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

Background: Conventional imaging using CT and bone scan has insufficient sensitivity when staging men with high-risk localised prostate cancer. We aimed to investigate whether novel imaging using prostate-specific membrane antigen (PSMA) PET-CT might improve accuracy and affect management.

Methods: In this multicentre, two-arm, randomised study, we recruited 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 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. This trial is registered with the Australian New Zealand Clinical Trials Registry, ANZCTR12617000005358.

Findings: From March 22, 2017 to Nov 02, 2018, 339 men were assessed for eligibility and 302 men were randomly assigned. 152 (50%) men were randomly 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). We 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% [32% absolute difference; 28–35] for patients with pelvic nodal metastases, and 95% vs 74% [22% absolute difference; 18–26] for patients with distant metastases). First-line conventional imaging conferred management change less frequently (23 [15%] men [10–22] vs 41 [28%] men [21–36]; p=0·008) and had more equivocal findings (23% [17–31] vs 7% [4–13]) 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). We 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.

Interpretation: PSMA PET-CT is a suitable replacement for conventional imaging, providing superior accuracy, to the combined findings of CT and bone scanning.

Funding: Movember and Prostate Cancer Foundation of Australia


Prof Michael S Hofman, MBBS1,2, Nathan Lawrentschuk, MBBS2-4, Roslyn J Francis, MBBS5,6, Colin Tang, MBBS7, Ian Vela, MBBS8, Paul Thomas, MBBS9,10, Natalie Rutherford, MD11, Jarad M Martin, DMed12, Prof Mark Frydenberg, MBBS13, Ramdave Shakher, MBBS14, Lih-Ming Wong, MBBS15, Kim Taubman, MBBS16, Sze Ting Lee, MBBS17, Edward Hsiao, MBBCh18, Paul Roach, MBBS18, Michelle Nottage, MBBS19,20, Ian Kirkwood, MBBS21,22, Prof Dickon Hayne, MBBS23, Emma Link, DPhil1,24, Petra Marusic, BSc1, Anetta Matera, MSc24, Alan Herschtal, PhD24, Amir Iravani, MD1,2, Prof Rodney J Hicks, MBBS1,2, Prof Scott Williams, MBBS2,25,26, Prof Declan G Murphy, MBBCh2,27, for the proPSMA Study Group Collaborators

Author Affiliations:

1. Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
2. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia
3. Department of Surgery, Austin Health, Melbourne, VIC, Australia
4. Urological Society of Australia and New Zealand, NSW, Australia
5. Department of Nuclear Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia
6. University of Western Australia, Faculty of Health and Medical Sciences, Perth, WA, Australia
7. Department of Radiation Oncology, Sir Charles Gairdner Hospital, Perth, Australia
8. Department of Urology, Princess Alexandra Hospital, Australian Prostate Cancer Research Centre–Queensland, Queensland University of Technology, Translational Research Institute, Brisbane, QLD, Australia
9. Department of Nuclear Medicine, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia
10. Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia
11. Department of Nuclear Medicine, Hunter New England Health, Newcastle, NSW, Australia
12. School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
13. Department of Surgery, Monash University and Cabrini Institute, Cabrini Health, Melbourne, VIC, Australia
14. Monash Health Imaging, Monash Health, Melbourne, VIC, Australia
15. Department of Urology and Surgery, St Vincent's Health Melbourne, University of Melbourne, Melbourne, VIC, Australia
16. Department of Medical Imaging, PET/CT and St Vincent's Private Radiology, St Vincent's Health, Melbourne, VIC, Australia
17. Department of Molecular Imaging and Therapy, Austin Health, Melbourne, VIC, Australia
18. University of Sydney, Department of Nuclear Medicine and PET, Royal North Shore Hospital, Sydney, NSW, Australia
19. Clinical and Research Imaging Centre, South Australian Health and Medical Research Institute, Adelaide, SA, Australia
20. Dr Jones and Partners Medical Imaging, Adelaide, SA, Australia
21. Department of Nuclear Medicine and PET, Royal Adelaide Hospital, Adelaide, SA, Australia
22. Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia
23. UWA Medical School, University of Western Australia, Perth, WA, Australia
24. Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
25. Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
26. Australian and New Zealand Urogenital and Prostate Cancer Trials Group, NSW, Australia
27. Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

Hofman, Michael S, Nathan Lawrentschuk, Roslyn J Francis, Colin Tang, Ian Vela, Paul Thomas, and Natalie Rutherford et al. 2020. "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". The Lancet. doi:10.1016/s0140-6736(20)30314-7.

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