Local Failure and Survival After Definitive Radiotherapy for Aggressive Prostate Cancer: An Individual Patient-level Meta-analysis of Six Randomized Trials.
High grade
Local failure
Radiotherapy
Journal
European urology
ISSN: 1873-7560
Titre abrégé: Eur Urol
Pays: Switzerland
ID NLM: 7512719
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
27
04
2019
accepted:
15
10
2019
pubmed:
14
11
2019
medline:
19
3
2021
entrez:
14
11
2019
Statut:
ppublish
Résumé
The importance of local failure (LF) after treatment of high-grade prostate cancer (PCa) with definitive radiotherapy (RT) remains unknown. To evaluate the clinical implications of LF after definitive RT. Individual patient data meta-analysis of 992 patients (593 Gleason grade group [GG] 4 and 399 GG 5) enrolled in six randomized clinical trials. Multivariable Cox proportional hazard models were developed to evaluate the relationship between overall survival (OS), PCa-specific survival (PCSS), and distant metastasis (DM)-free survival (DMFS) and LF as a time-dependent covariate. Markov proportional hazard models were developed to evaluate the impact of specific transitions between disease states on these endpoints. Median follow-up was 6.4 yr overall and 7.2 yr for surviving patients. LF was significantly associated with OS (hazard ratio [HR] 1.70 [95% confidence interval {CI} 1.37-2.10]), PCSS (3.10 [95% CI 2.33-4.12]), and DMFS (HR 1.92 [95% CI 1.54-2.39]), p < 0.001 for all). Patients who had not transitioned to the LF state had a significantly lower hazard of transitioning to a PCa-specific death state than those who transitioned to the LF state (HR 0.13 [95% CI 0.04-0.41], p < 0.001). Additionally, patients who transitioned to the LF state had a greater hazard of DM or death (HR 2.46 [95% CI 1.22-4.93], p = 0.01) than those who did not. LF is an independent prognosticator of OS, PCSS, and DMFS in high-grade localized PCa and a subset of DM events that are anteceded by LF events. LF events warrant consideration for intervention, potentially suggesting a rationale for upfront treatment intensification. However, whether these findings apply to all men or just those without significant comorbidity remains to be determined. Men who experience a local recurrence of high-grade prostate cancer after receiving upfront radiation therapy are at significantly increased risks of developing metastases and dying of prostate cancer.
Sections du résumé
BACKGROUND
The importance of local failure (LF) after treatment of high-grade prostate cancer (PCa) with definitive radiotherapy (RT) remains unknown.
OBJECTIVE
To evaluate the clinical implications of LF after definitive RT.
DESIGN, SETTING, AND PARTICIPANTS
Individual patient data meta-analysis of 992 patients (593 Gleason grade group [GG] 4 and 399 GG 5) enrolled in six randomized clinical trials.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
Multivariable Cox proportional hazard models were developed to evaluate the relationship between overall survival (OS), PCa-specific survival (PCSS), and distant metastasis (DM)-free survival (DMFS) and LF as a time-dependent covariate. Markov proportional hazard models were developed to evaluate the impact of specific transitions between disease states on these endpoints.
RESULTS AND LIMITATIONS
Median follow-up was 6.4 yr overall and 7.2 yr for surviving patients. LF was significantly associated with OS (hazard ratio [HR] 1.70 [95% confidence interval {CI} 1.37-2.10]), PCSS (3.10 [95% CI 2.33-4.12]), and DMFS (HR 1.92 [95% CI 1.54-2.39]), p < 0.001 for all). Patients who had not transitioned to the LF state had a significantly lower hazard of transitioning to a PCa-specific death state than those who transitioned to the LF state (HR 0.13 [95% CI 0.04-0.41], p < 0.001). Additionally, patients who transitioned to the LF state had a greater hazard of DM or death (HR 2.46 [95% CI 1.22-4.93], p = 0.01) than those who did not.
CONCLUSIONS
LF is an independent prognosticator of OS, PCSS, and DMFS in high-grade localized PCa and a subset of DM events that are anteceded by LF events. LF events warrant consideration for intervention, potentially suggesting a rationale for upfront treatment intensification. However, whether these findings apply to all men or just those without significant comorbidity remains to be determined.
PATIENT SUMMARY
Men who experience a local recurrence of high-grade prostate cancer after receiving upfront radiation therapy are at significantly increased risks of developing metastases and dying of prostate cancer.
Identifiants
pubmed: 31718822
pii: S0302-2838(19)30774-2
doi: 10.1016/j.eururo.2019.10.008
pmc: PMC7008470
mid: NIHMS1549705
pii:
doi:
Types de publication
Journal Article
Meta-Analysis
Langues
eng
Sous-ensembles de citation
IM
Pagination
201-208Subventions
Organisme : NCI NIH HHS
ID : P30 CA016042
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA092131
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180822
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180868
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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