author , Roberto ContieriRoberto Contieri More articles by this author , Hui ZhaoHui Zhao More articles by this author , Sharon GiordanoSharon Giordano More articles by this author , Stephen B. WilliamsStephen B. Williams More articles by this author , and Ashish M. KamatAshish M. Kamat More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003307.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Up to a third of cancer patients experience a mental health condition during their cancer treatment; Bacillus Calmette-Guerin (BCG) has been shown to be neuroprotective. Herein, we assess the incidence of mental health illness (MHI) in non-muscle invasive bladder cancer (NMIBC) patients and the impact of intravesical BCG on the development of non-neurodegenerative MHI. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare data set, we identified 30,991 patients diagnosed with NMIBC between 2005-2017. MHI diagnosis and BCG treatment were identified using ICD9/ICD10 diagnosis codes and HCPCS codes from Medicare inpatient, outpatient, and physician claims. We excluded developmental, organic, and neurodegenerative MHI. Descriptive statistics were done using the Pearson’s chi-square test for categorical variables. RESULTS: A total of 27.0% of patients (N=8,367) received at least an induction course of BCG. Pre-existing MHI was present in 15.9% (N=4,928) of patients 1 year prior to bladder cancer diagnosis. These patients had lower rates of induction BCG (23.0% VS 27.8%, p<0.001). Excluding pre-existing MHI, 43.7% (N=11,377) of patients developed MHI after their bladder cancer diagnosis. Both female and older patients had higher rates of developing MHI (p<0.001), Table 1. Patients without pre-existing MHI treated with at least an induction course of BCG (N=7,233) had a lower MHI development rate than those who did not receive BCG (41.5% VS 44.5%, p<0.001). CONCLUSIONS: Patients with NMIBC are at high risk of developing MHI after diagnosis especially elderly and female patients. Patients who received at least induction BCG treatment had lower rates of developing de novo MHI, however, those with pre-existing MHI were less likely to receive BCG. Source of Funding: This research was supported by the Wayne B. Duddlesten Professorship in Cancer Research © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e759 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Valentina Grajales More articles by this author Zhigang Duan More articles by this author Wei Shen Tan More articles by this author Roberto Contieri More articles by this author Hui Zhao More articles by this author Sharon Giordano More articles by this author Stephen B. Williams More articles by this author Ashish M. Kamat More articles by this author Expand All Advertisement PDF downloadLoading ...

Variation in Statewide Intravesical Treatment Rates for Non-Muscle Invasive Bladder Cancer During the Bacillus Calmette-Guerin Drug Shortage

To measure the changes in treatment patterns for non-muscle invasive bladder cancer before and during the Bacillus Calmette-Guerin (BCG) drug shortage. We used a 5% random sample of Medicare beneficiaries and identified 7971 bladder cancer patients (2648 pre-BCG shortage and 5323 during the shortage) ≥66 years of age who received intravesical treatment within 1 year of diagnosis between 2010 and 2017. The BCG shortage period was defined from July 2012 ongoing. Full induction treatment with BCG, mitomycin C, gemcitabine, or other intravesical agents was defined as receiving ≥5 of 6 treatments within 60 days. State-level BCG use before and during the drug shortage was compared in US states reporting at least 50 patients in each period. Independent variables included year of index date, age, sex, race, rurality, and region of residence. BCG utilization rates decreased 5.9%-33.0% in the shortage period (95% CI (-8.2%)-(-3.7%)). The proportion of patients that completed a full induction course of BCG decreased from 31.0% in the pre-shortage period to 27.6% in the shortage period (P = .002). 84% of reporting states (16 of 19) had decreased BCG utilization ranging between 5% and 36% compared to pre-shortage rates. During the BCG drug shortage, eligible bladder cancer patients were less likely to receive gold standard intravesical BCG with a large variation in treatment patterns between US states.

