BCG infection (BCGitis) following intravesical instillation for bladder cancer and time interval between treatment and presentation: A systematic review

Objective: Intravesical Bacillus Calmette-Guerin (BCG) is an effective treatment in non−−muscle-invasive bladder cancer, however,extravesical BCG infection may occur in remote organs as a potentially serious complication. Researchers aimed to assess whether a differ-ent timing of BCG infection after intravesical administration of BCG could be identified and estimated for each single involved organ.Methods: We performed a systematic literature review over systemic and genitourinary BCG infection case reports, including 271 publishedcase reports for a total of 307 patients. Demographic data, clinical features, and timing of BCG infection development were collected andanalyzed for each patient.Results: BCG infection developed with a different timing from last instillation, depending on the involved organ.Among the genitourinary complications, penile lesions occurred as early as 1 (1;3) weeks, while orchiepididymitis occurred as late as 56(6.25;156) weeks. At the same time, granulomatous hepatitis and lungs involvement such as miliary pulmonary BCG infection occurred ear-lier, with a median time of 1 (1;4) and 1 (1;6) weeks respectively, whereas vascular, osteoarticular, and muscular complications developedwith a median timing from last instillation of 52 (20;104), 68 (14;156), and 93 (29;156) weeks, respectively. The analysis detected a clusterbetween lungs, liver, and bone marrow complications on one side and muscular and osteoarticular or vascular complications on the otherside was also observed.Conclusions: BCG infection after intravesical BCG for bladder cancer may develop even several months or yearsafter the last instillation, depending on the involved organs. When BCG infection interests one or more organ, 2 main associative patternsare common: one involving lungs, liver, and bone marrow, with earlier occurrence but lower rates of microbiological diagnosis achieve-ment, and one involving muscular and osteoarticular or vascular districts, with later occurrence but higher rates of microbiological evidence.