¹⁸F-Fluorodeoxyglucose Positron Emission Tomography for Estimating Outcomes After Initial Treatment for Metastatic Breast Cancer: A Nonrandomized Clinical Cohort Trial

Importance: Optimizing treatment decisions in metastatic breast cancer (MBC) can alleviate patients' burden and improve quality of life. Whether ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) can be used to better estimate outcomes is unknown. Objective: To evaluate clinical utility of early metabolic change on FDG-PET for improving outcome estimation compared with standard diagnostic evaluation in patients with newly diagnosed MBC. Design, Setting, and Participants: The multicenter IMPACT-MBC clinical cohort trial enrolled patients with nonrapidly progressive, newly diagnosed MBC from August 2013 to May 2018, before initiation of first-line systemic therapy. Baseline assessment included metastasis biopsy procedure and FDG-PET and CT imaging. Early FDG-PET was performed after 2 weeks of treatment, and CT response evaluation after 8 weeks. Clinical utility was defined as the ability of early FDG-PET to estimate progressive disease (PD) on CT, progression-free survival (PFS), and overall survival (OS). Data were analyzed from October 19, 2025, to February 13, 2026. Intervention: Early FDG-PET or standard-of-care (SOC) biopsy-based treatment. Main Outcomes and Measures: Clinical utility of molecular imaging to improve outcome estimation of standard diagnostics defined as the capacity to identify poor patient outcomes. Measures were PD at 8 weeks, PFS, and OS. Results: The analysis included 200 patients (median [range] age, 61 [32-84] years; 198 females [99%] and 2 males [1%]). Non-PD on early FDG-PET had a negative predictive value (NPV) of 94.7% (95% CI, 89.5%-97.4%) for non-PD on 8-week CT. This was similar in all MBC subtypes and bone-only disease. Patients with SOC treatment and non-PD on early FDG-PET (n = 133) had a median PFS of 19.4 (95% CI, 15.2-22.8) months and OS of 39.4 (95% CI, 33.7-48.3) months compared to 4.1 (95% CI, 3.3-15.5) months and 18.5 (95% 3 CI, 7.0-33.0) months, respectively (P <.001 for both). Patients with non-PD on 8-week CT but with PD on early FDG-PET had a median (IQR) PFS and OS of 9.5 (4.1-18.1) and 19.4 (8.7-33.0) months compared to 22.3 (15.3-96.1) months and 40.1 (23.4-72.7) months without PD. Conclusions and Relevance: In this clinical cohort trial of patients with nonrapidly progressive, newly diagnosed MBC before initiation of first-line systemic therapy, early FDG-PET after only 2 weeks of treatment identified patients with MBC with distinct long-term outcomes. Incorporating early FDG-PET can improve outcome estimation of standard CT assessment.