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dc.contributor.authorDearnaley, D
dc.contributor.authorHinder, V
dc.contributor.authorHijab, A
dc.contributor.authorHoran, G
dc.contributor.authorSrihari, N
dc.contributor.authorRich, P
dc.contributor.authorHouston, JG
dc.contributor.authorHenry, AM
dc.contributor.authorGibbs, S
dc.contributor.authorVenkitaraman, R
dc.contributor.authorCruickshank, C
dc.contributor.authorHassan, S
dc.contributor.authorMiners, A
dc.contributor.authorMason, M
dc.contributor.authorPedley, I
dc.contributor.authorPayne, H
dc.contributor.authorBrock, S
dc.contributor.authorWade, R
dc.contributor.authorRobinson, A
dc.contributor.authorDin, O
dc.contributor.authorLees, K
dc.contributor.authorGraham, J
dc.contributor.authorWorlding, J
dc.contributor.authorMurray, J
dc.contributor.authorParker, C
dc.contributor.authorGriffin, C
dc.contributor.authorSohaib, A
dc.contributor.authorHall, E
dc.contributor.authorPROMPTS investigators,
dc.date.accessioned2022-03-23T15:31:58Z
dc.date.available2022-03-23T15:31:58Z
dc.date.issued2022-03-10
dc.identifier.citationThe Lancet. Oncology, 2022
dc.identifier.issn1470-2045
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/5049
dc.identifier.eissn1474-5488
dc.identifier.eissn1474-5488
dc.identifier.doi10.1016/s1470-2045(22)00092-4
dc.identifier.doi10.1016/s1470-2045(22)00092-4
dc.description.abstractBACKGROUND: 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.formatPrint-Electronic
dc.languageeng
dc.language.isoeng
dc.publisherELSEVIER SCIENCE INC
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectPROMPTS investigators
dc.titleObservation 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.typeJournal Article
dcterms.dateAccepted2022-02-10
rioxxterms.versionAM
rioxxterms.versionofrecord10.1016/s1470-2045(22)00092-4
rioxxterms.licenseref.startdate2022-03-10
dc.relation.isPartOfThe Lancet. Oncology
pubs.notesNot 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-statusPublished
pubs.embargo.termsNot known
icr.researchteamClinical Trials & Statistics Unit
dc.contributor.icrauthorDearnaley, David
dc.contributor.icrauthorCruickshank, Clare
dc.contributor.icrauthorGriffin, Clare
dc.contributor.icrauthorHall, Emma


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