In an Australian phase III trial (proPSMA) reported in The Lancet, Michael S. Hofman, MBBS, and colleagues found that gallium-68 prostate-specific membrane antigen-11 positron-emission tomography/computed tomography (PSMA PET/CT) provided greater accuracy in identifying nodal and distant metastases vs conventional imaging with CT and bone scanning prior to curative-intent surgery or radiotherapy in men with high-risk prostate cancer.
“PSMA PET/CT is a suitable replacement for conventional imaging, providing superior accuracy, to the combined findings of CT and bone scanning.”— Michael S. Hofman, MBBS, and colleagues
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Study Details
In the open-label multicenter trial, 302 patients were randomly assigned between March 2017 and November 2018 to receive first-line imaging with PSMA PET/CT (n = 150) or conventional imaging (n = 152). Patients crossed over unless three or more distant metastases were identified.
The primary outcome measure was accuracy of first-line imaging in identifying pelvic nodal or distant metastatic disease defined by receiver-operating characteristic area under the curve (AUC) using a predefined reference standard including histopathology, imaging, and biochemistry at 6-month follow-up.
Key Findings
Among 295 patients (98%) with follow-up, 87 (30%) had pelvic nodal or distant metastatic disease. AUC values for identifying such metastases were 92% with PSMA PET/CT vs 65% with conventional imaging (absolute 27% difference, P < .0001). AUC values were 91% vs 59% for patients with pelvic nodal metastases and 95% vs 74% for those with distant metastases. For PSMA PET/CT vs conventional imaging, sensitivity was 85% vs 38% and specificity was 98% vs 91%.
First-line PSMA PET/CT vs conventional imaging was associated with change in management (eg, change from curative- to palliative-intent treatment, change in radiotherapy technique, or change in surgical technique) in 28% vs 15% of patients (P = .008) and was associated with a lower percentage of equivocal findings (7% vs 23%, P < .001).
Radiation exposure was higher with PSMA PET/CT (19.2 mSv vs 8.4 mSv, P < .001). No adverse events were reported with gallium-68 PSMA-11 administration.
A high degree of reporter agreement for PSMA PET/CT was observed for nodal (κ = 0.87) and distant (κ = 0.88) metastases.
In patients crossing over to second-line imaging, management changes occurred in 39 (27%) of 146 after PSMA PET/CT vs 7 (5%) of 136 after conventional imaging.
The investigators concluded, “PSMA PET/CT is a suitable replacement for conventional imaging, providing superior accuracy, to the combined findings of CT and bone scanning.”
Dr. Hofman, of the Department of Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, is the corresponding author for The Lancet article.
Disclosure: The study was supported by Movember and Prostate Cancer Foundation of Australia. For full disclosures of the study authors, visit thelancet.com.
