Addition of 18F-DCFPyL PSMA PET to MRI to avoid unnecessary biopsy in men on active surveillance: Final results from a phase II diagnostic trial (PROMPT).

5125 Background: Multiparametric MRI (mpMRI) is used in active surveillance (AS) for prostate cancer (PC) but has limited specificity. This prospective trial evaluated whether combining 18F-DCFPyL PSMA PET with mpMRI improves the detection of clinically significant PC (csPC) in patients on AS and reduces unnecessary biopsies prompted by false-positive mpMRI. Methods: In this IRB-approved, single-arm Phase II study, 91 patients on AS underwent PSMA PET and mpMRI on a dedicated PET/MRI scanner followed by systematic and targeted biopsies. PET and mpMRI were interpreted independently. The primary outcome was the diagnostic accuracy of mpMRI versus the combined PSMA PET/MRI for csPC. Results: Among 246 targeted lesions, the area under the curve (AUC) for combined PSMA PET/MRI was (0.77) compared to mpMRI alone (0.70) (p=0.2). PSMA PET/MRI showed improved specificity (64.6% vs. 27.5%) with a comparable negative predictive value (89.1% vs. 89.7%). Of 57 csPC lesions, 6 (10.5%) were uniquely identified by the combination. Half of the biopsies for false-positive mpMRI or PET lesions (122/246; 50%) encompassing 17/91 (19%) of patients could have been avoided with combined imaging. Management changed in 9% of patients based on PET/MRI. Conclusions: In this first-in-field trial the addition of PSMA PET to mpMRI with dedicated PET/MRI imaging enhances sensitivity in detecting csPC and may reduce the need for unnecessary biopsies in AS patients. Incorporating PSMA PET/MRI into clinical practice could refine surveillance protocols and support biopsy omission in select men with negative imaging. The single health-system nature of the trial may limit the generalizability of our findings. Diagnostic accuracy of the mpMRI, PSMA PET/MRI, and for the combination, assessed using the “AND” operator. a Parameter MRI, PIRADS≥3 PSMA-PET, Likert≥3 MRI, PIRADS≥4 PSMA-PET, Likert≥4 MRI PIRADS≥3 ANDPET Likert≥3 MRI PIRADS≥3 ANDPET Likert≥4 MRI PIRADS≥4 ANDPET Likert≥3 MRI PIRADS≥4 ANDPET Likert≥4 Accuracy 41.9% 48.0% 63.8% 63.8% 66.7% 72.8% 78.5% 79.3% Sensitivity 89.5% 84.2% 71.9% 73.7% 73.7% 64.9% 63.2% 57.9% Specificity 27.5% 37.0% 61.4% 60.8% 64.6% 75.1% 83.1% 85.7% PPV 27.1% 28.7% 36.0% 36.2% 38.5% 44.0% 52.9% 55.0% NPV 89.7% 88.6% 87.9% 88.5% 89.1% 87.7% 88.2% 87.1% Number of lesions (% of 257) 188 (76) 167 (68) 114 (46) 116 (47) 109 (44) 84 (34) 68 (28) 60 (24) a The detection of clinically significant cancer was considered on per-lesion analysis. MRI = magnetic resonance imaging; PET = positron emission tomography; PI-RADS = Prostate Imaging Reporting and Data System; PSA = prostate-specific antigen; PSMA = prostate-specific membrane antigen. PPV= positive predictive value, NPV = negative predictive value.