A nested case-control study within the EUSTAR registry compared 454 SSc patients who developed cancer (classified as synchronous, subsequent, or previous relative to SSc onset) with 454 cancer-free SSc controls matched for age and disease duration, analyzing clinical, serological, and treatment associations as well as survival outcomes.
Synchronous cancers were linked to anti-POLR3 (OR 2.06), U1RNP (OR 3.56), and smoking (OR 1.57); lung cancer (mainly subsequent) was associated with ILD (OR 2.00), anti-topoisomerase (OR 2.61), and smoking; subsequent cancers were the strongest driver of excess mortality; radiation therapy did not increase mortality or new-onset ILD.
Retrospective registry design limits causal inference; cancer diagnoses and treatments relied on registry reporting, which may be incomplete; controls were matched only on age and disease duration, leaving residual confounding possible.
Stratify cancer surveillance in SSc by antibody profile and disease timing — patients with anti-POLR3, anti-topoisomerase, ILD, or smoking history warrant closer monitoring, especially for breast and lung cancers. Subsequent (post-diagnosis) cancers carry the worst survival impact, so ongoing surveillance beyond early disease is essential.
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