HDCN Article Review/Hyperlink

Talar-Williams C, Hijazi Y, Walther MM, Linehan WM, Hallahan CV, Lubensky I, et al.

Cyclophosphamide-induced cystitis and bladder cancer in patients with Wegener granulomatosis

Ann Intern Med (Mar) 124:477-484 1996

This study describes the incidence and clinical manifestations of bladder toxicity occurring in 145 patients who received cyclophosphamide for the treatment of Wegener's granulomatosis. More than half experienced nonglomerular hematuria. Seventy percent of those with hematuria who had cystoscopy were found to have cyclophosphamide-induced bladder injury. Seven patients developed a transitional-cell carcinoma of the bladder. Six of the seven patients had a total cumulative cyclophosphamide dose exceeding 100 g with a cumulative duration greater than 2.7 years. All of the patients with bladder cancer had microscopic or gross hematuria. None of the patients without hematuria developed bladder cancer. The estimated incidence of bladder cancer after the first exposure to cyclophosphamide was 5% at 10 years and 16% at 15 years.

Comment: Cyclophosphamide is effective for the treatment of Wegener's granulomatosis. Its metabolite, acrolein, is excreted in the urine and is associated with substantial urinary tract toxicity. Although hemorrhagic cystitis is a well-characterized complication or oral cyclophosphamide therapy, this important study defines the incidence of cyclophosphamide-induced cystitis and its relation to transitional-cell carcinoma. This investigation identifies a subgroup of patients at high risk for the development of bladder cancer. (George R. Aronoff, M.D., FACP, University of Louisville)