Epidemiology of Cancer in Systemic Sclerosis—Systematic Review and Meta-Analysis of Cancer Incidence, Predictors and Mortality*

Abstract

Objectives: The study was conducted to improve our understanding of the epidemiology of cancer in systemic sclerosis (SSc) by evaluating the incidence, prevalence, relative risk of overall and site-specific malignancies, predictors and cancer-attributable mortality. Methods: MEDLINE, CINAHL, EMBASE and Cochrane Library (inception-May 2012) were searched. Estimates were combined using a random effects model. Consistency was evaluated using the I 2 statistic. Results: 4876 citations were searched to identify 60 articles. The average incidence of malignancy in SSc was 14 cases/1000 person-years; the prevalence ranged between 4%-22%. Cancer was the leading cause of non-SSc related deaths with a mean of 38%. Overall SIR for all-site malignancy risk was 1.85 (95%CI 1.52, 2.25; I 2 76%). There was a greater risk of lung (SIR 4.69, 95%CI 2.84, 7.75; I 2 93%) and haematological (SIR 2.58, CI 95% 1.75, 3.81; I 2 0%) malignancies, including non-Hodgkin's lymphoma (SIR 2.55, 95%CI 1.40, 4.67; I 2 0%). SSc patients were at a higher risk of leukemia (SIR 2.79, 95%CI 1.22, 6.37; I 2 0%), malignant melanoma (SIR 2.92, 95%CI 1.76, 4.83; I 2 35%), liver (SIR 4.75, 95%CI 3.09, 7.31; I 2 0%), cervical (SIR 2.28, 95%CI 1.26, 4.09; I 2 54%) and oropharyngeal (SIR 5.0, 95%CI 2.18, 11.47; I 2 58%) cancers. Risk factors include a-RNAP I/III seropositivity, male sex, and late onset SSc. Smoking and longstanding interstitial lung disease increase the risk of lung cancer; Barrett's esophagus and a positive family history of breast cancer, respectively, increase the risk of esophageal adenocarcinoma and breast cancer. Conclusions: SSc patients have a twofold increase in all-site malignancy, and greater risk of lung and haematological malignancies that contribute significantly to mortality. Vigilance should be considered in SSc patients with risk factors for cancer.

Incidence, Risk Factors, and Outcomes of Cancer in Systemic Sclerosis

“…This large, well‐characterized study investigated the epidemiology and determinants of cancer in patients with SSc prospectively enrolled in an SSc cohort database linked to Australian cancer registry databases. In our cohort of 1,727 patients with SSc, the cancer incidence and prevalence of 1.3% and 14.2%, respectively, is consistent with previously reported incidence (1.4%) and prevalence (4–22%) (4). Patients with SSc have an increased risk of cancer compared with age‐ and sex‐matched population peers (SIR 2.15 [93% CI 1.84–2.49]), especially for lung cancer (SIR 2.12 [95% CI 1.21–3.44]), early breast cancer (SIR 3.07 [95% CI 1.47– 5.64]), and early melanoma (SIR 3.40 [95%CI 1.10–7.93]), occurring independently of traditional cancer risk factors (e.g., smoking and immunosuppressive therapy).…”

“…Our epidemiologic findings are consistent with the results of recent meta‐analyses evaluating cancer risk in SSc (3–5), all showing an increased cancer risk in SSc. Consistent with the literature (3), we found an increased SIR for lung and early breast cancer, but not for liver and bladder cancer, given the low number of these cancers in our cohort (2 and 1, respectively) (3).…”

“…Some series have documented an increased risk of cancer in individuals with SSc compared with the general population, in particular an increased risk of lung, breast, and hematologic malignancies (3)(4)(5)(6). This association is thought to be driven by fibrosis, chronic inflammation, and B-cell stimulation, in addition to SSc-specific genetic factors, environmental factors, the use of immunosuppressive therapies, and cancer-driven autoimmunity, particularly in certain autoantibody profiles (6,7).…”

Effects of Radiotherapy for Malignancy in Systemic Sclerosis: A Systematic Review

“…Cancer is a known comorbidity in SSc patients, and the risk of cancer development is higher among SSc patients than in the general population [1][2][3][4][5] . Specifically, patients with SSc are at an increased risk of developing lung, hematological, head and neck malignancies 1,2,6,7 .…”