Complications of Bacille Calmette Guerin Therapy

Bacille Calmette-Guérin (BCG) is the most effective intravesical agent available for the treatment of high-risk superficial transitional cell carcinoma (TCC) of the bladder. A live attenuated strain of the bovine tuberculous mycobacterium, BCG exerts its antineoplastic effect through the stimulation of a nonspecific inflammatory reaction at the bladder level. Intravesical treatment is generally safe with fewer than 10 % of patients experiencing complications that require treatment beyond symptomatic palliation (Lamm et al. 1992, Ri-schmann et al. 2000). Side effects can be categorized into local and systemic subtypes. The most common local toxicity is cystitis, with 80% of patients describing varying degrees of irritative voiding symptoms (Resel Folkersma et al. 1999). Low-grade fever (<38.5°C), which occurs in many as one-third of patients soon after intravesical therapy, is the most frequent systemic effect reported (Rischmann et al. 2000). The most serious toxic effects of BCG treatment include BCG-osis, manifested as pulmonary or hepatic infection, and BCG sepsis. Since both present with fever as an early sign, the difficulty lies in differentiating benign, transient fever from that which heralds serious systemic illness. Fortunately, BCG-osis and BCG sepsis each affect less than 1 % of patients (Lamm et al. 1992).

In the setting of serious systemic illness following BCG therapy, suspicion for hematogenous dissemination of mycobacteria or other urinary tract pathogens should be high. Although BCG virulence and host im-munocompetence play a role, trauma to the lower urinary tract is the most common predisposing factor (Lamm et al. 1992). This is reflected in the list of contraindications to intravesical BCG therapy, which include traumatic catheterization and gross or microscopic he-maturia (Table 13.2) (Malkowicz 2002; Lamm et al. 1992). While the literature is sparse, small series have demonstrated no significant morbidity with the use of intravesical BCG in renal transplant patients (Palou et al. 2003). Apart from a lower rate of fever with the Pasteur strain, the relative rates of fever, BCG-osis and

Table 13.2. Contraindications to intravesical BCG therapy

Absolute Relative

Traumatic catheterization Microscopic hematuria Gross hematuria Poor performance status

Immunocompromised Advanced age

Acquired immunodefi- Prior history of tuberculosis ciency syndrome Seropositive human immunodeficiency virus Leukemia Hodgkin's disease Transplant recipients Prior BCG sepsis Prior BCG-osis (pulmonary, hepatic) Intractable urinary tract infection Pregnancy Lactation

13.4 Complications of Bacille Calmette-Guerin Therapy 147

BCG sepsis among the five commercially available strains ofBCG are quite similar (Lamm et al. 1992). Prior febrile responses to BCG therapy and positive skin reactivity to purified protein derivative have both been shown to be predictive of an increased risk of fever and a trend toward an increased risk of systemic side effects (Lamm 1992; Bilen et al. 2003). Interestingly, patients who develop systemic side effects to BCG demonstrate longer disease-free and progression-free survival from an oncologic standpoint (Bilen et al. 2003; Suzuki et al. 2002). This implies that patients who mount an augmented systemic reaction toward BCG may also mount a more effective inflammatory response against the bladder tumor.

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