The association of salvage intravesical therapy following BCG with pathologic outcomes and survival after radical cystectomy for patients with high-grade non-muscle invasive bladder cancer: A multi-institution analysis

IntroductionWhile numerous current clinical trials are testing novel salvage therapies (ST) for patients with recurrent nonmuscle invasive bladder cancer (NMIBC) after bacillus Calmette-Guérin (BCG), the natural history of this disease state has been poorly defined to date. Herein, we evaluated oncologic outcomes in patients previously treated with BCG and ST who subsequently underwent radical cystectomy (RC). MethodsWe identified 378 patients with high-grade NMIBC who received at least one complete induction course of BCG (n = 378) with (n = 62) or without (n = 316) additional ST and who then underwent RC between 2000 and 2018. Oncologic outcomes were compared using the Kaplan-Meier method and Cox proportional hazards models. Sensitivity analyses were conducted stratifying by presenting tumor stage, matched 1:3 for receipt vs. no receipt of ST. ResultsPatients receiving ST were more likely to initially present with CIS (26% vs. 17%) and less likely with T1 disease (34% vs. 50%, P = 0.06) compared to patients not treated with ST. Receipt of ST was not associated with increased risk of adverse pathology (≥pT2 or pN+) at RC (31% vs. 41%, P = 0.14). Likewise, 5-year cancer-specific survival did not significantly differ between groups on univariable Kaplan-Meier analysis (73% for ST and 74% for no ST, P = 0.7). Moreover, on multivariable analysis, receipt of ST was not significantly associated the risk of death from bladder cancer (HR 1.12; 95% CI 0.60–2.09, P = 0.7). Results were unchanged on sensitivity analysis. ConclusionsThese data suggest that, in carefully selected patients, ST following BCG for high grade NMIBC does not compromise oncologic outcomes for patients who ultimately undergo RC.

Robotic cystectomy histopathology outcomes in patients who have ‘failed’ Bacillus Calmette–Guérin: A case series

Objective: Robot-assisted radical cystectomy (RARC) is considered the gold-standard for patients who fail Bacillus Calmette–Guérin (BCG) treatment for high-grade non-muscle-invasive bladder cancer. We reviewed our histopathological outcomes to assess whether we are proceeding to cystectomy at an appropriate time. Methods: A retrospective analysis of the RARC database (2015–2020) was performed to identify patients who received intravesical BCG before cystectomy. Data regarding demographics, number of BCG instillations and staging were collected. Histopathological stage at cystectomy was compared between patients who received an induction course of BCG only (group A), and those who had continued maintenance doses (group B). Results: A total of 73 patients (57 males and 16 females) met the final inclusion criteria, with 24 patients in group A and 49 patients in group B. At cystectomy, 19 patients had ⩾T2 disease (group A: 7; group B: 12). There was no significant difference between groups ( p=0.78). Pelvic lymph node dissection was performed in 68 patients, with six patients found to have lymph node metastases. Conclusion: RARC plays a key role in managing BCG failure, considering the number of patients with muscle-invasive disease at final staging. However, prolonged BCG treatment was not associated with more advanced disease in our case series. Thus, persistence with intravesical treatment warrants consideration for selected patients. Level of evidence: Level 4.

The obesity paradox: defining the impact of body mass index and diabetes mellitus for patients with non-muscle-invasive bladder cancer treated with bacillus Calmette-Guérin.

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

Phase Ib study: APL-1202 (APL) in combination with Bacillus Calmette-Guerin (BCG) in recurrent non-muscle invasive bladder cancer (NMIBC).

e17039 Background: APL is a selective human methionine aminopeptidases II (MetAP2) inhibitor. In preclinical studies, APL has demonstrated both anti-angiogenic and anti-tumor activities as well as a potential synergistic effect with BCG or PD-1. A. This phase 1b study assesses the tolerability and pharmacokinetics (PK) characteristics of oral APL and intravesical BCG combination in HR NMIBC pts. Methods: Pts who had received a prior induction course of BCG within 12 weeks (wks) of enrollment and were scheduled to receive either maintenance or another induction course of BCG were given 750 mg/day APL (2x125 mg tablet, TID) for 12 wks. The tolerability and PK of APL was evaluated one wk prior to first BCG instillation and during combination use with BCG. AEs were evaluated to assess safety and tolerability. Wilcoxon matched-pair signed-rank test was used for PK analysis. Results: Six pts (4M, 2F) with a median age of 72.5 yrs (range 58-81 yrs) were enrolled; 4 pts had grade 3 Ta and 2 pts had Tis. Four and 2 pts received induction and maintenance course of BCG, respectively. Six AEs of grade 1 or 2 were reported by 3 pts, and they were respiratory and head congestion, acid reflux, rash, bronchitis, nausea, and cystitis. None of these AEs were judged to be related to APL. Five pts completed the study and 1 pt dropped out due to a grade 1 cystitis after receiving 4 wks of APL and 2 doses of BCG. The PK results suggested similar PK characteristics (plasma AUCtau, Cmax and t1/2, and urinary excreted faction Ae%). Conclusions: APL was well tolerated when given for 12 wks to NMIBC pts who also received induction or maintenance BCG. Further study of APL in combination with BCG is warranted. Clinical trial information: NCT03672240.

