Increasing incidences in primary lung marginal zone lymphoma: A SEER database analysis.

Abstract Primary lung marginal zone lymphoma (MZL) is a rare subtype of extra-nodal MZL. It typically follows an indolent course, with surgery being the preferred treatment in the early stages (stage I and II) due to the long-term side effects of radiation on normal lung tissue. Like other indolent lymphomas, systemic treatment has shown no overall survival benefit compared to active surveillance in late-stage (stage III and IV) diseases. However, with the advent of Rituximab-based therapies, there has so far been a lack of data regarding incidence trends and factors influencing the prognosis and survival of patients with lung MZL in the post-immunotherapy era. We extracted cases of MZL with a primary site in the lung, as reported in the SEER 17 database from 2000 to 2021. Data on patient demographics, treatment modalities, and survival outcomes were evaluated. Overall survival (OS) was estimated using the Kaplan-Meier method, with group comparisons performed using log-rank tests. Multivariable analysis was conducted using Cox proportional hazards regression to identify factors associated with hazard ratios for death. A significance threshold of p < 0.05 was applied for all statistical tests. We identified a total of 2003 patients with primary lung MZL from 2000 to 2021, with a male-to-female ratio of 0.7:1 and a median age of 69 years. The incidence of primary lung MZL in the U.S. increased by 128.9%, rising from 0.56 to 1.19 per million from 2000 to 2021. The 5-year OS rate is 76%. Factors influencing OS include advanced-stage disease (HR 1.32; 95% CI, 1.1-1.59), elderly age > 60 (HR 9.0; 95% CI 4.9-16.4), and male gender (HR 1.25, 95% CI, 1.1-1.4). We assessed the outcomes of treatment types in two subgroups: early stage and advanced stage. Surgery for early-stage shows an OS benefit (HR 0.72, 95% CI, 0.58-0.88) in this analysis. Similarly, systemic therapy for advanced-stage primary lung MZL also shows benefits compared to observation (HR 0.72, 95% CI, 0.53-0.97). Primary lung MZL incidence has significantly increased over the past two decades, requiring greater awareness and highlighting the growing importance of understanding its clinical behavior and management. Prior studies focused on broader categories of primary pulmonary lymphomas like DLBCL, our analysis uniquely examines MZL. This rise may be attributed to enhanced lung cancer screening and improved tissue sampling techniques. Our analysis demonstrates advanced age, male sex, and advanced stage are significant predictors of worse OS. Surgery provided an OS benefit for early-stage disease, while systemic therapy offered improved outcomes compared to observation for advanced-stage. These findings should be considered when making treatment decisions for patients with primary lung MZL and suggest a potential role for systemic therapy in managing advanced-stage disease, even in the context of indolent lymphoma. Further studies are needed to refine treatment approaches and explore the underlying reasons for the increasing incidence.