The Prognostic Value of Biomarkers Identified by [18F]FDG-PET/CT in Patients with High-Risk Melanoma Treated with Adjuvant Immunotherapy.

Background: Adjuvant anti-PD-1 therapy improves recurrence-free survival (RFS) in high-risk melanoma, but many patients experience adverse events. 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography with computed tomography [18F]FDG-PET/CT has been proposed to identify biomarkers that may predict outcome of treatment. Objectives: The aim of this register-based study was to investigate the prognostic value of immune-related adverse events (irAEs), spleen-to-liver ratio (SLR), and bone marrow-to-liver ratio (BLR), detected by [18F]FDG-PET/CT. Methods: This retrospective, register-based cohort study included 122 patients with radically resected stage III-IV melanoma treated with adjuvant anti-PD-1. Patient data were extracted from a Danish register, and measurements for SLR and BLR were made using an AI model. Cox regression models were made on irAEs and BLR to assess associations with RFS and overall survival (OS). Results: Over half of the patients experienced recurrence, and one quarter died during follow-up of 4 ¾ years. Seventy-four percent exhibited at least one PET-detected irAE. This study found no association between irAEs and OS. Regarding RFS, our findings suggest an increased risk of recurrence for the presence of irAEs within the first 1.5 years of follow-up (HR: 2.93, CI: 1.10-7.84, p = 0.032). BLR and SLR were not associated with RFS or OS in multivariable models. Conclusions: This study did not confirm the findings of a positive association between irAEs and survival found in previous studies. PET-detected irAEs were common in the study population, but did not predict OS, while early-onset irAEs were linked to increased recurrence risk. Neither SLR nor BLR demonstrated prognostic value. Further research is needed to clarify the clinical utility of PET-derived biomarkers, especially in the adjuvant setting.