Contemporary oncologic outcomes of second induction course BCG in patients with nonmuscle invasive bladder cancer

PurposeAccording to the 2016 American Urological Association (AUA) guidelines for nonmuscle invasive bladder cancer (NMIBC), clinicians should offer a 2nd intravesical induction course of Bacillus Calmette-Guérin (BCG) to patients with persistent or recurrent Ta or CIS disease after a 1st BCG induction course. However, evidence for a 2nd course is limited, and some patients forego a 2nd induction of BCG in favor of a clinical trial or alternate intravesical therapy. We sought to investigate contemporary oncologic outcomes of a 2nd induction course of BCG in a multi-institutional cohort. Materials and methodsThree hundred fifty-three patients who received full induction BCG for NMIBC since 2001 at 2 institutions were identified. Patients were categorized as receiving primary 6-week induction therapy or subsequent 2nd 6-week induction therapy for patients who recurred or persisted. The baseline differences in demographic and tumor characteristics were compared between the 2 groups, and Kaplan-Meier curves were constructed to assess high-grade recurrence free survival (HgRFS) among both groups. Univariable logistic regression was used to determine factors associated with recurrence after 2nd course BCG ResultsA total of 353 patients received 1st induction BCG (BCG1) and 116 patients received a 2nd induction course (BCG2). Maintenance therapy was given to 117 (33.1%) patients after BCG1 and 43 (37.1%) patients after BCG2. Both cohorts were similar in demographics including age, sex, and race. Pathologic stage before treatment differed as BCG1 patients were more likely to have T1 (40.8% vs. 25%) and less likely to have CIS (13.9% vs. 33.6%) (P < 0.001). Complete response (CR) 3 months after BCG1 was observed in 276 patients (78.2%) and 104 patients (89.7%) after BCG2. Responses remained durable, with 36-month CR of 54.7% in BCG1 and 65.6% in BCG2. Progression to MIBC was identified in 1.4% of BCG1 patients vs. 3.4% in BCG2 patients (P = 0.17). Pathologic stage before BCG2 does not predict progression to MIBC (P = 0.21) after BCG2. The time interval between the 1st and 2nd induction of BCG was not significantly associated with response to 2nd induction BCG (P = 0.47). Maintenance therapy after BCG2 was associated with decreased recurrence after 2nd induction course of BCG. ConclusionA 2nd course of BCG is efficacious with a durable HgRFS, validating the recommendations of the 2016 AUA guidelines.

Bacillus Calmette-Guérin unresponsiveness in non-muscle-invasive bladder cancer patients: what the urologists should know.

