dc.contributor.author | Dearnaley, D | |
dc.contributor.author | Hinder, V | |
dc.contributor.author | Hijab, A | |
dc.contributor.author | Horan, G | |
dc.contributor.author | Srihari, N | |
dc.contributor.author | Rich, P | |
dc.contributor.author | Houston, JG | |
dc.contributor.author | Henry, AM | |
dc.contributor.author | Gibbs, S | |
dc.contributor.author | Venkitaraman, R | |
dc.contributor.author | Cruickshank, C | |
dc.contributor.author | Hassan, S | |
dc.contributor.author | Miners, A | |
dc.contributor.author | Mason, M | |
dc.contributor.author | Pedley, I | |
dc.contributor.author | Payne, H | |
dc.contributor.author | Brock, S | |
dc.contributor.author | Wade, R | |
dc.contributor.author | Robinson, A | |
dc.contributor.author | Din, O | |
dc.contributor.author | Lees, K | |
dc.contributor.author | Graham, J | |
dc.contributor.author | Worlding, J | |
dc.contributor.author | Murray, J | |
dc.contributor.author | Parker, C | |
dc.contributor.author | Griffin, C | |
dc.contributor.author | Sohaib, A | |
dc.contributor.author | Hall, E | |
dc.contributor.author | PROMPTS investigators, | |
dc.date.accessioned | 2022-03-23T15:31:58Z | |
dc.date.available | 2022-03-23T15:31:58Z | |
dc.date.issued | 2022-03-10 | |
dc.identifier.citation | The Lancet. Oncology, 2022 | |
dc.identifier.issn | 1470-2045 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5049 | |
dc.identifier.eissn | 1474-5488 | |
dc.identifier.eissn | 1474-5488 | |
dc.identifier.doi | 10.1016/s1470-2045(22)00092-4 | |
dc.identifier.doi | 10.1016/s1470-2045(22)00092-4 | |
dc.description.abstract | 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. | |
dc.format | Print-Electronic | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | ELSEVIER SCIENCE INC | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | PROMPTS investigators | |
dc.title | 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. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2022-02-10 | |
rioxxterms.version | AM | |
rioxxterms.versionofrecord | 10.1016/s1470-2045(22)00092-4 | |
rioxxterms.licenseref.startdate | 2022-03-10 | |
dc.relation.isPartOf | The Lancet. Oncology | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Trials & Statistics Unit | |
pubs.publication-status | Published | |
pubs.embargo.terms | Not known | |
icr.researchteam | Clinical Trials & Statistics Unit | |
dc.contributor.icrauthor | Dearnaley, David | |
dc.contributor.icrauthor | Cruickshank, Clare | |
dc.contributor.icrauthor | Griffin, Clare | |
dc.contributor.icrauthor | Hall, Emma | |