A Prospective, Multi-site, International Comparison of F-18 fluoro-methyl-choline, multi-parametric magnetic resonance and Ga-68 HBED-CC (PSMA-11) in men with High-Risk Features and Biochemical Failure after Radical Prostatectomy: Clinical Performance and Patient Outcomes

Abstract

Background: A significant proportion of men with rising PSA following radical prostatectomy (RP) fail prostate fossa salvage radiotherapy (SRT). This study assessed the ability of F18 fluoro-methyl-choline PET/CT(FCH), Ga-68 HBED-CC PSMA-11 PET/CT (PSMA) and pelvic multi-parametric magnetic resonance imaging (pelvic MRI) to identify men who will best benefit from SRT. Methods: Prospective, multisite, imaging study in men with rising PSA post RP, high-risk features (PSA > 0.2ng/mL and either Gleason Score (GS) > 7 or PSA doubling time <10 months, or PSA >1.0ng/mL) and negative /equivocal conventional imaging (CT and bone scan) being considered for SRT. FCH (91/91), Pelvic MRI (88/91) and PSMA (31/91) (Australia only) were performed within two weeks. Imaging was interpreted by experienced local and central reads blinded to other imaging results with consensus for discordance. Imaging results were validated using a composite reference standard. Expected management was documented pre and post- imaging, and all treatments, biopsies and PSA collected for 3 years. Treatment response to SRT was defined as > 50% PSA reduction without androgen deprivation therapy. Results: Median GS, PSA at imaging and PSA doubling time were 8, 0.42(IQR 0.29-0.93) ng/mL, and 5.0 (IQR 3.3-7.6) months, respectively. Overall recurrent PCa was detected in 28% (25/88) with pelvic MRI, 32% (29/91) FCH and 42% (13/31) PSMA. This was within the prostate fossa (PF) in 21.5% (19/88), 13% (12/91) and 19% (6/31), with extra PF sites in 8% (7/88), 19% (17/91), and 32% (10/31) for MRI, FCH and PSMA (< 0.004). 94% (16/17) extra- PF sites on FCH were within the field of view of pelvic MRI. The detection rate for intrapelvic extra-PF disease was 90% (9/10) for PSMA and 31% (5/16) for MRI compared to FCH. Imaging changed expected management in 46% (42/91) FCH, and 23% (21/88) MRI. PSMA provided additive management change over FCH in a further 23% (7/31). Treatment response to SRT was higher in men with negative or PF confined vs. extra PF disease. FCH 73% (32/44) vs. 33% (3/9) (p< 0.02), pelvic MRI 70% (32/46) vs 50% (2/4), P = ns) and PSMA 88% (7/8) vs. 14% (1/7) (p<0.005). Men with negative imging (MRI, FCH +/- PSMA) had high (78%) response rates to SRT. Conclusion: FCH and PSMA had high detection rates for extra PF disease in men with negative/equivocal conventional imaging and BCR post RP. This impacted management and treatment responses to SRT, suggesting an important role for PET in triaging men being considered for curative SRT.