Transurethral resection of bladder (TURB) with adjuvant intravesical bacillus Calmette-Guérin (BCG) remains the gold standard therapy for intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC). However, this disease is burdened with a high risk of recurrence or progression. For this reason, we sought to review and summarize the current evidence with a non-systematic Medline/PubMed literature search, regarding optimal treatment in BCG failure patients. Radical cystectomy (RC) should be considered as the preferred option in patients who experience a BCG-failure, especially in case of Ta or T1 high grade recurrence which occurred within 3 months of start-date of induction or in early-intermediate BCG relapsing tumors or in case of recurrence after ≥1 maintenance course with a maintenance exposure ≤6 months. However, in BCG-intolerant patients and in patients unfit or who refuse RC, alternative treatments can be proposed. In particular in BCG intolerant patients a reduction of dwell-time, an increase of length of intervals between the doses, use of anti-inflammatory drugs and antibiotics can be practiced for reducing symptoms. In patients with a low-intermediate grade recurrence for primary intermediate-risk tumor or for CIS disease after a single course of induction, a second induction course of BCG (but not further) can be performed. Intravesical chemotherapeutic agents are considered suboptimal but can be proposed in patients unfit or who refuse RC. On the contrary, combination chemotherapy is not indicated in BCG failure patients. Several ongoing trials are testing with promising prospects the efficacy of cytotoxic agents, immunotherapeutic agents, target therapies, devices and other molecules in BCG-failure patients.

Heat shock proteins 60 and 70 are associated with long-term outcome of T1-stage high-grade urothelial tumors of the bladder treated with intravesical Bacillus Calmette-Guérin immunotherapy

ObjectivesHigh-grade nonmuscle-invasive urothelial tumors of the bladder that fail intravesical Bacillus Calmette-Guérin (BCG) immunotherapy are at the highest risk of progression. Initial evidence links heat shock protein expression levels and outcome of bladder cancer after BCG treatment.We aimed to determine the association between HSP60, 70, and 90 expression levels and long-term outcomes of T1 high-grade (T1HG) urothelial bladder tumors treated with BCG immunotherapy. Materials and MethodsData of 54 consecutive patients with primary T1HG bladder tumors who underwent transurethral resection between 2002 and 2008 and received at least an induction course of BCG were reviewed. Immunohistochemical staining for heat shock protein (HSP)60, 70, and 90 were performed on resected specimens.Study outcomes included disease recurrence and progression. The association between HSP expression levels and outcomes were evaluated with univariable and multivariable Cox proportional hazards models. ResultsDuring a median follow-up of 9.6 years, 25 patients had a disease recurrence and 14 patients a disease progression. Estimated 5-year recurrence and progression-free survival were 59% and 81%, respectively.On multivariable analyses, HSP60 staining >65% was associated with a higher risk for progression (hazard ratio [HR] = 3.96, 95% confidence interval [CI] 1.35–11.58, P = 0.012), and HSP70 staining >5% was associated with a decreased risk for progression (HR = 0.33, 95% CI 0.11–0.98, P = 0.045), and recurrence (HR = 0.29, 95% CI 0.13–0.65, P = 0.003). HSP90 expression was not associated with disease recurrence or progression. Five patients had both a HSP60 staining >65% and a HSP70 staining ≤5% all of whom recurred at a median time of 6 months (interquartile range 3, 16) and 80% of whom progressed at a median time of 26 months (interquartile range 5, 60). ConclusionsHSP60 and 70 cellular expression levels are associated with long-term outcome following BCG treatment of T1HG urothelial bladder tumors. These findings, if further validated, may be used to better stratify the risk of disease recurrence and progression in this group of patients.

The role of single instillation chemotherapy in patients who receive subsequent bacillus Calmette-Guérin: A retrospective single centre study, and systematic review of the literature.

This retrospective study was undertaken to evaluate the combined effect of immediate intravesical chemotherapy and subsequent bacillus Calmette-Guérin (BCG) therapy. The study population consisted of 207 intermediate- or high-risk patients with non-muscle invasive bladder cancer who underwent an induction course of BCG between 1993 and 2007. We introduced single immediate instillation of 50 mg epirubicin for all cases in 2004, and thus earlier cases could be considered as historical controls. The primary endpoint was recurrence-free survival (RFS). For cumulative analysis, we systematically reviewed studies indexed in databases. Including ours, the records of 856 patients from a total of 7 studies, including ours, were finally analyzed. In our cohort, the 5-year RFS in patients who received the combination therapy was 66.2%, compared to 55.2% in the BCG alone group (p = 0.149). Multivariate analysis on tumour recurrence showed that patients with the combination therapy had a hazard ratio (HR) of 0.74 (p = 0.189). A subsequent literature review revealed that RFS rates in the combination groups were higher than those in the corresponding BCG alone groups in 4/7 studies (p = 0.02-0.15), and lower in 1 study (p = 0.51). We identified 5 studies which examined a HR for combination therapy, and performed a cumulative analysis. Adding a single chemo-instillation prior to BCG resulted in a significant reduction in tumour recurrence (summary HR 0.69, p = 0.010). Our analysis suggested that the combination of single chemo-instillation with subsequent BCG therapy exhibited an additive effect against potential tumour recurrence.

