Urinary bladder cancer in Wegener's granulomatosis: is it more than cyclophosphamide?

I n this issue of the Annals Knight and coworkers from Sweden report some interesting data on the incidence of urinary bladder cancer in patients with Wegener’s granulomatosis (WG) which, in contrast with previous reports from single or multicentre cohorts, are derived from a population based, nationwide inpatient register. The data of that study confirm the increased risk of bladder cancer in patients with WG after exposure to cyclophosphamide, but the results also indicate that there might be an increased risk for bladder cancer even before the onset of WG. Within a cohort of 1065 patients with WG eight patients had a diagnosis of bladder cancer before WG was diagnosed. Although not statistically significant, the increased incidence of bladder cancer seen before the onset of WG resulted in a relative risk of 2.1 (95% confidence interval (CI) 0.6 to 3.6) compared with the expected prevalence of bladder cancer in Sweden. These epidemiological data confirm an earlier report from our group from 1999, showing a relation of WG to tumours of the urinary tract for the first time in 1999. In that study we reported a significantly higher incidence of renal cell carcinoma in a single centre cohort of 477 patients with WG, resulting in an odds ratio of 8.73 (95% CI 0.92 to 3.48; p,0.05). Interestingly, five out of seven patients developed WG and renal cell carcinoma simultaneously, whereas this temporal association was not found in any of the control patients with renal cell carcinoma and rheumatoid arthritis. This temporal association of the incidence of cancer and onset of WG is now confirmed by the study of Knight and coworkers. In the majority of their patients WG was diagnosed a relatively short time (median 1.5 years) after the onset of bladder cancer, which suggests that both events were somehow, if not causally, related. The odds ratio for simultaneous occurrence of cancer (all types) was 18 for patients with WG compared with control patients, whereas in a cohort of patients with different systemic vasculitides, a concurrence of solid tumours and vasculitis was found in 16 of 23 cases reviewed. Although the overall risk of developing malignant neoplasms in the Swedish cohort (OR 2.0, 95% CI 1.7 to 2.5) and the German cohort (OR 1.79, 95% CI 0.92 to 3.48) was only modestly increased, patients with WG appear to be at an increased risk for certain other tumour subtypes. Beside renal cell and bladder carcinoma increased relative risks for squamous cell skin cancer (OR 7.3, 95% CI 4.4 to 12.0), leukaemias (OR 5.7, 95% CI 2.3 to 12), and malignant lymphomas (OR 4.2, 95% CI 4.2 to 8.3) have been reported.