What are the possible adverse effects of Bacillus Calmette-Guérin (BCG) immunotherapy for bladder cancer?

Updated: Nov 12, 2019
  • Author: Gary David Steinberg, MD, FACS; Chief Editor: Bradley Fields Schwartz, DO, FACS  more...
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Usually, the first 1-3 instillations of bacillus Calmette-Guérin (BCG) vaccine cause very few adverse effects, unless the patient has been previously vaccinated with BCG vaccine or has a history of tuberculosis. After the third instillation, patients usually begin experiencing irritative bladder symptoms and/or flulike symptoms that last 24-72 hours. These symptoms are usually mild and can be controlled with bladder antispasmodics, NSAIDs, and antihistamines, and they are often perceived as favorable immunological responses to the therapy. Nearly 80% of patients can expect to experience this type of reaction.

In a randomized controlled study of 166 patients, the complete response rate for low dose BCG was 79% compared to 85% for standard dose BCG. However, low dose BCG was associated with significantly less fever and micturition pain and significantly higher quality of life scores. There were no significant differences between the groups in terms of recurrence, progression and overall survival. [8]

A study by Rosevear et al found that a poor response to BCG plus interferon-α therapy in patients with carcinoma in situ were associated with prior tumor stage, 2 or more prior BCG failures, and a BCG failure pattern. [9]

Patients who develop a fever of higher than 39°C (102.2°F) and those who have gross hematuria, severe irritative symptoms lasting more than 72 hours, a urinary tract infection, elevated liver enzyme levels, arthritis, epididymoorchitis, or acute prostatitis should not receive additional BCG vaccine therapy until these findings have resolved. These are symptoms of a systemic BCG reaction, and further administration is unnecessary, immunosuppressive, and potentially lethal. BCG therapy should be administered at reduced doses half or a quarter dose can be administered.

Severe reactions to BCG vaccine, including high-grade fevers (ie, temperature >40°C [104°F]), hepatotoxicity, respiratory distress, chills, hemodynamic instability, and mental status changes, suggest life-threatening septicemia. These are emergencies, and patients should be hospitalized.

A urine culture should be obtained because many cases of septicemia following BCG vaccine instillation are caused by more common uropathogens, rather than the organisms in the BCG vaccine. Tuberculosis organisms from the urine or tissues are usually difficult to culture.

Treatment should be initiated without waiting for culture results. Broad-spectrum antibiotics should be administered intravenously, and the patient should be started on antituberculosis therapy, including rifampin, isoniazid, and cycloserine, which is the only antituberculosis drug to reach bactericidal levels within 24 hours of administration. Corticosteroids are also recommended in some patients.

When BCG vaccine therapy was introduced, several deaths were reported, all of which could be attributed to improper use of this agent. At present, a death is extraordinary because clinicians have learned how to administer this agent and to stop therapy before a patient becomes ill.

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