Prospective Comparison of 18F-Fluoromethylcholine Versus 68Ga-PSMA PET/CT in Prostate Cancer Patients Who Have Rising PSA After Curative Treatment and Are Being Considered for Targeted Therapy

In prostate cancer with biochemical failure after therapy, current imaging techniques have a low detection rate at the prostate-specific antigen (PSA) levels at which targeted salvage therapy is effective. 11C-choline and 18F-fluoromethylcholine, though widely used, have poor sensitivity at low PSA levels. 68Ga-PSMA (Glu-NH-CO-NH-Lys-(Ahx)-[68Ga-N,N′-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N′-diacetic acid]) has shown promising results in retrospective trials. Our aim was to prospectively compare the detection rates of 68Ga-PSMA versus 18F-fluoromethylcholine PET/CT in men who were initially managed with radical prostatectomy, radiation treatment, or both and were being considered for targeted therapy. Methods: A sample of men with a rising PSA level after treatment, eligible for targeted treatment, was prospectively included. Patients on systemic treatment were excluded. 68Ga-PSMA, 18F-fluoromethylcholine PET/CT, and diagnostic CT were performed sequentially on all patients between January and April 2015, and the images were assessed by masked, experienced interpreters. The findings and their impact on management were documented, together with the results of histologic follow-up when feasible. Results: In total, 38 patients were enrolled. Of these, 34 (89%) had undergone radical prostatectomy and 4 (11%) had undergone radiation treatment. Twelve (32%) had undergone salvage radiation treatment after primary radical prostatectomy. The mean PSA level was 1.74 ± 2.54 ng/mL. The scan results were positive in 26 patients (68%) and negative with both tracers in 12 patients (32%). Of the 26 positive scans, 14 (54%) were positive with 68Ga-PSMA alone, 11 (42%) with both 18F-fluoromethylcholine and 68Ga-PSMA, and only 1 (4%) with 18F-fluoromethylcholine alone. When PSA was below 0.5 ng/mL, the detection rate was 50% for 68Ga-PSMA versus 12.5% for 18F-fluoromethylcholine. When PSA was 0.5–2.0 ng/mL, the detection rate was 69% for 68Ga-PSMA versus 31% for 18F-fluoromethylcholine, and when PSA was above 2.0, the detection rate was 86% for 68Ga-PSMA versus 57% for 18F-fluoromethylcholine. On lesion-based analysis, 68Ga-PSMA detected more lesions than 18F-fluoromethylcholine (59 vs. 29, P < 0.001). The tumor-to-background ratio in positive scans was higher for 68Ga-PSMA than for 18F-fluoromethylcholine (28.6 for 68Ga-PSMA vs. 9.4 for 18F-fluoromethylcholine, P < 0.001). There was a 63% (24/38 patients) management impact, with 54% (13/24 patients) being due to 68Ga-PSMA imaging alone. Histologic follow-up was available for 9 of 38 patients (24%), and 9 of 9 68Ga-PSMA–positive lesions were consistent with prostate cancer (68Ga-PSMA was true-positive). The lesion positive on 18F-fluoromethylcholine imaging and negative on 68Ga-PSMA imaging was shown at biopsy to be a false-positive 18F-fluoromethylcholine finding (68Ga-PSMA was true-negative). Conclusion: In patients with biochemical failure and a low PSA level, 68Ga-PSMA demonstrated a significantly higher detection rate than 18F-fluoromethylcholine and a high overall impact on management.