Utility of ¹⁸F-Flotufolastat Positron Emission Tomography/Computed Tomography Imaging in High-Risk Prostate Cancer in...

This investigator-initiated, prospective, low-intervention, phase 3 study evaluated the clinical utility of prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/CT imaging with ¹⁸F-flotufolastat (formerly ¹⁸F-rhPSMA-7.3) in men with newly diagnosed high-risk prostate cancer (PCa) and negative conventional imaging. The primary end point was the rate of clinical upstaging and its effect on subsequent management.

A total of 113 treatment-naïve men meeting National Comprehensive Cancer Network high-risk criteria were enrolled; 110 underwent PSMA PET/CT with ¹⁸F-flotufolastat. Before imaging, all patients had negative conventional staging, as determined by bone scan and CT or MRI. Imaging was performed 50 to 70 minutes post injection of 8 mCi ± 20% ¹⁸F-flotufolastat. The results were interpreted by board-certified nuclear medicine physicians trained in PSMA imaging.

¹⁸F-flotufolastat identified extraprostatic disease in 36 of 110 patients (32.7%). Among them, 15 of 36 (41.7%) had isolated regional lymph node (N1) involvement, while 21 of 36 (58.3%) demonstrated distant metastatic (M1) disease. Of the patients who were upstaged, 34 of 36 patients (94.4%) had a change in their treatment plan. The most common treatment intensification included the addition of an androgen receptor inhibitor and expanded radiotherapy fields (50.0%). Furthermore, 34.3% received up-front chemotherapy alongside an androgen receptor inhibitor and radiation. A minority (8.6%) proceeded with radical prostatectomy as a first step of a multimodality approach.

PSMA PET/CT with ¹⁸F-flotufolastat led to clinical upstaging in nearly one-third of men with high-risk PCa and negative conventional imaging, resulting in significant treatment change in most patients. These findings support the integration of PSMA-targeted imaging into initial staging pathways for men with high-risk PCa.