Phase II study of uPAR-PET/CT for staging of primary breast cancer in comparison with ultrasound and fine needle biopsies.

Accurate initial staging of patients with breast cancer is essential for planning optimal treatment strategies. However, currently, no imaging modality is able to detect lymph node metastases preoperatively with sufficient reliability; therefore, the N status depends on the sentinel node procedure for ~ 70% of patients. In a prospective clinical trial of breast cancer patients, we compared head-to-head uPAR-PET/CT with current standard-of-care, ultrasound (US) and fine needle biopsy (FNB) as staging methods. Forty-nine patients (48 women and 1 man) with biopsy-proven early breast cancer underwent uPAR-PET/CT prior to surgery. All image data were analyzed by two separate teams, each consisting of a highly experienced certified specialist in nuclear medicine and a highly experienced certified specialist in radiology for visualization of primary tumor lesions and detection of lymph node and distant metastases. Histopathological assessment and verification of malignancy in the excised tissues (primary tumors and lymph nodes) were considered standard-of-truth. On a per patient basis, uPAR PET/CT demonstrated a sensitivity of 94% [CI: 83-99%] for detecting the primary tumor (both teams). For the detection of axillary lymph nodes the pooled sensitivity of uPAR PET/CT was 33.3% [CI: 16.5-54.0%], specificity 87.0% [CI: 66.4-97.2%] and accuracy 58.0% [CI: 43.2-71.8%]. In comparison, the standard-of-care preoperative clinical staging algorithm with US and FNB had a sensitivity of 41% [CI: 22-61%] and specificity of 100% [CI: 85-100%] for axillary lymph node metastases. We conclude that the results do not support the use of uPAR PET/CT for staging in breast cancer patients. However, the finding that 94% of primary tumors were uPAR-PET positive may be encouraging for pursuing uPAR theranostics in localized disease. Additionally, other potential applications, such as using uPAR-PET as a prognostic imaging biomarker of tumor aggressiveness, remain to be investigated.