To place the single-center findings in a broader context, the authors conducted a systematic literature search on SSc and cancer risk and performed a meta-analysis of lung cancer SIRs pooled across 17 eligible studies.
A Risk That Nearly Doubles in Women
Among 180 patients followed for 2110 person-years, lung cancer was diagnosed in 12, a mean (SD) of 10.2 (5.9) years after SSc onset. The age-SIR for the full cohort was 5.1 (95% CI, 4.7-5.4), rising to 9.5 (95% CI, 8.7-10.3) in women and settling at 3.8 (95% CI, 3.5-4.1) in men. Diffuse cutaneous subtype (HR, 4.22; 95% CI, 1.03-17.35) and a smoking history (HR, 4.49; 95% CI, 1.14-17.69) were both associated with higher lung cancer risk, whereas digital ulcers were inversely associated with risk (HR, 0.13; 95% CI, 0.03-0.63). The meta-analysis of 17 studies, encompassing 27,563 patients with SSc, produced a pooled age-SIR of 3.85 (95% CI, 2.63-5.63), reinforcing the cohort’s signal at a population level.
“Long-term follow-up data from an SSc inception cohort indicate a 5-fold increased lung cancer risk in SSc, nearly doubled among female patients,” the researchers wrote, adding that further studies are warranted to inform screening strategies specific to this population.
A Modest Case Count Despite Decades of Follow-Up
Only 12 incident lung cancers were observed in the primary cohort, a small absolute number that widens the confidence intervals around subgroup estimates, including the sex-stratified SIRs. The inverse association with digital ulcers, in particular, warrants cautious interpretation given the limited event count behind it.
Heterogeneity across the 17 studies pooled in the meta-analysis, differing in population, follow-up duration, and case ascertainment, also means the pooled estimate should be read as a general signal rather than a precise risk figure applicable to any single patient population.
The findings give rheumatologists and payers a clearer rationale for discussing lung cancer screening with patients who have diffuse cutaneous SSc or a smoking history, and report being of female sex, particularly since SSc-associated interstitial lung disease already prompts regular pulmonary surveillance in many practices. Coordinating that existing imaging infrastructure with formal lung cancer screening criteria, the authors suggested, could help translate this risk signal into earlier detection.
References
Makris A, Poulia V, Bournia VK, et al. Lung cancer risk in systemic sclerosis: data from an inception cohort and meta-analysis of published studies. Clin Exp Rheumatol. 2026;44(8):1570-1581. doi:10.55563/clinexprheumatol/by5ndiNational Institute of Arthritis and Musculoskeletal and Skin Diseases. Scleroderma. NIH. Accessed October 1, 2026. https://www.niams.nih.gov/health-topics/scleroderma