Table 2.

Management of BCG side effects

Local side effect	Management
Symptoms of cystitis	If symptoms are mild, drugs for relieving bladder irritation (e.g., finapyridine), anticholinergic, and non-steroidal anti-inflammatory are feasible. Continue the instillations when symptoms improve within a few days
	If symptoms persist (> 48 h) or worsen: (1) Postpone the instillation or reduce the dose of BCG (2) Perform a urine culture (3) Start empirical antibiotic treatment (e.g., oral quinolone antibiotics)
	If symptoms persist after antibiotic treatment: (1) Postpone the instillation (2) With positive culture: adjust antibiotic treatment according to sensitivity (3) With negative culture: intravesical instillation therapy with quinolones and anti-inflammatory and analgesic drugs, once daily for 5 d (repeat if necessary)
	If symptoms persist, treat with oral anti-tuberculosis drugs (e.g., isoniazid, rifampicin) and corticosteroids
	If there is no response to the treatment and/or caused severe contracted bladder, perform radical cystectomy when necessary
Haematuria	Perform urine culture to exclude haemorrhagic cystitis, if other symptoms present. Perform the instillation again when the urine is clear
	If haematuria persists, perform cystoscopy to evaluate the presence of bladder tumor
	If macro-hematuria occurs, indwelling catheter and continuous bladder irrigation are recommended, and perform endoscopic hemostasis treatment if necessary
Granulomatous prostatitis	If symptoms present, perform urine culture, suspend the instillation, and give isoniazid and rifampicin orally for three months, plus quinolone antibiotics and cortisol drugs. Asymptomatic patients do not require any treatment
Epididymo-orchitis	Perform urine culture, cease intravesical therapy, administer quinolone antibiotics or anti-tuberculous drugs. If symptoms persist, hormone therapy is feasible. Abscess incision drainage is also feasible when abscess occurs. If the treatments above are not effective, consider orchiectomy when necessary
Urethral stricture	Postpone the instillation, perform spasmolytic treatment. Continue the instillations when symptoms are relieved within a few days, and avoid drugs flowing into urethra during instillations. If the symptoms persist or worsen, urethral dilatation or urethrotomy is feasible
Bladder contracture	Postpone the instillation, use lidocaine for sedation and analgesia, perform bladder enlargement if necessary

Systemic side effect	Management
General malaise/fever	Observation for the patients with mild symptoms which resolve within 48 h
	If symptoms worsen (> 38.5 °C for > 48 h), suspend BCG instillations, perform urine culture for bacteria and acid-fast bacilli, treat the patients with broad-spectrum antibiotics and anti-tuberculosis drugs, and consult with relevant physicians if necessary
BCG sepsis	Strictly follow the contraindications to BCG instillations. BCG should be started at least 2 weeks away after TURBT. When sepsis occurs, stop the BCG treatment immediately, transfer the patients to ICU for treatment, perform urine culture for bacteria and acid-fast bacilli, administer broad-spectrum antibiotics, anti-tuberculosis and hormone drugs. For severe cases without renal failure, consider giving oral cycloserine and strengthening the monitoring of its blood concentration. BCG instillation is no longer recommended after the patient's condition improves
Allergic reactions	(1) Postpone the instillations, or suspend the instillations if symptoms worsen (2) Administer antihistamines and anti-inflammatory agents, and increase the dosage of antibiotics or utilize the anti-tuberculosis drugs, if necessary
Other rare adverse reactions	Most rare adverse reactions are considered to be autoimmune reactions such as arthritis, hepatitis, pneumonia, bone marrow suppression, etc. Non-steroidal anti-inflammatory, cortisol, quinolones or anti-tuberculosis drugs are feasible

BCG Bacillus Calmette–Guérin, TURBT transurethral resection of bladder cancer, ICU Intensive Care Unit