The limited performance of conventional CT and bone scanning in detecting non-localized prostate cancer during primary staging can lead to suboptimal treatment. Now, evidence from the phase III proPSMA trial indicates that prostate-specific membrane antigen (PSMA) PET–CT is a superior staging modality.

In proPSMA, 302 men with biopsy-proven high-risk localized prostate cancer were randomly assigned (1:1) to first-line imaging with either gallium-68 PSMA-11 PET–CT or conventional single-photon emission CT plus technetium-99m bone scanning. The primary outcome of the trial was the accuracy of first-line imaging for identifying pelvic nodal or distant metastatic disease, as defined by the receiver-operating curve using a predefined reference standard comprising histopathology, imaging and biochemical analyses after a follow-up duration of 6 months.

PSMA PET–CT had greater accuracy than conventional imaging (area under the curve (AUC) 92% versus 65%; P < 0.0001), reflecting the higher sensitivity and specificity of the former modality (85% versus 38% and 98% versus 91%, respectively). Subgroup analyses revealed that PSMA PET–CT was superior in the detection of both pelvic nodal metastases (AUC 91% versus 59%) and distant metastases (AUC 95% versus 74%), and yielded similar absolute improvements in accuracy independent of Gleason grade group or serum prostate-specific antigen concentration.

Accordingly, PSMA PET–CT findings more often prompted a change in treatment intent, modality or technique than did conventional imaging (28% versus 15%; P = 0.008) and resulted in fewer equivocal findings (7% versus 23%; P < 0.001). Moreover, patients were exposed to less radiation with PSMA PET–CT (8.4 mSv versus 19.2 mSv; P < 0.001), and inter-reader agreement was high (κ = 0.87–0.88).

The proPSMA trial fills a knowledge gap left by previous case series evaluating PSMA PET–CT, which lacked comparisons with a reference standard. The results of this trial indicate a suitable replacement for conventional imaging in prostate cancer staging. Health-economic analyses are required, however, to support widespread reimbursement and uptake.