A revised staging system for natural killer/T cell lymphoma incorporating skull base invasion and nasal/non-nasal subtype distinction

Current staging systems for natural killer/T cell lymphoma (NKTCL) inadequately reflect its predominantly extranodal presentation and lack prognostic accuracy in the asparaginase era. This retrospective multicenter study analyzes 1,872 newly diagnosed NKTCL patients treated with asparaginase-based regimens or radiotherapy alone, from 15 institutions across China. For nasal-type NKTCL, skull base invasion (SBI) is identified as an independent adverse prognostic factor. We reclassify Ann Arbor stage I patients with SBI as stage II and stage II patients with SBI as stage III. For non-nasal-type NKTCL, we retain the Chinese Southwest Oncology Group and Asia Lymphoma Study Group (CA) system due to its superior prognostic discrimination. The revised system demonstrates improved outcome prediction, hazard discrimination, hazard consistency, and sample balance across training, internal, and external validation cohorts. Time-dependent receiver operating characteristic (ROC) analysis confirms superior predictive accuracy over existing systems. This proposal provides a refined prognostic framework to guide clinical decision-making and optimize patient selection for future trials.