Background/Purpose: Lung cancer is 50% more common in SLE patients than their sex and age-matched counterparts. Our objective was to assess lung cancer risk in SLE, comparing demographics, drug exposures, and disease activity.

Methods: We used data from a very large multi-site international SLE cohort; this preliminary analysis is based on 6 centres: Halifax, Toronto, Montreal, Winnipeg, San Francisco,  Baltimore. We used Cox proportional hazards regression to calculate the hazard ratio (HR) for lung cancer risk in SLE, relative to smoking, demographics (sex, age, race/ethnicity and time-dependent drug exposures and cumulative disease activity (based on adjusted mean SLEDAI-2K scores, assessed at baseline and annually). The adjusted mean SLEDAI score was assessed both as a continuous variable and (to aid in interpretation) and categorized using quartiles. Time zero for the observation interval was SLE diagnosis, so that our analyses adjusted for SLE duration. We included observation time and lung cancer events occurring after entry into the lupus cohort and up to the time of cohort exit (death, cancer, or date of last visits). Those developing a cancer other than lung during the interval, were censored at that time.

Results: Within the cohort (N=4,667) 34 lung cancers (7 male, 27 female) occurred. Versus SLE controls without cancer, lung cancer cases tended to be white (85.3% versus 63.3% in controls), and older at cohort entry (mean 52.3 years, median 52.9; versus mean 38.4, median 36.9 in controls). Among lung cancer cases 61.8% had high disease activity (highest SLEDAI quartile) at baseline (95% CI 43.6, 77.8), in contrast to only 40.1% (95% CI 38.6, 41.5) of SLE patients that went on to remain free of lung cancer. The vast majority (78.8%) of the lung cancer cases in SLE were ever-smokers, versus 40.7% of the SLE patients who did not develop lung cancer. The drug profiles seemed similar (in terms of steroids, immunomodulators, NSAIDs) in the SLE patients who developed lung cancer versus those who did not (though of note, none had been exposed to cyclophosphamide prior to a lung cancer). In both univariate and multivariate models, the principal factors associated with lung cancer risk were ever smoking and age. The adjusted analyses did suggest a trend for greater cancer risk in SLE patients with higher cumulative disease activity over time (HR 1.81, 0.90, 3.63) although the CI included the null value. The estimated adjusted effects of all drugs were relatively imprecise.

Conclusion: There was a trend for greater cancer risk in SLE patients with higher cumulative disease activity over time, although we saw no definite adverse effects of drugs on lung cancer risk in SLE. In particular we did not note prior cyclophosphamide exposure in the lung cancer cases. However, drug estimates were relatively imprecise. Smoking appears to be the most significant modifiable risk factor for lung cancer in SLE.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/lung-cancer-in-sle/