Lung cancer risk in systemic sclerosis: data from an inception cohort and meta-analysis of published studies

Population-based cohort studies show an association between systemic sclerosis (SSc) and lung cancer; however, a Mendelian randomisation analysis refutes causality. Herein, lung cancer risk is analysed in an academic inception SSc cohort, complemented by a meta-analysis of published data.

Patients evaluated within 12 months of SSc onset, between January 1995 and December 2020, with regular follow-up until December 2024, were included. Clinical manifestations, laboratory parameters, treatments and comorbidities were prospectively recorded. Age-standardised incidence ratio (SIR) of lung cancer was estimated using the Global Cancer Observatory database. Lung cancer determinants were evaluated with Cox proportional hazards models. A systematic literature search for the association between SSc and cancer and a meta-analysis of lung cancer SIRs from eligible studies was conducted.

Among 180 patients (2,110 person-years follow-up), lung cancer was diagnosed in 12, after a mean 10.2±5.9 years from SSc onset. Age-SIR was 5.1 (95% CI 4.7-5.4) for the entire cohort, 3.8 (95% CI 3.5-4.1) for male and 9.5 (95% CI 8.7-10.3) for female patients. Diffuse subtype [HR = 4.22, 95% CI: 1.03-17.35] and smoking history [HR=4.49, 95% CI: 1.14-17.69] were associated with lung cancer development, whereas digital ulcers were inversely associated [HR: 0.13, 95% CI: 0.03-0.63]. The meta-analysis of 17 studies (27,563 SSc patients) yielded a pooled lung cancer age-SIR of 3.85 [95% CI (2.63-5.63)].

Long-term follow-up data from an SSc inception cohort indicate a fivefold increased lung cancer risk in SSc, nearly doubled among female patients. Further studies are warranted to inform screening strategies.