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.

Autor:	Dearnaley D; Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK; Urology Unit, Royal Marsden NHS Foundation Trust, London, UK., Hinder V; Clinical Trials and Statistics Unit, The Institute of Cancer Research, London, UK., Hijab A; Urology Unit, Royal Marsden NHS Foundation Trust, London, UK., Horan G; Clinical Oncology, The Queen Elizabeth Hospital King's Lynn NHS Foundation Trust, King's Lynn, UK., Srihari N; Clinical Oncology, The Shrewsbury and Telford Hospital NHS Trust, Shrewsbury, UK., Rich P; Radiology, St George's University Hospitals NHS Foundation Trust, London, UK., Houston JG; Imaging Science and Technology, University of Dundee, Dundee, UK., Henry AM; Clinical Oncology, University of Leeds, Leeds, UK., Gibbs S; Clinical Oncology, Barking, Havering and Redbridge University Hospitals NHS Trust, London, UK., Venkitaraman R; Clinical Oncology, East Suffolk and North Essex NHS Foundation Trust, Ipswich, UK., Cruickshank C; Clinical Trials and Statistics Unit, The Institute of Cancer Research, London, UK., Hassan S; Clinical Trials and Statistics Unit, The Institute of Cancer Research, London, UK., Miners A; Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK., Mason M; Clinical Oncology, Cardiff University, Cardiff, UK., Pedley I; Clinical Oncology, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK., Payne H; Clinical Oncology, University College London Hospitals NHS Foundation Trust, London, UK., Brock S; Clinical Oncology, University Hospitals Dorset NHS Foundation Trust, Poole, UK., Wade R; Clinical Oncology, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK., Robinson A; Clinical Oncology, Brighton and Sussex University Hospitals NHS Trust, Brighton, UK., Din O; Clinical Oncology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK., Lees K; Clinical Oncology, Maidstone and Tunbridge Wells NHS Trust, Maidstone, UK., Graham J; Clinical Oncology, Somerset NHS Foundation Trust, Taunton, UK., Worlding J; Oncology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK., Murray J; Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK; Urology Unit, Royal Marsden NHS Foundation Trust, London, UK., Parker C; Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK; Urology Unit, Royal Marsden NHS Foundation Trust, London, UK., Griffin C; Clinical Trials and Statistics Unit, The Institute of Cancer Research, London, UK., Sohaib A; Urology Unit, Royal Marsden NHS Foundation Trust, London, UK., Hall E; Clinical Trials and Statistics Unit, The Institute of Cancer Research, London, UK. Electronic address: emma.hall@icr.ac.uk.
Jazyk:	angličtina
Zdroj:	The Lancet. Oncology [Lancet Oncol] 2022 Apr; Vol. 23 (4), pp. 501-513. Date of Electronic Publication: 2022 Mar 10.
DOI:	10.1016/S1470-2045(22)00092-4
Abstrakt:	Background: 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. Methods: 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. Findings: 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 scans in the intervention group. As of data cutoff (April 23, 2020), at a median follow-up of 22 months (IQR 13 to 31), time to cSCC was not significantly improved with screening (hazard ratio 0·64 [95% CI 0·37 to 1·11]; Gray's test p=0·12). 1-year cSCC rates were 6·7% (95% CI 3·8-10·6; 14 of 210 patients) for the control group and 4·3% (2·1-7·7; nine of 210 patients) for the intervention group (difference -2·4% [95% CI -4·2 to 0·1]). Median time to cSCC was not reached in either group. No serious adverse events were reported within 24 h of screening. Interpretation: Despite the substantial incidence of rSCC detected in the intervention group, the rate of cSCC in both groups was low at a median of 22 months of follow-up. Routine use of screening MRI and pre-emptive treatment to prevent cSCC is not warranted in patients with asymptomatic castration-resistant prostate cancer with spinal metastasis. Funding: Cancer Research UK. Competing Interests: Declaration of interests EH reports grants from Cancer Research UK, during the conduct of the study and outside of the submitted work; grants and non-financial support from AstraZeneca and Bayer; and grants from Accuray, Varian Medical Systems, Janssen-Cilag, Roche Products, Merck Sharp & Dohme, and Pharma Limited (Sanofi). VH reports grants from Cancer Research UK, during the conduct of the study. GH reports speaker fees from Janssen outside the submitted work. CP reports speaker fees from Bayer and Janssen; advisory board fees from AAA, Clarity Pharmaceuticals, Myovant, ITM Radiopharma, and has an advisory board membership with Janssen and an education steering committee membership with Bayer, outside of the submitted work. DD reports grants from Cancer Research UK, during the conduct of the study; National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) grants; and a patent (EP1933709B1, issued for a localisation and stabilisation device), outside of the submitted work. AS reports NIHR BRC funding to The Royal Marsden Hospital, speaker fees from Pfizer, and being past president and on the executive board for International Cancer Imaging Society (without payment), outside the submitted work. MM reports participation on Data Monitoring Board and Advisory Board for Endocyte and Clovis, outside the submitted work. All other authors declare no competing interests. (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu