Bone Biomarkers and Subsequent Survival in Men with Hormone-sensitive Prostate Cancer: Results from the SWOG S1216 Phase 3 Trial of Androgen Deprivation Therapy with or Without Orteronel.
Biomarkers
Bone turnover
Hormone sensitive
Overall survival
Predictive
Prognostic
Prostate cancer
Journal
European urology
ISSN: 1873-7560
Titre abrégé: Eur Urol
Pays: Switzerland
ID NLM: 7512719
Informations de publication
Date de publication:
19 Apr 2023
19 Apr 2023
Historique:
received:
26
09
2022
revised:
30
01
2023
accepted:
29
03
2023
pmc-release:
19
10
2024
medline:
22
4
2023
pubmed:
22
4
2023
entrez:
21
04
2023
Statut:
aheadofprint
Résumé
Bone biomarkers are strongly prognostic for overall survival (OS) in men with castration-resistant prostate cancer but not fully established for hormone-sensitive prostate cancer (HSPC). Bone biomarkers in HSPC were prospectively evaluated as part of a phase 3 study of androgen deprivation therapy ± the CYP17 inhibitor orteronel. Patients were randomly divided into training (n = 316) and validation (n = 633) sets. Recursive partitioning and Cox proportional hazard models were employed. Bone resorption (C-telopeptide and pyridinoline) and bone formation markers (C-terminal collagen propeptide and bone alkaline phosphatase) were assessed from patient sera. Of 1279 men, 949 had evaluable baseline bone biomarkers. Optimal cutoffs were identified to define elevated levels of each of the four biomarkers (all p < 0.05) that were associated with worse OS. After adjusting for clinical risk factors in the validation set, elevated bone biomarkers were statistically significantly associated with an increased risk of death (hazard ratios ranging from 1.37 to 1.92). Recursive partitioning algorithms applied to the training set identified three risk groups (low, intermediate, and poor) with differential OS outcomes (median OS: 8.2, 5.1, and 2.1 yr, respectively) based on combinations of bone biomarkers. These results were confirmed in the validation set. In men with HSPC initiating androgen deprivation therapy, bone biomarkers are strongly and independently prognostic for OS. Bone biomarker levels alone or in combination with clinical covariates identify unique subsets of men with differential OS outcomes. These results validate the clinical value of bone biomarker assessment in the HSPC state, extending bone biomarker utility beyond the castration-resistant state. In men with newly diagnosed metastatic prostate cancer, high levels of bone turnover biomarkers are associated with a shorter lifespan.
Sections du résumé
BACKGROUND
BACKGROUND
Bone biomarkers are strongly prognostic for overall survival (OS) in men with castration-resistant prostate cancer but not fully established for hormone-sensitive prostate cancer (HSPC).
OBJECTIVE
OBJECTIVE
Bone biomarkers in HSPC were prospectively evaluated as part of a phase 3 study of androgen deprivation therapy ± the CYP17 inhibitor orteronel.
DESIGN, SETTING, AND PARTICIPANTS
METHODS
Patients were randomly divided into training (n = 316) and validation (n = 633) sets. Recursive partitioning and Cox proportional hazard models were employed.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
METHODS
Bone resorption (C-telopeptide and pyridinoline) and bone formation markers (C-terminal collagen propeptide and bone alkaline phosphatase) were assessed from patient sera.
RESULTS AND LIMITATIONS
CONCLUSIONS
Of 1279 men, 949 had evaluable baseline bone biomarkers. Optimal cutoffs were identified to define elevated levels of each of the four biomarkers (all p < 0.05) that were associated with worse OS. After adjusting for clinical risk factors in the validation set, elevated bone biomarkers were statistically significantly associated with an increased risk of death (hazard ratios ranging from 1.37 to 1.92). Recursive partitioning algorithms applied to the training set identified three risk groups (low, intermediate, and poor) with differential OS outcomes (median OS: 8.2, 5.1, and 2.1 yr, respectively) based on combinations of bone biomarkers. These results were confirmed in the validation set.
CONCLUSIONS
CONCLUSIONS
In men with HSPC initiating androgen deprivation therapy, bone biomarkers are strongly and independently prognostic for OS. Bone biomarker levels alone or in combination with clinical covariates identify unique subsets of men with differential OS outcomes. These results validate the clinical value of bone biomarker assessment in the HSPC state, extending bone biomarker utility beyond the castration-resistant state.
PATIENT SUMMARY
RESULTS
In men with newly diagnosed metastatic prostate cancer, high levels of bone turnover biomarkers are associated with a shorter lifespan.
Identifiants
pubmed: 37085425
pii: S0302-2838(23)02715-X
doi: 10.1016/j.eururo.2023.03.036
pmc: PMC10662935
mid: NIHMS1940614
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : P30 CA093373
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180819
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180888
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA233340
Pays : United States
Informations de copyright
Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.
Références
J Natl Cancer Inst. 2014 Apr;106(4):dju013
pubmed: 24565955
Curr Osteoporos Rep. 2021 Oct;19(5):494-499
pubmed: 34319488
Int J Endocrinol. 2015;2015:838202
pubmed: 25802521
Clin Chem. 2019 Jan;65(1):87-99
pubmed: 30602476
N Engl J Med. 2021 Sep 16;385(12):1091-1103
pubmed: 34161051
Lancet Oncol. 2013 Aug;14(9):893-900
pubmed: 23871417
Cancer Treat Res Commun. 2018;16:18-23
pubmed: 31298998
J Clin Oncol. 2022 Oct 1;40(28):3301-3309
pubmed: 35446628
Eur Urol. 2015 May;67(5):825-36
pubmed: 25097095
Curr Opin Support Palliat Care. 2010 Sep;4(3):127-34
pubmed: 20489645
Cancer Treat Rev. 2006;32 Suppl 1:23-6
pubmed: 16680835
Clin Cancer Res. 2006 Mar 1;12(5):1556-63
pubmed: 16533781
J Clin Oncol. 2014 Apr 10;32(11):1143-50
pubmed: 24590644