Background: Melanoma is a leading cause of cancer-related death in Australia. Body composition has emerged as a potential modifier of outcomes in metastatic melanoma, yet findings based on body mass index (BMI) remain inconsistent. CT‑derived measures may better capture biologically relevant differences in muscle and adiposity. This study investigated whether skeletal muscle mass and adiposity measured on FDG‑PET/CT are associated with outcomes in melanoma patients treated with immunotherapy.
Methods: This single‑centre retrospective study included patients with unresectable stage III/IV melanoma treated with immune checkpoint inhibitors (ICIs) at Peter MacCallum Cancer Centre (2010–2024). Baseline PET/CT scans were analysed at L3 using automated AI tools to quantify muscle and adipose compartments. BMI was categorised per WHO criteria. Survival outcomes were analysed using Kaplan–Meier methods and Cox regression, with sex‑stratified analyses performed.
Results: The cohort included 710 patients with metastatic melanoma (34% female). Most patients had good performance status (ECOG 0–1: 67%). Overall, 70% were overweight or obese, with similar BMI distributions between sexes. Despite comparable total adiposity, marked sex‑specific differences in fat distribution were observed, with males exhibiting substantially higher visceral adiposity and females higher subcutaneous adiposity. BMI was not associated with overall survival (OS) or progression‑free survival (PFS) in the overall cohort.
In sex‑stratified analyses, OS in males was associated with BMI, total and visceral adiposity in univariable analyses, while skeletal muscle remained independently associated with OS. No associations with OS and skeletal muscle or adiposity measures were observed in females. For PFS, higher visceral adiposity was independently associated with improved outcomes in both sexes. In males only, BMI, total adiposity and skeletal muscle were additionally associated with PFS. ECOG performance status remained the strongest predictor of survival and treatment response.
Conclusion: In metastatic melanoma, body composition shows sex-specific associations with outcomes. Visceral adiposity correlates with improved PFS in both sexes, while skeletal muscle independently predicts OS in males. These findings highlight the importance of incorporating sex‑specific body composition metrics, particularly adiposity, into risk stratification beyond BMI alone.
Acknowledgements: This work was supported by an NHMRC grant (#2020050) to KS.