Radiation therapy dose and androgen deprivation therapy in localized prostate cancer: a meta-regression of 5-year outcomes in phase III randomized controlled trials.

Androgen Antagonists / therapeutic use Androgens / therapeutic use Clinical Trials, Phase III as Topic Hormone Replacement Therapy Humans Male Prostatic Neoplasms / drug therapy Randomized Controlled Trials as Topic

Journal

Prostate cancer and prostatic diseases
ISSN: 1476-5608
Titre abrégé: Prostate Cancer Prostatic Dis
Pays: England
ID NLM: 9815755

Informations de publication

Date de publication:
03 2022
Historique:
received: 26 04 2021
accepted: 20 07 2021
revised: 02 07 2021
pubmed: 18 8 2021
medline: 22 4 2022
entrez: 17 8 2021
Statut: ppublish

Résumé

While multiple randomized trials have evaluated the benefit of radiation therapy (RT) dose escalation and the use and prolongation of androgen deprivation therapy (ADT) in the treatment of prostate cancer, few studies have evaluated the relative benefit of either form of treatment intensification with each other. Many trials have included treatment strategies that incorporate either high or low dose RT, or short-term or long-term ADT (STADT or LTADT), in one or more trial arms. We sought to compare different forms of treatment intensification of RT in the context of localized prostate cancer. Using preferred reporting items for systemic reviews and meta-analyses (PRISMA) guidelines, we collected over 40 phases III clinical trials comparing different forms of RT for localized prostate cancer. We performed a meta-regression of 40 individual trials with 21,429 total patients to allow a comparison of the rates and cumulative proportions of 5-year overall survival (OS), prostate cancer-specific mortality (PCSM), and distant metastasis (DM) for each treatment arm of every trial. Dose-escalation either in the absence or presence of STADT failed to significantly improve any 5-year outcome. In contrast, adding LTADT to low dose RT significantly improved 5-year PCSM (Odds ratio [OR] 0.34, 95% confidence interval [CI] 0.22-0.54, p < 0.001) and DM (OR 0.35, 95% CI 0.20-0.63. p < 0.001) over low dose RT alone. Adding STADT also significantly improved 5-year PCSM over low dose RT alone (OR 0.55, 95% CI 0.41-0.75, p < 0.001). While limited by between-study heterogeneity and a lack of individual patient data, this meta-analysis suggests that adding ADT, versus increasing RT dose alone, offers a more consistent improvement in clinical endpoints.

Sections du résumé

BACKGROUND
While multiple randomized trials have evaluated the benefit of radiation therapy (RT) dose escalation and the use and prolongation of androgen deprivation therapy (ADT) in the treatment of prostate cancer, few studies have evaluated the relative benefit of either form of treatment intensification with each other. Many trials have included treatment strategies that incorporate either high or low dose RT, or short-term or long-term ADT (STADT or LTADT), in one or more trial arms. We sought to compare different forms of treatment intensification of RT in the context of localized prostate cancer.
METHODS
Using preferred reporting items for systemic reviews and meta-analyses (PRISMA) guidelines, we collected over 40 phases III clinical trials comparing different forms of RT for localized prostate cancer. We performed a meta-regression of 40 individual trials with 21,429 total patients to allow a comparison of the rates and cumulative proportions of 5-year overall survival (OS), prostate cancer-specific mortality (PCSM), and distant metastasis (DM) for each treatment arm of every trial.
RESULTS
Dose-escalation either in the absence or presence of STADT failed to significantly improve any 5-year outcome. In contrast, adding LTADT to low dose RT significantly improved 5-year PCSM (Odds ratio [OR] 0.34, 95% confidence interval [CI] 0.22-0.54, p < 0.001) and DM (OR 0.35, 95% CI 0.20-0.63. p < 0.001) over low dose RT alone. Adding STADT also significantly improved 5-year PCSM over low dose RT alone (OR 0.55, 95% CI 0.41-0.75, p < 0.001).
CONCLUSION
While limited by between-study heterogeneity and a lack of individual patient data, this meta-analysis suggests that adding ADT, versus increasing RT dose alone, offers a more consistent improvement in clinical endpoints.

