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Effect of Intravesical Bacilli Calmette-Guerin Therapy After Second Transurethral Resection in Stage Ta T1 High-Grade Bladder Cancer.

ABSTRACT: Background:To evaluate the efficacy of Bacilli Calmette-Guerin (BCG) induction instillation therapy after second transurethral resection (TUR) in stage Ta T1 high-grade bladder cancer. Methods:We performed a retrospective analysis of 49 consecutive new onset Ta T1 high-grade bladder cancer patients treated with second TUR at our affiliated institutions. Residual cancer rate, intravesical recurrence-free survival (RFS), and risk factors related to RFS were evaluated by univariate and multivariate Cox proportional hazard model analyses. Results:Thirty-one patients received BCG therapy after the second TUR (BCG group), and 18 patients were treated with second TUR alone (no BCG group). There were statistically significant differences in the RFS rates between the two groups, (P = 0.037). BCG therapy was the only factor predictive of intravesical recurrence after second TUR in both univariate and multivariate analyses. After the second TUR, BCG therapy significantly decreased intravesical recurrence in the patients with residual tumors (P = 0.014). However, there was no significant difference in intravesical recurrence in the patients with no residual tumors between the two groups (P = 0.359). Conclusion:BCG therapy after second TUR significantly decreased intravesical recurrence of residual tumors found at the second TUR.

SUBMITTER: Kimura Y

PROVIDER: S-EPMC6584257 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Effect of Intravesical Bacilli Calmette-Guerin Therapy After Second Transurethral Resection in Stage Ta T1 High-Grade Bladder Cancer.

Kimura Yusuke Y Honda Masashi M Morizane Shuichi S Hikita Katsuya K Isoyama Tadahiro T Ono Koji K Koumi Tsutomu T Takahashi Chihiro C Takenaka Atsushi A

Yonago acta medica 20190620 2

<h4>Background</h4>To evaluate the efficacy of Bacilli Calmette-Guerin (BCG) induction instillation therapy after second transurethral resection (TUR) in stage Ta T1 high-grade bladder cancer.<h4>Methods</h4>We performed a retrospective analysis of 49 consecutive new onset Ta T1 high-grade bladder cancer patients treated with second TUR at our affiliated institutions. Residual cancer rate, intravesical recurrence-free survival (RFS), and risk factors related to RFS were evaluated by univariate a ...[more]

PMID: 31320823

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

Project description:ObjectiveSeveral guidelines recommended that second transurethral resection should be performed in patients with diagnosis of high-risk non-muscle-invasive bladder cancer. However, therapeutic benefits of second transurethral resection before bacillus Calmette-Guérin intravesical instillation were conflicting amongst previous studies. We investigated the prognostic impact of second transurethral resection before bacillus Calmette-Guérin instillation in high-risk non-muscle-invasive bladder cancer patients.MethodsThis retrospective study included 3104 non-muscle-invasive bladder cancer patients who received bacillus Calmette-Guérin instillations between 2000 and 2019 at 31 collaborative institutions. Univariate and multivariate Cox proportional hazards models were used to assess the risk factors of intravesical recurrence, disease progression, cancer-specific mortality and overall mortality.ResultsIn the entire population, patients undergoing second transurethral resection (33%, 1026/3104) had a lower risk of intravesical recurrence on univariate analysis (hazard ratio 0.85, 95% confidence interval 0.73-0.98, P = 0.027), although it did not remain significant on multivariate analysis (hazard ratio 0.90, 95% confidence interval 0.76-1.07, P = 0.24). Subgroup analysis revealed that, in pT1 patients (n = 1487), second transurethral resection was significantly correlated with a lower risk of intravesical recurrence on multivariate analysis (hazard ratio 0.80, 95% confidence interval 0.64-1.00, P = 0.048), but lower risks of disease progression (hazard ratio 0.75, 95% confidence interval 0.56-1.00, P = 0.049), cancer-specific mortality (hazard ratio 0.54, 95% confidence interval 0.35-0.85, P = 0.007) and overall mortality (hazard ratio 0.73, 95% confidence interval 0.55-0.97, P = 0.027) on univariate analysis.ConclusionsSecond transurethral resection confers accurate pathological staging and could be used to safely select good candidates for intravesical bacillus Calmette-Guérin instillation. We further confirm that second transurethral resection could confer an oncological benefit in pT1 bladder cancer patients treated by bacillus Calmette-Guérin instillation, and so strongly recommend second transurethral resection in this patient population.

