Labeled prostate-specific membrane antigen (PSMA) in PET-CT fusion (PSMA PET-CT) was superior in specificity and sensitivity to conventional imaging in pre-treatment staging of intermediate and high-risk localized prostate cancer.
Prof. Michael Hofman (Peter MacCallum Cancer Centre, Melbourne, Australia) presented the results of the ProPSMA study1 which was recently also published in The Lancet2. The rationale of the study, Prof. Hofman explained, was that pre-treatment staging of intermediate- and high-risk localized prostate cancer is important for treatment choice, yet current standard imaging has limited sensitivity. The study presented here investigated whether imaging using PSMA PET-CT was superior to conventional imaging in pretreatment staging.
Men with histologically confirmed prostate cancer who were being considered for curative-intent radical prostatectomy or radiotherapy (n=302) were randomly allocated to either conventional imaging using bone scan and CT per standard of care (n=152) or gallium-68 PSMA-11 PET-CT (n=150), stratified by study site. In patients with <3 unequivocal sites of metastasis, cross-over imaging for confirmation was performed within 14 days, which occurred in 96% of the patients in the conventional imaging arm. The primary endpoint was the accuracy of first-line diagnostic imaging for the identification of either pelvic nodal or distant metastatic disease, using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. The reference standard was a composite panel of histopathology, imaging, clinical, and biochemical characteristics.
Reporter agreement was high for both nodal (kappa 0.87; 95% CI 0.81-0.94) and distant metastatic disease (kappa 0.88; 95% CI 0.94-0.92) across sites. In the primary outcome assessment, PSMA PET-CT had a 27% absolute greater AUC for accuracy compared to conventional imaging (92% vs 65%; 95% CI 23-31; P<0.001). Conventional imaging had both a lower sensitivity (38% vs 85%) and a lower specificity (91% vs 98%). Further posthoc subgroup analysis showed an incremental benefit for PSMA PET-CT in men with Gleason Grade Group (GGG) 4-5 disease, those with GGG ≤3, and those with a PSA of ≥20 ng/mL.
The clinical value of PSMA PET-CT was analyzed by treatment changes that occurred as a result of pre-treatment staging imaging. In the conventional imaging arm, 23 men had a consequent treatment change (15%; 95% CI 10-22) as compared to 41 men in the PSMA PET-CT arm (28%; 95% CI 21-36). These changes included both a transition from curative intent to palliative intent treatment in 20 patients (14%), as well as a change in treatment approach in 22 men (14%).
With regard to safety, patients receiving conventional imaging had higher radiation exposure compared with PSMA PET-CT (19.2 mSv vs 8.4 mSv; 95% CI 9.8-12.0). PSMA PET-CT was not associated with any adverse events.
1. Hofman M, et al. ProPSMA Study: a prospective randomised multi-centre study of PSMA-PET/CT imaging for staging high risk prostate cancer prior to curative-intent surgery or radiotherapy. EAU20 Virtual Congress, 17-26 July 2020, Game-changing Session 1.
2. Hofman MS, et al. Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study. Lancet. 2020;395(10231):1208-1216.