Show simple item record

dc.contributor.authorMa, TM
dc.contributor.authorChu, F-I
dc.contributor.authorSandler, H
dc.contributor.authorFeng, FY
dc.contributor.authorEfstathiou, JA
dc.contributor.authorJones, CU
dc.contributor.authorRoach, M
dc.contributor.authorRosenthal, SA
dc.contributor.authorPisansky, T
dc.contributor.authorMichalski, JM
dc.contributor.authorBolla, M
dc.contributor.authorde Reijke, TM
dc.contributor.authorMaingon, P
dc.contributor.authorNeven, A
dc.contributor.authorDenham, J
dc.contributor.authorSteigler, A
dc.contributor.authorJoseph, D
dc.contributor.authorNabid, A
dc.contributor.authorSouhami, L
dc.contributor.authorCarrier, N
dc.contributor.authorIncrocci, L
dc.contributor.authorHeemsbergen, W
dc.contributor.authorPos, FJ
dc.contributor.authorSydes, MR
dc.contributor.authorDearnaley, DP
dc.contributor.authorTree, AC
dc.contributor.authorSyndikus, I
dc.contributor.authorHall, E
dc.contributor.authorCruickshank, C
dc.contributor.authorMalone, S
dc.contributor.authorRoy, S
dc.contributor.authorSun, Y
dc.contributor.authorZaorsky, NG
dc.contributor.authorNickols, NG
dc.contributor.authorReiter, RE
dc.contributor.authorRettig, MB
dc.contributor.authorSteinberg, ML
dc.contributor.authorReddy, VK
dc.contributor.authorXiang, M
dc.contributor.authorRomero, T
dc.contributor.authorSpratt, DE
dc.contributor.authorKishan, AU
dc.contributor.authorMeta-analysis of Randomized trials in Cancer of the Prostate MARCAP Consortium investigators,
dc.identifier.citationEuropean Urology, 2022, 82 (5), pp. S0302-2838(22)02523-4 -
dc.description.abstractCONTEXT: The prognostic importance of local failure after definitive radiotherapy (RT) in National Comprehensive Cancer Network intermediate- and high-risk prostate cancer (PCa) patients remains unclear. OBJECTIVE: To evaluate the prognostic impact of local failure and the kinetics of distant metastasis following RT. EVIDENCE ACQUISITION: A pooled analysis was performed on individual patient data of 12 533 PCa (6288 high-risk and 6245 intermediate-risk) patients enrolled in 18 randomized trials (conducted between 1985 and 2015) within the Meta-analysis of Randomized Trials in Cancer of the Prostate Consortium. Multivariable Cox proportional hazard (PH) models were developed to evaluate the relationship between overall survival (OS), PCa-specific survival (PCSS), distant metastasis-free survival (DMFS), and local failure as a time-dependent covariate. Markov PH models were developed to evaluate the impact of specific transition states. EVIDENCE SYNTHESIS: The median follow-up was 11 yr. There were 795 (13%) local failure events and 1288 (21%) distant metastases for high-risk patients and 449 (7.2%) and 451 (7.2%) for intermediate-risk patients, respectively. For both groups, 81% of distant metastases developed from a clinically relapse-free state (cRF state). Local failure was significantly associated with OS (hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.06-1.30), PCSS (HR 2.02, 95% CI 1.75-2.33), and DMFS (HR 1.94, 95% CI 1.75-2.15, p < 0.01 for all) in high-risk patients. Local failure was also significantly associated with DMFS (HR 1.57, 95% CI 1.36-1.81) but not with OS in intermediate-risk patients. Patients without local failure had a significantly lower HR of transitioning to a PCa-specific death state than those who had local failure (HR 0.32, 95% CI 0.21-0.50, p < 0.001). At later time points, more distant metastases emerged after a local failure event for both groups. CONCLUSIONS: Local failure is an independent prognosticator of OS, PCSS, and DMFS in high-risk and of DMFS in intermediate-risk PCa. Distant metastasis predominantly developed from the cRF state, underscoring the importance of addressing occult microscopic disease. However a "second wave" of distant metastases occurs subsequent to local failure events, and optimization of local control may reduce the risk of distant metastasis. PATIENT SUMMARY: Among men receiving definitive radiation therapy for high- and intermediate-risk prostate cancer, about 10% experience local recurrence, and they are at significantly increased risks of further disease progression. About 80% of patients who develop distant metastasis do not have a detectable local recurrence preceding it.
dc.format.extentS0302-2838(22)02523-4 -
dc.relation.ispartofEuropean Urology
dc.subjectDistant metastasis
dc.subjectLocal control
dc.subjectLocal failure
dc.subjectPooled analysis
dc.subjectProstate cancer
dc.subjectRadiation therapy
dc.titleLocal Failure Events in Prostate Cancer Treated with Radiotherapy: A Pooled Analysis of 18 Randomized Trials from the Meta-analysis of Randomized Trials in Cancer of the Prostate Consortium (LEVIATHAN).
dc.typeJournal Article
rioxxterms.typeJournal Article/Review
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.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Clinical Academic Radiotherapy (Dearnaley)
pubs.publication-statusPublished online
icr.researchteamClinic Acad RT Dearnaley
icr.researchteamClin Trials & Stats Unit
dc.contributor.icrauthorDearnaley, David
dc.contributor.icrauthorHall, Emma
dc.contributor.icrauthorCruickshank, Clare
icr.provenanceDeposited by Mr Arek Surman on 2022-10-18. Deposit type is initial. No. of files: 1. Files: 1-s2.0-S0302283822025234-main.pdf

Files in this item


This item appears in the following collection(s)

Show simple item record
Except where otherwise noted, this item's license is described as