Project description:BackgroundIntravesical Bacillus Calmette-Guerin (BCG) is an effective treatment for bladder superficial carcinoma and it is being tested in interstitial cystitis patients, but its precise mechanism of action remains poorly understood. It is not clear whether BCG induces the release of a unique set of cytokines apart from its pro-inflammatory effects. Therefore, we quantified bladder inflammatory responses and alterations in urinary cytokine protein induced by intravesical BCG and compared the results to non-specific pro-inflammatory stimuli (LPS and TNF-alpha). We went further to determine whether BCG treatment alters cytokine gene expression in the urinary bladder.MethodsC57BL/6 female mice received four weekly instillations of BCG, LPS, or TNF-alpha. Morphometric analyses were conducted in bladders isolated from all groups and urine was collected for multiplex analysis of 18 cytokines. In addition, chromatin immune precipitation combined with real-time polymerase chain reaction assay (CHIP/Q-PCR) was used to test whether intravesical BCG would alter bladder cytokine gene expression.ResultsAcute BCG instillation induced edema which was progressively replaced by an inflammatory infiltrate, composed primarily of neutrophils, in response to weekly administrations. Our morphological analysis suggests that these polymorphonuclear neutrophils are of prime importance for the bladder responses to BCG. Overall, the inflammation induced by BCG was higher than LPS or TNF-alpha treatment but the major difference observed was the unique granuloma formation in response to BCG. Among the cytokines measured, this study highlighted the importance of IL-1beta, IL-2, IL-3, IL-4, IL-6, IL-10, IL-17, GM-CSF, KC, and Rantes as discriminators between generalized inflammation and BCG-specific inflammatory responses. CHIP/Q-PCR indicates that acute BCG instillation induced an up-regulation of IL-17A, IL-17B, and IL-17RA, whereas chronic BCG induced IL-17B, IL-17RA, and IL-17RB.ConclusionTo the best of our knowledge, the present work is the first to report that BCG induces an increase in the IL-17 family genes. In addition, BCG induces a unique type of persisting bladder inflammation different from TNF-alpha, LPS, and, most likely, other classical pro-inflammatory stimuli.

Project description:OBJECTIVES:High-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 METHODS:Data 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. RESULTS:During 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). CONCLUSIONS:HSP60 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.

Project description:Poncet's disease is a rare syndrome characterized by articular impairment in a form of rare tuberculid. One of the theories of its cause involves an autoimmune response induced by the intravesical administration of the Calmette-Guerin Bacillus or the treatment of bladder carcinoma. Furthermore, there may be an appearance of oligoarticular or polyarticular arthritis, beginning 1-3 months after the start of therapy. Few physicians know the disease and the literature related to that syndrome is scarce and restricted to case reports, which contributes to its under diagnosis.Female patient, 64 years old, Caucasian, in whom was noticed firstly dark urine, without haematuria or dysuria. Later felt also colic pain in the hypogastric region. Microscopically, the conclusive diagnosis was a high grade non-invasive papillary urothelial carcinoma. Thereupon, the treatment of the tumour began with transurethral resection technique and intravesical instillation of Calmette-Guérin Bacillus as adjuvant treatment. Eight months after the beginning of treatment, the lingering presence of the carcinoma was identified. Nevertheless, arthritis was identified through radiographs, after an increase in the clavicle capitation, right knee and left ankle in bone scintigraphy. Coinciding with the joint manifestations, the patient developed fever and purulent urethral discharge (culture was negative). Therefore, trying to investigate the cause of the arthritis, Purified Protein Derivate was taken, with reactive results. An increase of acute phase reactants was found, with other tests resulting normal: blood chemistry, Complete Blood Count, immunology and serology. Human Leukocyte Antigen typing by polymerase chain reaction revealed the presence of A24/AX, B44, B27, BW4/BW4, DQ7 and DQ5. Consequently, Poncet's disease was the diagnostic conclusion. The treatment with intravesical Calmette-Guérin Bacillus was immediately discontinued. The patient received corticosteroids associated with etoricoxib and isoniazid for 4 months, achieving disappearance of the inflammatory joint signs in 3 months. After 6 months, no joint pain recurrence or other manifestations suggesting active disease had been seen.Therefore, such diagnosis should be considered when confronted with an osteoarticular clinical picture in patients treated with intravesical Calmette-Guérin Bacillus, especially patients with HLA-B27 (+) and B7 (+), as Poncet's disease is a reactive arthritis.

Dataset Information

Effect of Intravesical Bacilli Calmette-Guerin Therapy After Second Transurethral Resection in Stage Ta T1 High-Grade Bladder Cancer.

Publications

Effect of Intravesical Bacilli Calmette-Guerin Therapy After Second Transurethral Resection in Stage Ta T1 High-Grade Bladder Cancer.

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