Efficacy of Adjuvant Interferon-β Versus Observation for Resected Nail Apparatus Melanoma: A Multicenter Retrospective Study.

Nail apparatus melanoma (NAM) is a biologically and clinically distinct subtype of melanoma; however, the efficacy of adjuvant interferon (IFN) therapy in this population remains unclear. We conducted a multicenter retrospective study to compare adjuvant IFN-β (adj-IFN) with observation (OBS) in patients with resected stage IIB, IIC, or III NAM. We analyzed 282 Japanese patients treated at 42 institutions between 2014 and 2024. Recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) were co-primary outcomes, and overall survival (OS) was a secondary outcome. Survival outcomes were assessed using Kaplan-Meier analyses and Cox multivariable proportional hazards models. To minimize the differences of baseline characteristics between the two groups, propensity score matching (PSM) was applied. In multivariable Cox analyses, adj-IFN showed improved RFS (HR 0.67, 95% CI 0.45-0.998, p = 0.049), while no statistically significant benefits were observed for DMFS (HR 0.66, 95% CI 0.42-1.01, p = 0.06) or OS (HR 0.85, 95% CI 0.54-1.35, p = 0.50) compared with OBS. After PSM (71 patients per group), survival outcomes were comparable between the two groups, with no statistical significance in RFS (HR 0.71, 95% CI 0.45-1.12, p = 0.14), DMFS (HR 0.73, 95% CI 0.44-1.20, p = 0.22), or OS (HR 1.01, 95% CI 0.58-1.78, p = 0.96). In conclusion, no significant survival advantage of adj-IFN over observation was demonstrated in the matched cohort. Although a borderline association with improved RFS was observed in the overall cohort, this finding did not translate into consistent benefit across endpoints. Further prospective evidence, including the final results of the randomized phase III trial (JCOG1309, J-FERON), is required to clarify the clinical role of adj-IFN in NAM.