In men with high-risk prostate cancer undergoing staging before curative-intent therapy, a multicentre, two-arm, randomised study found that a diagnostic pathway that used prostate-specific membrane antigen (PSMA) PET-CT is superior as a first-line investigation and represents a suitable replacement to conventional CT and bone scan imaging. The study findings are published on 22 March 2020 in The Lancet.
Despite selection of patients with localised prostate cancer before surgery or radiotherapy, relapse is common, partly because conventional imaging with CT and bone scan has insufficient sensitivity and specificity. Novel imaging might improve outcomes by more accurately defining disease extent, enabling a more tailored multimodal treatment plan to be proposed.
Emerging data suggest that PSMA PET-CT is an important advance for imaging prostate cancer, particularly in the setting of recurrent cancer. For primary staging, evidence is limited by retrospective or single-centre study design, without comparison with conventional imaging. Furthermore, a paucity of data exists with follow-up or comparison with a reference standard.
Prof. Michael S Hofman of the Peter MacCallum Cancer Centre in Melbourne, Australia and proPSMA Study Group Collaborators recruited in this study men with biopsy-proven prostate cancer and high-risk features at ten hospitals in Australia. Patients were randomly assigned to conventional imaging with CT and bone scanning or gallium-68 PSMA-11 PET-CT. First-line imaging was done within 21 days following randomisation. Patients crossed over unless three or more distant metastases were identified.
The study primary outcome was accuracy of first-line imaging for identifying either pelvic nodal or distant-metastatic disease defined by the receiver-operating curve using a predefined reference-standard including histopathology, imaging, and biochemistry at 6-month follow-up.
In total, 339 men were assessed for eligibility and 302 men were randomly assigned in two study arms; of those 152 (50%) men were assigned to conventional imaging and 150 (50%) to PSMA PET-CT. Of 295 (98%) men with follow-up, 87 (30%) had pelvic nodal or distant metastatic disease.
PSMA PET-CT had a 27% (95% confidence interval [CI] 23–31) greater accuracy than that of conventional imaging (92% [88–95] vs 65% [60–69]; p < 0.0001). The study team found a lower sensitivity (38% [24–52] vs 85% [74–96]) and specificity (91% [85–97] vs 98% [95–100]) for conventional imaging compared with PSMA PET-CT.
Subgroup analyses also showed the superiority of PSMA PET-CT, area under the curve of the receiver operating characteristic curve 91% vs 59% for patients with pelvic nodal metastases, and 95% vs 74% for patients with distant metastases.
First-line conventional imaging conferred management change less frequently (23 [15%] vs 41 [28%] men; p = 0.008) and had more equivocal findings (23% vs 7%) than PSMA PET-CT did.
Radiation exposure was 10.9 mSv (95% CI 9.8–12.0) higher for conventional imaging than for PSMA PET-CT (19.2 mSv vs 8.4 mSv; p < 0.001). The investigators found high reporter agreement for PSMA PET-CT (κ=0.87 for nodal and κ=0.88 for distant metastases).
In patients who underwent second-line image, management change occurred in seven (5%) of 136 patients following conventional imaging, and in 39 (27%) of 146 following PSMA PET-CT.
The authors concluded that PSMA PET-CT is a suitable replacement for conventional imaging, providing superior accuracy, to the combined findings of CT and bone scanning.
The study was funded by Movember and Prostate Cancer Foundation of Australia.
Hofman MS, Lawrentschuk N, Francis RJ, 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, multi-centre study. Lancet; Published online 22 March 2020. DOI: https://doi.org/10.1016/S0140-6736(20)30314-7