Serious Complications of Intravesical Bacillus Calmette-Guerin Therapy in Patients With Bladder Cancer

Abstract

Side effects and serious complications of intravesical bacillus Calmette-Guérin (BCG) therapy were reviewed in 120 patients with transitional cell carcinoma of the urinary bladder from October, 1983 to June, 1989 at Hirosaki University Hospital. As local side effects, 102 patients (85.0%) had bladder irritability with frequency and/or micturition pain, and 46 patients (38.3%) had hematopyuria. As systemic side effects, fever in 43 patients (35.8%), elevation of serum GOT, GPT in 9 patients (7.5%), and malaise in 3 patients (2.5%) were seen. Serious complications were observed in 7 patients. 4 patients had a severely contracted bladder with decreased compliance less than 50 ml, 2 patients had persistent arthritis and one patient had interstitial pneumonia. In all 4 patients with a contracted bladder partial cystectomy was performed before or after intravesical BCG therapy, and three of them received more than ten times instillation of BCG. It was suggested that contracted bladder most likely occurred after frequent BCG instillations in addition to decreased bladder compliance. Contracted bladder was irreversible in 2 patients. Histopathologically, there was marked fibrosis in the muscular layer of the bladder without tuberculous inflammatory changes. It might depend on the severity of fibrosis in the muscular layer whether contracted bladder was reversible or not. Persistent arthritis was nonspecific inflammation with negative culture results for mycobacteria in the joint fluid in 2 patients. In one patient with interstitial pneumonia, fiberoptic bronchoscopy with transbronchial lung biopsy demonstrated marked fibrosis of alveolar septums and increased lymphocyte count without tuberculous inflammatory changes. The pathogenesis of this complications is considered to be a hypersensitivity reaction to BCG.

Long-term Outcome of a Low-dose Intravesical Bacillus Calmette–Guerin Therapy for Carcinoma In Situ of the Bladder: Results After Six Successive Instillations of 40 mg BCG

“…(colony-forming units)/mg] than other strains (13), indicating that equipotent efficacy can be attained even at half of its standard dose (8). On the other hand, we should pay attention to the frequent occurrence of harmful events related to BCG (6), which urges us to reduce the possible complications. By referring to the previous clinical data obtained by BCG instillation at a standard dose (80 mg), we investigated the treatment outcomes in our patients given a lower dose (40 mg) of BCG, attempting to…”

“…Akaza et al (5) observed bladder irritation symptoms in 69%, fever in 43.7% and macroscopic hematuria in 31%. Infrequent but severe adverse effects have also been reported (6), making it necessary to define the optimal BCG instillation method to improve safety while maintaining its efficacy. Although assessment criteria for adverse effects vary among reports, the incidence of local symptoms in the bladder (bladder irritation symptoms, hematuria and pyuria) in this study turned out to be similar to those in previous studies.…”

“…In Japan, BCG (Tokyo 172 strain) instillation at a dose of 80 mg once weekly for eight consecutive weeks is generally performed (5), but adverse effects related to BCG are major obstacles (6). Many investigations have been conducted using various doses and durations of BCG instillation for improving efficacy and reducing adverse effects (7,8).…”

Successful treatment with low‐dose oral steroids for contracted bladder after intravesical instillation of Bacillus Calmette–Guérin

“…The cause of the contracted bladder after BCG instillation remains unclear. However, it has been suggested that severe inflammatory reactions that persist over the long‐term 5 low bladder capacity after partial cystectomy or frequent TURBT, and many BCG instillations 2 may be possible factors associated with contracted bladder. Nagayama et al 6 .…”

“…Contracted bladder is a rare but severe adverse event after intravesical BCG instillation, with an incidence of 0.2–3.3%. 1 , 2 , 3 Conservative treatment with antituberculosis drugs, steroids, and bladder hydrodistension is the first treatment option for contracted bladder. However, cystectomy can be performed in cases in which conservative treatment achieved no improvement.…”