TY - JOUR
T1 - Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA)
T2 - a prospective, randomised, multicentre study
AU - Hofman, Michael S.
AU - Lawrentschuk, Nathan
AU - Francis, Roslyn J.
AU - Tang, Colin
AU - Vela, Ian
AU - Thomas, Paul
AU - Rutherford, Natalie
AU - Martin, Jarad M.
AU - Frydenberg, Mark
AU - Shakher, Ramdave
AU - Wong, Lih Ming
AU - Taubman, Kim
AU - Ting Lee, Sze
AU - Hsiao, Edward
AU - Roach, Paul
AU - Nottage, Michelle
AU - Kirkwood, Ian
AU - Hayne, Dickon
AU - Link, Emma
AU - Marusic, Petra
AU - Matera, Anetta
AU - Herschtal, Alan
AU - Iravani, Amir
AU - Hicks, Rodney J.
AU - Williams, Scott
AU - Murphy, Declan G.
N1 - Funding Information:
We thank the participants who volunteered to take part in this trial and the trial teams that cared for them, the investigators for their contribution, the Centre for Biostatistics and Clinical Trials and core imaging laboratory at the Peter MacCallum Cancer Centre for coordination of the trial, and the trial management committee for oversight of the trial. We additionally thank the following groups who contributed to the grant application or were involved in the running of this clinical trial: Australasian Radiopharmaceutical Trials Network, Australian and New Zealand Urogenital and Prostate Cancer Trials Group, Centre for Health Economics Research and Evaluation (University of Technology Sydney, Sydney, NSW, Australia), Urological Society of Australia and New Zealand, and the Trans Tasman Radiation Oncology Group Cancer Research Group. We would also like to acknowledge our consumer representative, Mark Sibree. MSH would like to acknowledge the support from a Clinical Fellowship Award from the Peter MacCallum Foundation.
Funding Information:
MSH reports grants from Prostate Cancer Foundation of Australia, Movember, and the Peter MacCallum Foundation, during the conduct of the study; other grants from Prostate Cancer Foundation, US Department of Defense, and Victorian Cancer Agency; personal fees and non-financial support from Ipsen, Sanofi Genzyme, and Jannsen, outside of the submitted work. PT reports grants from Prostate Cancer Foundation of Australia, during the conduct of the study. JMM reports grants from Mundipharma, and personal fees from Janssen and Ferring, outside of the submitted work. RJH reports stockholding from Telix Pharmaceuticals, outside of the submitted work. DGM reports personal fees from Astellas, Janssen, Bayer, Ferring, and Ipsen, outside of the submitted work. All other authors declare no competing interests.
Funding Information:
We thank the participants who volunteered to take part in this trial and the trial teams that cared for them, the investigators for their contribution, the Centre for Biostatistics and Clinical Trials and core imaging laboratory at the Peter MacCallum Cancer Centre for coordination of the trial, and the trial management committee for oversight of the trial. We additionally thank the following groups who contributed to the grant application or were involved in the running of this clinical trial: Australasian Radiopharmaceutical Trials Network, Australian and New Zealand Urogenital and Prostate Cancer Trials Group, Centre for Health Economics Research and Evaluation (University of Technology Sydney, Sydney, NSW, Australia), Urological Society of Australia and New Zealand, and the Trans Tasman Radiation Oncology Group Cancer Research Group. We would also like to acknowledge our consumer representative, Mark Sibree. MSH would like to acknowledge the support from a Clinical Fellowship Award from the Peter MacCallum Foundation.
Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/4/11
Y1 - 2020/4/11
N2 - 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% 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. Video Abstract: [Figure presented]
AB - 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% 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. Video Abstract: [Figure presented]
UR - http://www.scopus.com/inward/record.url?scp=85082773271&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(20)30314-7
DO - 10.1016/S0140-6736(20)30314-7
M3 - Article
C2 - 32209449
AN - SCOPUS:85082773271
SN - 0140-6736
VL - 395
SP - 1208
EP - 1216
JO - The Lancet
JF - The Lancet
IS - 10231
ER -