AN INTERNATIONAL registry study has identified distinct clinical and serological associations with cancer in systemic sclerosis, showing that cancer timing and site relate differently to autoantibody status, smoking, and organ involvement, with implications for surveillance strategies.
Cancer is a major cause of mortality in systemic sclerosis (SSc). Established risk factors have remained limited to specific subsets, particularly early diffuse anti-RNA polymerase III (POLR3)-positive disease. Broader predictors of cancer in systemic sclerosis have remained poorly defined.
Researchers conducted a nested case-control study within EUSTAR, the European Scleroderma Trials and Research registry, comparing 454 SSc patients who developed cancer, classified as synchronous (29%), subsequent (51%) or previous (20%) relative to SSc onset, with 454 cancer-free SSc controls matched for age and disease duration.
Mean age was 55 years (SD 13) and mean disease duration 5 years (SD 2); 88% were female, 27.5% had diffuse SSc, 30.5% had interstitial lung disease (ILD), 32% were anti-topoisomerase positive and 10% anti-POLR3 positive.
Synchronous cancers were associated with anti-POLR3 positivity (OR 2.06, 95% CI 1.13 to 3.69), U1RNP positivity (OR 3.56, 95% CI 1.03 to 12.3) and smoking (OR 1.57, 95% CI 1.01 to 2.44), but were negatively associated with digital ulcers (OR 0.55, 95% CI 0.31 to 0.93). Calcinosis was inversely associated with subsequent cancers (OR 0.42, 95% CI 0.17 to 0.93). Breast cancer showed time-dependent associations with anti-POLR3 and anti-PM/Scl antibodies. Lung cancer occurred mainly as a subsequent malignancy and was associated with ILD (OR 2.00, 95% CI 1.12 to 3.54), anti-topoisomerase positivity (OR 2.61, 95% CI 1.38 to 5.04) and smoking. Cancers occurred more frequently among patients treated with cyclophosphamide. Malignancy worsened overall survival, particularly when subsequent. Radiation therapy did not affect mortality or new-onset ILD.
These findings indicate that the timing and site of cancer in systemic sclerosis identify distinct clinical and serological profiles, each carrying different prognostic implications. Because cancers diagnosed during follow-up remain a major determinant of mortality, the results support stratified surveillance strategies tailored to antibody status, organ involvement and smoking history.
Reference
Tonutti A et al. Cancer in systemic sclerosis: clinical associations and prognostic impact from the EUSTAR registry. Arthritis & rheumatology. 2026;DOI:10.1002/art.70303.
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