Observation versus screening spinal MRI and pre-emptive treatment for spinal cord compression in patients with castration-resistant prostate cancer and spinal metastases in the UK (PROMPTS): an open-label, randomised, controlled, phase 3 trial

• Published in: The lancet oncology 2022-04, Vol.23 (4), p.501-513
• Main Authors: Dearnaley, David, Hinder, Victoria, Hijab, Adham, Horan, Gail, Srihari, Narayanan, Rich, Philip, Houston, J Graeme, Henry, Ann M, Gibbs, Stephanie, Venkitaraman, Ram, Cruickshank, Clare, Hassan, Shama, Miners, Alec, Mason, Malcolm, Pedley, Ian, Payne, Heather, Brock, Susannah, Wade, Robert, Robinson, Angus, Din, Omar, Lees, Kathryn, Graham, John, Worlding, Jane, Murray, Julia, Parker, Chris, Griffin, Clare, Sohaib, Aslam, Hall, Emma
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Adverse events; Aged; Alkaline phosphatase; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Asymptomatic; Back surgery; Cancer research; Castration; Clinical medicine; Compression; Decompression; Early Detection of Cancer; Epidural; Humans; Magnetic Resonance Imaging; Male; Medical research; Metastases; Metastasis; Morbidity; Patients; Prostate cancer; Prostate-specific antigen; Prostatic Neoplasms, Castration-Resistant - drug therapy; Radiation therapy; Spinal cord; Spinal Cord Compression - diagnostic imaging; Spinal Cord Compression - etiology; Spinal Neoplasms - complications; Spinal Neoplasms - diagnostic imaging; State Medicine; Systematic review; United Kingdom - epidemiology
• ISSN: 1470-2045; 1474-5488
• DOI: 10.1016/S1470-2045(22)00092-4

Early diagnosis of malignant spinal cord compression (SCC) is crucial because pretreatment neurological status is the major determinant of outcome. In metastatic castration-resistant prostate cancer, SCC is a clinically significant cause of disease-related morbidity and mortality. We investigated whether screening for SCC with spinal MRI, and pre-emptive treatment if radiological SCC (rSCC) was detected, reduced the incidence of clinical SCC (cSCC) in asymptomatic patients with metastatic castration-resistant prostate cancer and spinal metastasis. We did a parallel-group, open-label, randomised, controlled, phase 3, superiority trial. Patients with metastatic castration-resistant prostate cancer were recruited from 45 National Health Service hospitals in the UK. Eligible patients were aged at least 18 years, with an Eastern Co-operative Oncology Group performance status of 0–2, asymptomatic spinal metastasis, no previous SCC, and no spinal MRI in the past 12 months. Participants were randomly assigned (1:1), using a minimisation algorithm with a random element (balancing factors were treatment centre, alkaline phosphatase [normal vs raised, with the upper limit of normal being defined at each participating laboratory], number of previous systemic treatments [first-line vs second-line or later], previous spinal treatment, and imaging of thorax and abdomen), to no MRI (control group) or screening spinal MRI (intervention group). Serious adverse events were monitored in the 24 h after screening MRI in the intervention group. Participants with screen-detected rSCC were offered pre-emptive treatment (radiotherapy or surgical decompression was recommended per treating physician's recommendation) and 6-monthly spinal MRI. All patients were followed up every 3 months, and then at month 30 and 36. The primary endpoint was time to and incidence of confirmed cSCC in the intention-to-treat population (defined as all patients randomly assigned), with the primary timepoint of interest being 1 year after randomisation. The study is registered with ISRCTN, ISRCTN74112318, and is now complete. Between Feb 26, 2013, and April 25, 2017, 420 patients were randomly assigned to the control (n=210) or screening MRI (n=210) groups. Median age was 74 years (IQR 68 to 79), 222 (53%) of 420 patients had normal alkaline phosphatase, and median prostate-specific antigen concentration was 48 ng/mL (IQR 17 to 162). Screening MRI detected rSCC in 61 (31%) of 200 patients with assessable