Incidence of Cancer in ANCA-Associated Vasculitis: A Meta-Analysis of Observational Studies

Objective The purpose of this paper is to examine cancer incidence in patients with ANCA-associated vasculitis (AASV) derived from population-based cohort studies by means of meta-analysis. Methods Relevant electronic databases were searched for studies characterizing the associated risk of overall malignancy in patients with AASV. Standardized incidence rates (SIRs) with 95% confidence intervals (CIs) were used to evaluate the strength of association. We tested for publication bias and heterogeneity and stratified for site-specific cancers. Results Six studies (n = 2,578) were eventually identified, of which six provided the SIR for overall malignancy, five reported the SIR for non-melanoma skin cancer (NMSC), four for leukemia, five for bladder cancer, three for lymphoma, three for liver cancer, four for lung cancer, three for kidney cancer, four for prostate cancer, four for colon cancer and four for breast cancer. Overall, the pooled SIR of cancer in AASV patients was 1.74 (95% CI = 1.37-2.21), with moderate heterogeneity among these studies (I-2 = 65.8%, P = 0.012). In sub-analyses for site-specific cancers, NMSC, leukemia and bladder cancer were more frequently observed in patients with AASV with SIR of 5.18 (95% CI = 3.47-7.73), 4.89 (95% CI = 2.93-8.16) and 3.84 (95% CI = 2.72-5.42) respectively. There was no significant increase in the risk of kidney cancer (SIR = 2.12, 95% CI = 0.66-6.85), prostate cancer (SIR = 1.45, 95% CI = 0.87-2.42), colon cancer (SIR = 1.26, 95% CI = 0.70-2.27), and breast cancer (SIR = 0.95, 95% CI = 0.50-1.79). Among these site-specific cancers, only NMSC showed moderate heterogeneity (I-2 = 55.8%, P = 0.06). No publication bias was found by using the Begg's test and Egger's test. Conclusions This meta-analysis shows that AASV patients treatment with cyclophosphamide (CYC) are at increased risk of late-occurring malignancies, particularly of the NMSC, leukemia and bladder cancer. However, there is no significant association between AASV and kidney cancer, prostate cancer, colon cancer and breast cancer. These findings emphasize monitoring and preventative management in AASV patients after cessation of CYC therapy is momentous.