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Local 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)

Authors :
Ma, Ting Martin
Chu, Fang I.
Sandler, Howard
Feng, Felix Y.
Efstathiou, Jason A.
Jones, Christopher U.
Roach, Mack
Rosenthal, Seth A.
Pisansky, Thomas
Michalski, Jeff M.
Bolla, Michel
de Reijke, Theo M.
Maingon, Philippe
Neven, Anouk
Denham, James
Steigler, Allison
Joseph, David
Nabid, Abdenour
Souhami, Luis
Carrier, Nathalie
Incrocci, Luca
Heemsbergen, Wilma
Pos, Floris J.
Sydes, Matthew R.
Dearnaley, David P.
Tree, Alison C.
Syndikus, Isabel
Hall, Emma
Cruickshank, Clare
Malone, Shawn
Roy, Soumyajit
Sun, Yilun
Zaorsky, Nicholas G.
Nickols, Nicholas G.
Reiter, Robert E.
Rettig, Matthew B.
Steinberg, Michael L.
Reddy, Vishruth K.
Xiang, Michael
Romero, Tahmineh
Spratt, Daniel E.
Kishan, Amar U.
Ma, Ting Martin
Chu, Fang I.
Sandler, Howard
Feng, Felix Y.
Efstathiou, Jason A.
Jones, Christopher U.
Roach, Mack
Rosenthal, Seth A.
Pisansky, Thomas
Michalski, Jeff M.
Bolla, Michel
de Reijke, Theo M.
Maingon, Philippe
Neven, Anouk
Denham, James
Steigler, Allison
Joseph, David
Nabid, Abdenour
Souhami, Luis
Carrier, Nathalie
Incrocci, Luca
Heemsbergen, Wilma
Pos, Floris J.
Sydes, Matthew R.
Dearnaley, David P.
Tree, Alison C.
Syndikus, Isabel
Hall, Emma
Cruickshank, Clare
Malone, Shawn
Roy, Soumyajit
Sun, Yilun
Zaorsky, Nicholas G.
Nickols, Nicholas G.
Reiter, Robert E.
Rettig, Matthew B.
Steinberg, Michael L.
Reddy, Vishruth K.
Xiang, Michael
Romero, Tahmineh
Spratt, Daniel E.
Kishan, Amar U.
Source :
Meta-Analysis of Randomized Trials in Cancer of the Prostate (MARCAP) Consortium Investigators , Ma , T M , Chu , F I , Sandler , H , Feng , F Y , Efstathiou , J A , Jones , C U , Roach , M , Rosenthal , S A , Pisansky , T , Michalski , J M , Bolla , M , de Reijke , T M , Maingon , P , Neven , A , Denham , J , Steigler , A , Joseph , D , Nabid , A , Souhami , L , Carrier , N , Incrocci , L , Heemsbergen , W , Pos , F J , Sydes , M R , Dearnaley , D P , Tree , A C , Syndikus , I , Hall , E , Cruickshank , C , Malone , S , Roy , S , Sun , Y , Zaorsky , N G , Nickols , N G , Reiter , R E , Rettig , M B , Steinberg , M L , Reddy , V K , Xiang , M , Romero , T , Spratt , D E & Kishan , A U 2022 , ' Local 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) ' , European Urology , vol. 82 , no. 5 , pp. 487-498 .
Publication Year :
2022

Abstract

Context: 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

Details

Database :
OAIster
Journal :
Meta-Analysis of Randomized Trials in Cancer of the Prostate (MARCAP) Consortium Investigators , Ma , T M , Chu , F I , Sandler , H , Feng , F Y , Efstathiou , J A , Jones , C U , Roach , M , Rosenthal , S A , Pisansky , T , Michalski , J M , Bolla , M , de Reijke , T M , Maingon , P , Neven , A , Denham , J , Steigler , A , Joseph , D , Nabid , A , Souhami , L , Carrier , N , Incrocci , L , Heemsbergen , W , Pos , F J , Sydes , M R , Dearnaley , D P , Tree , A C , Syndikus , I , Hall , E , Cruickshank , C , Malone , S , Roy , S , Sun , Y , Zaorsky , N G , Nickols , N G , Reiter , R E , Rettig , M B , Steinberg , M L , Reddy , V K , Xiang , M , Romero , T , Spratt , D E & Kishan , A U 2022 , ' Local 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) ' , European Urology , vol. 82 , no. 5 , pp. 487-498 .
Notes :
application/pdf, English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1352447588
Document Type :
Electronic Resource