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

Sep 30, 2026

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Adjuvant anti-PD-1 therapy improves recurrence-free survival in high-risk melanoma, but many patients develop immune-related adverse events. This register-based retrospective study evaluated whether immunerelated adverse events (irAEs), spleen-to-liver ratio (SLR), and bone marrow-to-liver ratio (BLR) detected by [18F]FDG-PET/CT have prognostic value. Among 122 radically resected stage III–IV patients, irAEs were common, early-onset irAEs increased recurrence risk, and SLR/BLR showed no prognostic value.

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Abstract

Background

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Article The Prognostic Value of Biomarkers Identified by [18 F]FDG-PET/CT in Patients with High-Risk Melanoma Treated with Adjuvant Immunotherapy Anne-Line Mayland Madsen 1, Oke Gerke 1,2, Christina H. Ruhlmann 2,3, Malene Grubbe Hildebrandt 1,2 and Sambavy Nadaraja 1, * Academic Editor: Andor W.J.M. Glaudemans Received: 19 November 2025 Revised: 18 December 2025 Accepted: 23 December 2025 Published: 25 December 2025 Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. 1 Department of Nuclear Medicine, Odense University Hospital, 5000 Odense, Denmark; [anne-line.mayland.madsen@rsyd.dk](anne-line.mayland.madsen@rsyd.dk) (A.-L.M.M.); [oke.gerke@rsyd.dk](oke.gerke@rsyd.dk) (O.G.) 2 Department of Clinical Research, University of Southern Denmark, 5230 Odense, Denmark 3 Department of Oncology, Odense University Hospital, 5000 Odense, Denmark * Correspondence: [sambavy.nadaraja@rsyd.dk](sambavy.nadaraja@rsyd.dk) Abstract Background: Adjuvant anti-PD-1 therapy improves recurrence-free survival (RFS) in highrisk melanoma, but many patients experience adverse events. 2-deoxy-2-[18F]fluoro-Dglucose 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 immunerelated 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 theadjuvant setting. Keywords: adjuvant immunotherapy; anti-PD-1; biomarker; bone marrow-to-liver ratio; FDG-PET/CT; immune-related adverse events; melanoma; molecular imaging; spleen-toliver ratio 1. Introduction The introduction of adjuvant treatment with immune checkpoint inhibitors (ICIs), such as programmed cell death protein 1 monoclonal antibodies (anti-PD-1), has improved recurrence-free survival (RFS) in high-risk melanoma patients [1–4], but not all patients benefit from the treatment. In the setting of patients undergoing adjuvant treatment, patients are considered melanoma-free, as the visible tumor tissue has been surgically removed. Therefore, an analysis of response to anti-PD-1 in this patient setting is not possible. However, a recent study in patients with resected stage III melanoma receiving nivolumab as adjuvant treatment reported that number needed to treat (NNT) at four years was 4.2 for RFS and 8.5 for overall survival (OS) [5] . This means that a substantial number of patients receiving adjuvant treatm

FAQs

Which biomarkers were assessed for prognostic value in the study?

The study assessed PET/CT-detected immune-related adverse events (irAEs), spleen-to-liver ratio (SLR), and bone marrow-to-liver ratio (BLR). These were evaluated for associations with recurrence-free survival and overall survival.

What did the study find regarding irAEs and overall survival?

No association was found between irAEs and overall survival in the analysis. PET-detected irAEs were common, but they did not predict OS.

How were early-onset irAEs related to recurrence risk?

Early-onset irAEs were linked to a higher risk of recurrence within the first 1.5 years of follow-up, with a hazard ratio of 2.93 (p = 0.032).

Did SLR or BLR provide prognostic value?

No. In multivariable models, neither SLR nor BLR showed significant associations with recurrence-free survival or overall survival.

Sep 30, 2026

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