Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study

• Published in: The Lancet (British edition) 2020-04, Vol.395 (10231), p.1208-1216
• Main Authors: Hofman, Michael S, Lawrentschuk, Nathan, Francis, Roslyn J, Tang, Colin, Vela, Ian, Thomas, Paul, Rutherford, Natalie, Martin, Jarad M, Frydenberg, Mark, Shakher, Ramdave, Wong, Lih-Ming, Taubman, Kim, Ting Lee, Sze, Hsiao, Edward, Roach, Paul, Nottage, Michelle, Kirkwood, Ian, Hayne, Dickon, Link, Emma, Marusic, Petra, Matera, Anetta, Herschtal, Alan, Iravani, Amir, Hicks, Rodney J, Williams, Scott, Murphy, Declan G
• Format: Article
• Language: English
• Subjects: Accuracy; Aged; Antigens; Antigens, Surface - administration & dosage; Antigens, Surface - pharmacology; Biomarkers; Biopsy; Bone imaging; Clinical trials; Computed tomography; Gallium; Glutamate Carboxypeptidase II - administration & dosage; Glutamate Carboxypeptidase II - pharmacology; Health risks; Histopathology; Humans; Lymphatic Metastasis - diagnostic imaging; Lymphatic Metastasis - pathology; Male; Management; Medical imaging; Membranes; Metastases; Metastasis; Middle Aged; Neoplasm Metastasis - diagnostic imaging; Nuclear medicine; Patients; Pelvis; Positron emission; Positron Emission Tomography Computed Tomography - methods; Prospective Studies; Prostate cancer; Prostatic Neoplasms - diagnosis; Prostatic Neoplasms - pathology; Questionnaires; Radiation effects; Radiation therapy; Randomization; Risk; Scanning; Scintigraphy; Sensitivity; Sensitivity and Specificity; Subgroups; Surgery; Tomography; Whole Body Imaging - methods
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(20)30314-7

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. 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. 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