Identifiants

DOI: 10.1038/s41391-021-00432-2 PMID: 34400799 PMC: PMC9018418
pubmed: 34400799
doi: 10.1038/s41391-021-00432-2
pii: 10.1038/s41391-021-00432-2
pmc: PMC9018418
doi:

Substances chimiques

Androgen Antagonists 0
Androgens 0

Types de publication

Journal Article Meta-Analysis

Langues

eng

Sous-ensembles de citation

IM

Pagination

126-128

Subventions

Organisme : NCI NIH HHS
ID : P30 CA016042
Pays : United States

Informations de copyright

© 2021. The Author(s).

Références

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Nguyen PL. Optimization of the radiation management of high-risk prostate cancer. Semin Radiat Oncol. 2017;27:43–9.
doi: 10.1016/j.semradonc.2016.08.009 pubmed: 27986211
Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097.
doi: 10.1371/journal.pmed.1000097 pubmed: 19621072 pmcid: 2707599
Trinquart L, Jacot J, Conner SC, Porcher R. Comparison of treatment effects measured by the hazard ratio and by the ratio of restricted mean survival times in oncology randomized controlled trials. J Clin Oncol. 2016;34:1813–9.
doi: 10.1200/JCO.2015.64.2488 pubmed: 26884584
DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.
doi: 10.1016/0197-2456(86)90046-2 pubmed: 3802833
Mottet N, Bellmunt J, Bolla M, Briers E, Cumberbatch MG, De Santis M, et al. EAU-ESTRO-SIOG guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent. Eur Urol. 2017;71:618–29.
doi: 10.1016/j.eururo.2016.08.003 pubmed: 27568654
Polkinghorn WR, Parker JS, Lee MX, Kass EM, Spratt DE, Iaquinta PJ, et al. Androgen receptor signaling regulates DNA repair in prostate cancers. Cancer Discov. 2013;3:1245–53.
doi: 10.1158/2159-8290.CD-13-0172 pubmed: 24027196 pmcid: 3888815
Kishan AU, Chu FI, King CR, Seiferheld W, Spratt DE, Tran P, et al. Local failure and survival after definitive radiotherapy for aggressive prostate cancer: an individual patient-level meta-analysis of six randomized trials. Eur Urol. 2020;77:201–8.
doi: 10.1016/j.eururo.2019.10.008 pubmed: 31718822

Auteurs

Tommy Jiang (T)

Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
ORCID: 0000-0002-1199-0615

Daniela Markovic (D)

Department of Medicine, Statistics Core, University of California, Los Angeles, CA, USA.

Jay Patel (J)

Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.

Jesus E Juarez (JE)

Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.

Ting Martin Ma (TM)

Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.

David Shabsovich (D)

Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.

Nicholas G Nickols (NG)

Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.

Robert E Reiter (RE)

Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.

David Elashoff (D)

Department of Medicine, Statistics Core, University of California, Los Angeles, CA, USA.

Matthew B Rettig (MB)

Division of Hematology and Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Division of Hematology and Oncology, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.

Nicholas G Zaorsky (NG)

Department of Radiation Oncology, Penn State Cancer Institute, Hershey, PA, USA.

Daniel E Spratt (DE)

Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
ORCID: 0000-0002-5973-4741

Amar U Kishan (AU)

Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. aukishan@mednet.ucla.edu.
Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. aukishan@mednet.ucla.edu.
ORCID: 0000-0002-7437-6591

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questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Hormones, substituts d'hormones et antagonistes d'hormones › Antihormones › Antagonistes des androgènes › Radiation therapy dose and androgen...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Hormones, substituts d'hormones et antagonistes d'hormones › Hormones › Androgènes › Radiation therapy dose and androgen...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études cliniques comme sujet › Essais cliniques comme sujet › Essais cliniques de phase III comme sujet › Radiation therapy dose and androgen...
questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Hormonothérapie substitutive › Radiation therapy dose and androgen...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Radiation therapy dose and androgen...
questionsmedicales.fr › Maladies urogénitales › Tumeurs de l'appareil urogénital › Tumeurs de l'appareil génital mâle › Tumeurs de la prostate › Radiation therapy dose and androgen...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études cliniques comme sujet › Essais cliniques comme sujet › Essais cliniques contrôlés comme sujet › Essais contrôlés randomisés comme sujet › Radiation therapy dose and androgen...