Early Progression with Nodal Involvement Is a Predictor of Early Mortality in Mycosis Fungoides: A Retrospective, Registry-Based Cohort Study

Nodal involvement is a key indicator of advanced disease in mycosis fungoides (MF). While progression within 24 months is prognostic of survival in other indolent lymphomas, such clinical benchmarks in MF remain underexplored. We aimed to evaluate whether early nodal progression after the initial diagnosis serves as an independent, dynamic clinical predictor of early mortality in patients with MF. This retrospective, registry-based study utilized data from TriNetX. Evaluating post-diagnosis timepoints from 12 to 36 months, the 12-month landmark demonstrated the greatest survival divergence and was selected as the optimal threshold for early nodal progression. Patients without nodal involvement within the first 12 months served as controls. To mitigate immortal time bias, a strict 12-month landmark analysis was employed. Among 25,419 screened patients, 2132 (8.4%) developed nodal involvement within the first 12 months (NODE12). At the 12-month landmark, 21,840 patients were evaluable: 1832 with NODE12 and 20,008 controls. At this landmark, the 5-year overall survival rate was 74.8% for NODE12 patients versus 87.8% for controls (p < 0.001). In multivariable Cox regression, NODE12 was an independent predictor of early mortality (aHR = 1.97, 95% CI: 1.77–2.20, p < 0.001), alongside advanced age (aHR = 3.58, p < 0.001) and lymphocytosis (aHR = 1.69, p < 0.001). This survival disadvantage was further confirmed in the PSM sensitivity analysis of 1992 matched pairs (HR = 1.96, 95% CI: 1.66–2.31, p < 0.001). In conclusion, NODE12 is a dynamic clinical milestone identifying a high-risk MF phenotype. Similar to POD24 in B-cell lymphomas, NODE12 identifies a high-risk patient subgroup that may benefit from closer monitoring and refined risk stratification.