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

<div><p>Objective</p><p>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.</p><p>Methods</p><p>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.</p><p>Results</p><p>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 (I² = 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 (I² = 55.8%, P = 0.06). No publication bias was found by using the Begg’s test and Egger's test.</p><p>Conclusions</p><p>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.</p></div

Characteristics of studies of ANCA-associated vasculitis (AASV) and cancer incidence.

<p>Abbreviations: NR, not reported; SIR, standardized incidence rate; CI,confidence interval; GPA, graulomatosis with polyangiitis; MPA, microscopic polyangiitis; CYC, cyclophosphamide; GC, glucocorticoids.</p><p>Characteristics of studies of ANCA-associated vasculitis (AASV) and cancer incidence.</p

Literature search flow diagram.

<p>Literature search flow diagram.</p

Assessment of study quality.

<p>For cohort studies: 1, representativeness of exposed cohort; 2, selection of the nonexposed cohort; 3, ascertainment of exposure; 4, outcome of interest not present at start; 5a, cohorts comparable on basis of main factor; 5b, cohorts comparable on any additional factor; 6, assessment of outcome with independency; 7, follow-up long enough for outcomes to occur; 8, complete accounting for cohorts or subjects lost to follow-up unlikely to introduce bias.</p><p>Assessment of study quality.</p

Pooled site-specific cancer risks in patients with ANCA-associated vasculitis (AASV).

<p>^a Standardized incidence rate and 95% confidence interval</p><p>^b Percentage of total variation attributable to statistical heterogeneity between studies (25%, low; 50%, moderate; 75%, high)</p><p>^c P value for heterogeneity among studies assessed with Chi-squared based Q test</p><p>^d Colorectal cancer</p><p>^e One of three cannot be merged.</p><p>Pooled site-specific cancer risks in patients with ANCA-associated vasculitis (AASV).</p