Michael S Hofman1, Nathan Lawrentschuk2, Roslyn J Francis3, Colin Tang4, Ian Vela5, Paul Thomas6, Natalie Rutherford7, Jarad M Martin8, Mark Frydenberg9, Ramdave Shakher10, Lih-Ming Wong11, Kim Taubman12, Sze Ting Lee13, Edward Hsiao14, Paul Roach14, Michelle Nottage15, Ian Kirkwood16, Dickon Hayne17, Emma Link18, Petra Marusic19, Anetta Matera20, Alan Herschtal20, Amir Iravani21, Rodney J Hicks21, Scott Williams22, Declan G Murphy23. 1. Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia. Electronic address: michael.hofman@petermac.org. 2. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia; Department of Surgery, Austin Health, Melbourne, VIC, Australia; Urological Society of Australia and New Zealand, NSW, Australia. 3. Department of Nuclear Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia; University of Western Australia, Faculty of Health and Medical Sciences, Perth, WA, Australia; ARTnet, NSW, Australia. 4. Department of Radiation Oncology, Sir Charles Gairdner Hospital, Perth, Australia. 5. Department of Urology, Princess Alexandra Hospital, Australian Prostate Cancer Research Centre-Queensland, Queensland University of Technology, Translational Research Institute, Brisbane, QLD, Australia. 6. Department of Nuclear Medicine, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia; Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia. 7. Department of Nuclear Medicine, Hunter New England Health, Newcastle, NSW, Australia. 8. School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia. 9. Department of Surgery, Monash University and Cabrini Institute, Cabrini Health, Melbourne, VIC, Australia. 10. Monash Health Imaging, Monash Health, Melbourne, VIC, Australia. 11. Department of Urology and Surgery, St Vincent's Health Melbourne, University of Melbourne, Melbourne, VIC, Australia. 12. Department of Medical Imaging, PET/CT and St Vincent's Private Radiology, St Vincent's Health, Melbourne, VIC, Australia. 13. Department of Molecular Imaging and Therapy, Austin Health, Melbourne, VIC, Australia. 14. University of Sydney, Department of Nuclear Medicine and PET, Royal North Shore Hospital, Sydney, NSW, Australia. 15. Clinical and Research Imaging Centre, South Australian Health and Medical Research Institute, Adelaide, SA, Australia; Dr Jones and Partners Medical Imaging, Adelaide, SA, Australia. 16. Department of Nuclear Medicine and PET, Royal Adelaide Hospital, Adelaide, SA, Australia; Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia. 17. UWA Medical School, University of Western Australia, Perth, WA, Australia. 18. Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia. 19. Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. 20. Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. 21. Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia. 22. Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia; Australian and New Zealand Urogenital and Prostate Cancer Trials Group, NSW, Australia. 23. Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.
Abstract
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.
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.
Authors: Masatomo Kaneko; Dordaneh Sugano; Amir H Lebastchi; Vinay Duddalwar; Jamal Nabhani; Christopher Haiman; Inderbir S Gill; Giovanni E Cacciamani; Andre Luis Abreu Journal: Curr Urol Rep Date: 2021-03-22 Impact factor: 3.092
Authors: Constantin Lapa; Ursula Nestle; Nathalie L Albert; Christian Baues; Ambros Beer; Andreas Buck; Volker Budach; Rebecca Bütof; Stephanie E Combs; Thorsten Derlin; Matthias Eiber; Wolfgang P Fendler; Christian Furth; Cihan Gani; Eleni Gkika; Anca-L Grosu; Christoph Henkenberens; Harun Ilhan; Steffen Löck; Simone Marnitz-Schulze; Matthias Miederer; Michael Mix; Nils H Nicolay; Maximilian Niyazi; Christoph Pöttgen; Claus M Rödel; Imke Schatka; Sarah M Schwarzenboeck; Andrei S Todica; Wolfgang Weber; Simone Wegen; Thomas Wiegel; Constantinos Zamboglou; Daniel Zips; Klaus Zöphel; Sebastian Zschaeck; Daniela Thorwarth; Esther G C Troost Journal: Strahlenther Onkol Date: 2021-07-14 Impact factor: 3.621