PSMA PET-CT superior to CT plus bone scan in high-risk prostate cancer
Prostate-specific membrane antigen (PSMA) PET-CT offers superior accuracy in identifying pelvic nodal or distant-metastatic disease in men with high-risk prostate cancer and may be a suitable replacement for conventional imaging with CT combined with bone scan, according to results of the proPSMA study.
In the multicentre, two-arm, randomized trial conducted at 10 hospitals in Australia, 302 patients (median age, 68.1 years) with biopsy-proven prostate cancer and high-risk features, who were being considered for radical prostatectomy or radiotherapy with curative intent, were randomized (1:1) to undergo gallium-68 PSMA-11 PET-CT or conventional imaging with CT and bone scan. First-line imaging for both groups was done within 21 days following randomization, after which second-line cross-over imaging was done within 14 days unless ≥3 unequivocal distant metastases were identified on first-line imaging. [Lancet 2020;395:1208-1216]
PSMA PET-CT demonstrated a 27 percent higher efficacy than conventional imaging (area under the curve [AUC], 92 percent vs 65 percent; p<0.0001) in identifying pelvic nodal or distant metastatic disease. “This finding reflected a lower sensitivity [38 percent vs 85 percent] and lower specificity [91 percent vs 98 percent] for conventional imaging compared with PSMA PET-CT,” the investigators reported.
In subgroup analyses, PSMA PET-CT demonstrated a 32 percent higher accuracy over conventional imaging in patients with pelvic nodal metastases (AUC, 91 percent vs 59 percent), and a 22 percent higher accuracy in those with distant metastases (AUC, 95 percent vs 74 percent).
Equivocal findings for identifying any metastatic disease were more frequently reported with conventional imaging than PSMA PET-CT (23 percent vs 7 percent; p<0.001), with similar results shown in patients with pelvic nodal metastases (6 percent vs 1 percent) and those with distant metastases (21 percent vs 7 percent).
Importantly, first-line PSMA PET-CT more frequently conferred changes in management than first-line conventional imaging (28 percent vs 15 percent; p=0.008).
“Following first-line PSMA PET-CT, 14 percent of patients were directed from curative to palliative-intent treatment, 7 percent had a change in radiotherapy technique, and 7 percent had a change in surgical technique,” the investigators reported. “However, the cross-over design of the study limited the ability to identify specific improvements in downstream patient outcomes between the groups.”
“This randomized phase III study provides compelling evidence that PSMA PET-CT has better accuracy, with consequent management change, fewer equivocal results, and lower radiation exposure [8.4 mSv vs 19.2 mSv; p<0.001] compared with current standard-of-care imaging with CT and bone scanning in men with newly diagnosed prostate cancer,” the investigators wrote.
“PSMA PET-CT is better and can replace conventional imaging with CT and bone scan for staging men with high-risk prostate cancer before surgery or radiotherapy with curative intent. Existing guidelines should be reviewed in light of these findings,” they suggested.
With the cost of diagnostic imaging being a major component of health expenditure, the investigators also suggested further health-economic analyses to support potential reimbursement and enable widespread access to PSMA PET-CT for patients with prostate cancer. “Cost savings with PSMA PET-CT include not only the implications of a more accurate test, but also the savings from a single rather than multiple imaging tests,” they added.