Che-Wei Hsu¹, Weiming Cheng^1,4, Hsiao-Yun Hu^2,5, Yu-Hua Fan^3,4, Yi-Chun Chiu^1,4

¹Division of Urology, Department of Surgery, Taipei City Hospital, Zhongxiao Branch, Taipei, Taiwan

²Taipei Databank for Public Health Analysis, Taipei City Hospital, Taipei, Taiwan

³Department of Urology, Taipei Veterans General Hospital, Taipei, Taiwan

⁴Department of Urology, School of Medicine, National Yang-Ming University, Taipei, Taiwan

⁵Institute of Public Health, National Yang-Ming University, Taipei, Taiwan

 

Intravesical Bacillus Calmette-Guerin (BCG) therapy is the treatment of choice for patients with T1 or high grade superficial bladder cancer, or those with carcinoma in situ after transurethral resection. Theoretically, personal history of tuberculosis infection is viewed as a relative contraindication because it will increase the risk of complications or decrease the treatment effectiveness, which hasn’t been supported by any clinical data. Thus, we tried to survey the efficacy and adverse effects of intravesical BCG treatment of bladder urothelial carcinoma in patients with prior tuberculosis infection by analyzing data from National Health Insurance Research Database in Taiwan.

 

From 2000 to 2009, patients who were newly diagnosed with bladder cancer (ICD-9CM 188.0-188.9 and 233.7) by transurethral resection of the bladder tumor (TURBT) and adjuvant intravesical BCG therapy within 3 months were included. Those who developed upper urinary tract cancer (ICD-9CM 189.1 and 189.2) during the studying period were excluded. Disease recurrence, progression, and major adverse effects were compared between those with a prior diagnosis of tuberculosis infection (ICD-9CM 010-018) and those without till December 31^st 2011. Disease recurrence was defined as repeated TURBT after at least 3 times of intravesical BCG therapy. Patients receiving cystectomy or radiotherapy for bladder cancer after at least 3 times of intravescial BCG therapy were viewed as disease progression. Patients with severe urinary tract infection (ICD-9CM 599.0, 038, 590, and 595) who were cared in an intensive care unit were defined as major adverse effect. The times of instillation within 3 months after initiation of the 1^st intravesical therapy were also recruited for analysis. Fisher exact test was used to evaluate the statistical differences of the three outcomes between the two groups, and Wilcoxon rank sum test was used to compare the times of intravesical BCG therapy within 3 months, as well as before the occurrence of disease recurrence and progression.

 

There were 4,763 patients undergoing adjuvant intraveical BCG therapy for bladder cancer from 2000 to 2009. Eight hundred and forty-eight patients had synchronous or metachronous upper urinary tract cancers, and were excluded from analysis. Among the 3,915 patients included for analysis (Table 1), 187 (4.8%) had a diagnosis of prior tuberculosis infection. Compared to patients without prior tuberculosis infection, these patients tended to be male (84.0% versus 76.9%, p = 0.025) and older (p <0.001). There were no statistical differences when it comes to disease recurrence (19.3% versus 20.7%, p = 0.643) or progression (10.2% versus 11.1%, p = 0.811). None of the patients in prior tuberculosis infection group had severe urinary tract infection, while 4 patients (0.1%) developed this major adverse effect after intravesical BCG therapy (p > 0.999). As for keeping up with the instillation schedule, within 3 months after initiation of this adjuvant treatment, patients with prior tuberculosis infection had fewer times of instillation (p = 0.017), but it became insignificant after adjustment for sex and age with Poisson regression test (β=0.113, p = 0.290).

 

From this nationwide population-based study, prior tuberculosis infection does not affect the treatment efficacy or major adverse effect of intravesical BCG treatment for superficial urothelial carcinoma of the urinary bladder. The instillation schedule had no significant difference either. Thus, intravesical BCG therapy is as effective and safe for bladder cancer patients with prior tuberculosis infection as for those without.