Cancer Development in Sjögren's Syndrome: Prognostic Factors and Clinical Implications

We read with great interest the study by Peng et al. on the mortality and survival analysis in patients with cancer occurrence after Sjögren's syndrome (SS-CA), which provides valuable insights into the long-term prognosis of this vulnerable population [1]. Their findings underscore the significant impact of malignancy on survival outcomes in patients with SS, with a standard mortality ratio (SMR) of 2.61 and markedly reduced overall survival compared to controls. Sjögren's syndrome is a systemic autoimmune disease characterized by lymphocytic infiltration of exocrine glands and diverse extraglandular manifestations [2]. The chronic inflammatory milieu and persistent immune activation in SS contribute not only to organ damage, such as renal involvement [3], but also to an increased risk of hematologic malignancies, particularly non-Hodgkin lymphoma. This has been well recognized and remains one of the most severe complications in the disease course [4]. Peng et al.'s demonstration that a short interval between SS diagnosis and cancer onset (≤ 3 years) and the presence of hematological malignancies are strong predictors of poor survival aligns with previous knowledge regarding the pathophysiological burden of uncontrolled lymphoproliferation in SS [2, 5]. It is also worth noting that the age at SS diagnosis may not reflect the true onset of the disease, as many patients experience sicca syndrome symptoms for years prior to receiving a formal diagnosis. This diagnostic delay complicates both clinical management and trial design, especially when attempting to define early disease. Age at SS diagnosis above 50 years, identified as another independent predictor of worse prognosis, suggests that early disease recognition and monitoring for malignancy are essential, especially in older patients. Moreover, pulmonary complications, including pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD), have been increasingly reported in SS patients, contributing to overall morbidity and mortality [6]. Recently, consensus guidelines for the evaluation and management of pulmonary disease in Sjögren's syndrome have been published, offering structured recommendations for diagnosis and follow-up. Future studies will need to assess whether the implementation of these guidelines improves outcomes in real-world clinical practice [7]. Cardiovascular risk factors and PAH, in particular, might act synergistically with cancer to further worsen outcomes [8]. The association between PAH and a higher risk of death in autoimmune diseases, such as SS, points to the need for comprehensive cardiovascular evaluation in these patients [9]. Another important point to consider is the variability of clinical manifestations and the heterogeneity of SS presentations across different populations, as evidenced by prior studies on the prevalence of sicca syndrome symptoms and secondary SS in rheumatoid arthritis patients. Although several algorithms have been developed to predict lymphoma risk based on clinical and serological features, there is currently no validated tool to assess cancer risk more broadly in patients with SS. Such variability might influence the risk and type of malignancy and needs to be factored into individualized risk assessments [5-10]. In conclusion, Peng et al.'s study highlights the importance of vigilance in monitoring SS patients for early signs of malignancy, particularly within the first 3 years after SS diagnosis. A multidisciplinary approach, incorporating rheumatology, oncology, and cardiology expertise, is paramount for optimizing outcomes in this complex patient population. All authors contributed equally to this work. The authors declare no conflicts of interest. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.