The predictive value of GSTT1 polymorphisms in predicting the early response to induction BCG therapy in patients with non–muscle invasive bladder cancer

IntroductionWe evaluated the predictive value of glutathione S transferase mu (GSTM1) and theta (GSTT1) polymorphisms in early response to bacillus Calmette-Guérin (BCG) induction therapy in patients with primary non–muscle invasive bladder cancer. MethodsGSTM1 and GSTT1 polymorphisms were analyzed by multiplex polymerase chain reaction using blood genomic DNA from 135 patients with primary non–muscle invasive bladder cancer who were being treated with a single induction course of BCG. BCG nonresponsiveness (early BCG failure) was defined as a tumor recurrence or progression within 12 months after BCG induction therapy. The predictive value of GST polymorphisms was evaluated by Kaplan-Meier analysis and multivariate logistic regression models. ResultsPatients carrying a GSTT1-positive genotype demonstrated a higher likelihood of early BCG failure regardless of cigarette smoking. After stratification based on the tumor stage and grade, the high-risk group (T1G3) with a GSTT1-positive genotype showed a 14-fold higher risk of early BCG failure compared with those with a GSTT1-null genotype. In a combined analysis of 2 genes, the GSTT1-positive/GSTM1-null genotype had a higher risk of BCG nonresponsiveness compared with the GSTT1-null/GSTM1-null genotype (odds ratio = 4.17, 95% CI: 1.54–11.26). By multivariate logistic regression analysis, the GSTT1-positive genotype was an independent predictor of early BCG failure (odds ratio = 3.67, 95% CI: 1.61–8.38). Kaplan-Meier estimates revealed a significant difference in disease-free survival depending on the GSTT1 genotype (log rank test, P = 0.038). ConclusionsThe results of this study suggest that the GSTT1-positive genotype is an independent predictor of early BCG failure. These results can help determine whether patients would benefit from adjuvant BCG treatment or may require more aggressive alternative therapies.

Assessing treatment response after induction Bacillus Calmette-Guerin for carcinomain situof the urinary bladder: can post-induction random bladder biopsies be avoided?

Patients diagnosed with bladder carcinoma in situ (CIS) and treated with intravesical Bacillus Calmette-Guerin (BCG) often undergo post-induction random bladder biopsies to assess treatment response. We sought to determine the correlation between post-induction urinary cytology/cystoscopy and histopathological findings obtained by random bladder biopsies. Patients who were treated with BCG between 2006 and 2010 for CIS, had surveillance cystoscopy and cytology, and subsequently underwent random bladder biopsies were selected for analysis. Patients with a history of or concomitant urothelial cell carcinoma (UCC) stage T1 or higher were excluded. Cystoscopic finings were characterized as follows: negative - no mucosal erythema, raised lesions or papillary tumours; suspicious - mucosal erythema, but no raised lesions or papillary tumours; and positive - sessile or papillary tumours. The accuracy of cytology in predicting the results of subsequent random bladder biopsies was analysed. Of 21 patients included, surveillance cystoscopy findings were characterized as negative in nine, suspicious in seven and positive in five. Of 16 patients with negative/suspicious cystoscopy, 13 had agreement between cytology and biopsy, nine of whom were negative and four positive. Three of 16 patients had positive cytology, but negative biopsies; on further investigation of these three, one had CIS and two subsequent UCC. In the positive cystoscopy group, four of five patients had agreement between cytology and biopsy, two of whom were negative and two positive. One of the five patients had negative cytology, but a positive biopsy. Our data suggest foregoing random bladder biopsies in patients with negative urine cytology and no evidence of intravesical recurrence on cystoscopy following an induction course of BCG for CIS of the urinary bladder.

