Cancer risk in Sjögren's disease: A longitudinal cohort study on incidence, predictors, and mortality impact

Abstract

Objectives: This study aimed to evaluate standardized incidence ratios (SIRs) of overall malignancies, hematologic malignancies and solid tumors in patients with Sjögren's disease (SjD) compared to the general population. Furthermore, it sought to identify independent predictors of malignancy and quantify the impact of cancer on mortality.

Methods: This prospective, multicenter study included 314 patients clinically diagnosed with SjD and fulfilling 2002 American-European Consensus Group criteria, with a median follow-up of 9.5 years. Clinical, demographic, and serological data were collected, along with malignancy incidence and mortality outcomes. SIRs were calculated using GLOBOCAN data. Multivariate Cox regression identified malignancy predictors. The relative risk (RR) of death and the etiologic fraction in exposed individuals (EFE) assessed cancer-related mortality.

Results: A total of 22 malignancies (7.01%) were identified, including 11 hematologic malignancies (50%) and 11 solid tumors (50%). The overall cancer risk was increased (SIR: 1.68, 95% CI: 1.68-1.69), with a substantially higher risk for hematologic malignancies (SIR: 3.55, 95% CI: 3.54-3.56) and a moderate increase for solid tumors (SIR: 1.54, 95% CI: 1.53-1.55). All hematologic malignancies were non-Hodgkin lymphomas (NHL). Independent predictors of malignancy included older age, smoking, lymphadenopathy, splenomegaly, and cryoglobulinemia. Cancer was responsible for 23.8% of deaths (RR: 2.21, EFE: 55%).

Conclusions: Patients with SjD have an elevated malignancy risk, mainly driven by NHL, while solid tumor risk remains modest. Malignancy was a significant contributor to mortality. These findings underscore the need for better risk stratification and targeted surveillance in high-risk SjD patients for early detection and intervention.

Keywords: Lymphoma; Mortality; Neoplasms; Risk Factors; Sjögren's syndrome.