Prognostic Impact of PET/CT-Derived Sarcopenia in Metastatic Breast Cancer Treated with CDK4/6 Inhibitors

Objective: This study aimed to evaluate the prognostic significance of positron emission tomography/computed tomography (PET/CT)-derived sarcopenia in patients with hormone receptor-positive, HER2-negative metastatic breast cancer treated with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. Methods: This retrospective single-center study included 77 patients treated between January 2018 and March 2025. Sarcopenia was assessed using skeletal muscle index (SMI) at the L3 level on fluorodeoxyglucose (FDG) PET/CT. Patients were classified as sarcopenic or non-sarcopenic. Clinical, nutritional parameters including body mass index (BMI) and prognostic nutritional index (PNI), and inflammatory parameters including pan-immune inflammation value (PIV) were analyzed. The primary endpoint was progression-free survival (PFS). Results: Sarcopenia was present in 35.1% of patients. After a median follow-up of 38 months, sarcopenic patients had significantly shorter PFS compared with non-sarcopenic patients (18 vs. 38 months; HR: 2.37, 95% CI 1.12-4.99, p = 0.02, multivariable analysis). In multivariable analysis, sarcopenia, recurrent disease, brain metastasis, and liver metastasis were independent predictors of PFS. No significant association was observed between sarcopenia and overall survival. BMI, PNI, and PIV were not associated with survival outcomes. Toxicity profiles were comparable between groups. Conclusions: PET/CT-derived sarcopenia may be a prognostic factor for PFS in patients receiving CDK4/6 inhibitors, whereas conventional nutritional and inflammatory markers are not. These findings support the clinical utility of imaging-based body composition assessment. Prospective studies incorporating functional measures of sarcopenia are warranted.