PFB-03 study protocol: diagnostic performance and clinical application of 18 F-FAPI-PET/CT for detecting axillary metastasis in breast cancer patients after neoadjuvant therapy

Objectives Axillary lymph node (ALN) status is a crucial prognostic factor in breast cancer. Accurate, non-invasive methods for evaluating axillary lymph node metastasis after neoadjuvant therapy (NAT) are needed to optimize surgical decisions and minimize patient morbidity. Fibroblast activation protein inhibitor (FAPI) PET/CT targets cancer-associated fibroblasts and may improve diagnostic accuracy. This study aims to assess the diagnostic performance and clinical utility of 18 F-FAPI PET/CT in detecting ALN metastasis after NAT in breast cancer patients. Methods This prospective, single-center study will enroll breast cancer patients with cT1-4N0-1M0 stage before NAT, who will undergo pre-surgical 18 F-FAPI PET/CT followed by sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) guided by protocol stratification based on FAPI PET/CT and clinical findings. The primary endpoint is the diagnostic accuracy of 18 F-FAPI PET/CT for ALN metastasis vs. pathology. Secondary endpoints include false-negative rates (FNR) of SLNB, lymphedema rates, and long-term outcomes such as local recurrence and survival rates. Discussion This study will provide evidence on the efficacy of 18 F-FAPI PET/CT in accurately assessing ALN status post-NAT, potentially enabling de-escalation and reducing complications, thereby advancing personalized breast cancer care. Trial registration ClinicalTrials.gov, identification number: NCT07012707.