The Effect of Fibrin Clot Inhibitors on the Immunomodulatory Efficacy of Bacillus Calmette-Guérin Therapy for Non–muscle-invasive Bladder Cancer

To determine if there is a difference in clinical outcomes among non-muscle-invasive bladder cancer patients taking fibrin clot-inhibiting (FCI) medications (aspirin, clopidogrel, or warfarin) while receiving Bacillus Calmette-Guérin (BCG) therapy compared with their counterparts not taking anticoagulation. Our Investigational Review Board-approved database was queried for patients who received an induction course of BCG from 2001 to 2011. The analysis included 224 patients with a minimum of 3 months of follow-up. Recurrence-free survival (RFS), cystectomy-free survival, overall survival, and disease-specific survival were analyzed using the Kaplan-Meier method stratified by FCI status. Logistic regression was used to predict the initial response rate to BCG and progression by FCI status. Of the 224 patients analyzed, 68, 19, and 23 patients were taking aspirin, clopidogrel and warfarin, respectively, at BCG induction. No specific FCI was associated with differences in cystectomy-free survival, overall survival, disease-specific survival, or the likelihood of progression at recurrence. Neither warfarin nor clopidogrel affected RFS. Patients taking aspirin trended toward increased RFS, although this was not statistically significant (P= .058). Multivariate analysis showed aspirin use was associated with an increased initial response to BCG (odds ratio, 2.41; P= .031) Contrary to the postulated inhibitory molecular effect of FCI on BCG-binding activity, this study did not substantiate a significant impact on BCG efficacy of the concomitant use of these medications during BCG induction. The observation that aspirin use potentiates an increased initial response toBCG may warrant further analysis.

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 ...

A Six-Week Course of Bacillus Calmette-Guérin Prophylaxis Is Insufficient to Prevent Tumor Recurrence in Nonmuscle Invasive Bladder Cancer with Strong-Positive Expression of p53

Objective: To determine the impact of p53 overexpression on tumor recurrence after bacillus Calmette-Guérin (BCG) intravesical therapy in patients with nonmuscle invasive bladder cancer (NMIBC). Methods: Between January 1999 and December 2008, 275 patients who received six BCG intravesical instillations for NMIBC (transitional cell carcinoma) after transurethral resection were assessed for differences in outcomes according to the level of p53 overexpression. A multivariate logistic regression model was applied to assess the predictive capacity of variables for recurrence. Overexpression of p53 was determined using monoclonal p53-DO7 antibody. Results: In 275 subjects, the recurrence rate was higher based on the level of p53 expression (p = 0.019). Based on multivariate analysis, a strong-positive p53 >60% (p = 0.031) and tumor grade (p = 0.015) were significant predictors for recurrence. Patients with a strong-positive p53 >60% had a much lower 5-year biochemical recurrence-free survival rate than patients with p53 ≤60% (72.1 vs. 31.5%, p < 0.001). Conclusions: Strong overexpression of p53 was predictive of recurrence in patients with NMIBC undergoing intravesical BCG treatment. A 6-week induction course of BCG alone is not sufficient to prevent recurrence in patients with NMIBC with high p53 expression; additional prophylactic strategies are needed for these patients.

Intravesical BCG for bladder cancer

Intravesical BCG for bladder cancer

Defining Bacillus Calmette-Guerin Refractory Superficial Bladder Tumors

We define bacillus Calmette-Guerin (BCG) refractory, high risk, superficial bladder cancer. A total of 93 patients received a 6-week induction course of BCG. They were evaluated for response after 3 and 6 months. Half of the patients received monthly maintenance BCG for 2 years and half did not. In both groups the initial responses to BCG at 3 and 6 months were correlated with subsequent tumor recurrence and progression. Of the 93 cases 57% were negative for tumor at 3 months and 43% had residual tumor resected. At 6 months 80% of the patients were tumor-free and 20% had persistent or recurrent tumor. Maintenance BCG did not decrease tumor recurrence further than induction BCG. Subsequent tumor-free interval during 24 months of followup were best predicted by response to BCG after 6 months. A minimum treatment and followup time of 6 months is required to identify high risk, superficial bladder tumors as truly BCG refractory.