Urokinase-Type Plasminogen Activator Receptor (uPAR) PET/MRI of Prostate Cancer for Noninvasive Evaluation of Aggressiveness: Comparison with Gleason Score in a Prospective Phase 2 Clinical Trial
Marie Øbro Fosbøl, Sorel Kurbegovic, Helle Hjorth Johannesen, Martin Andreas Røder, Adam E. Hansen, Jann Mortensen, Annika Loft, René Horsleben Petersen, Jacob Madsen, Klaus Brasso, Andreas Kjær
Abstract
The aim of this study was to evaluate the correlation between uptake of the PET ligand 68 Ga-NOTA-AE105, targeting the urokinase-type plasminogen activator receptor (uPAR), and Gleason score in patients undergoing prostate biopsy. Methods: Patients with clinical suspicion of prostate cancer (PCa) or previously diagnosed with PCa were prospectively enrolled in this phase 2 trial. A combination of uPAR PET and multiparametric MRI (mpMRI) was performed, and the SUV in the primary tumor, as delineated by mpMRI, was measured by 2 independent readers. The correlation between the SUV and the Gleason score obtained by biopsy was assessed. Results: A total of 27 patients had histologically verified PCa visible on mpMRI and constituted the study population. There was a positive correlation between the SUV max and the Gleason score (Spearman 5 0.55; P 5 0.003). Receiver operating characteristic analysis showed an area under the curve of 0.88 (95% CI, 0.67-1.00) for discriminating a Gleason score of greater than or equal to 3 1 4 from a Gleason score of less than or equal to 3 1 3. A cutoff for the tumor SUV max could be established with a sensitivity of 96% (79%-99%) and a specificity of 75% (30%-95%) for detecting a Gleason score of greater than or equal to 3 1 4. For discriminating a Gleason score of greater than or equal to 4 1 3 from a Gleason score of less than or equal to 3 1 4, a cutoff could be established for detecting a Gleason score of greater than or equal to 4 1 3 with a sensitivity of 93% (69%-99%) and a specificity of 62% (36%-82%). Conclusion: SUV measurements from uPAR PET in primary tumors, as delineated by mpMRI, showed a significant correlation with the Gleason score, and the tumor SUV max was able to discriminate between low-risk Gleason score profiles and intermediate risk Gleason score profiles with a high diagnostic accuracy. Consequently, uPAR PET/MRI could be a promising method for the noninvasive evaluation of PCa and might reduce the need for repeated biopsies (e.g., in active surveillance).