Refining Risk Stratification of High-risk and Locoregional Prostate Cancer: A Pooled Analysis of Randomized Trials.

Androgen deprivation therapy High-risk prostate cancer Metastasis-free survival Overall survival Radiotherapy Risk stratification

Journal

European urology
ISSN: 1873-7560
Titre abrégé: Eur Urol
Pays: Switzerland
ID NLM: 7512719

Informations de publication

Date de publication:
21 May 2024
Historique:
received: 09 01 2024
revised: 17 04 2024
accepted: 25 04 2024
medline: 23 5 2024
pubmed: 23 5 2024
entrez: 22 5 2024
Statut: aheadofprint

Résumé

Radiotherapy (RT) and long-term androgen deprivation therapy (ltADT; 18-36 mo) is a standard of care in the treatment of high-risk localized/locoregional prostate cancer (HRLPC). We evaluated the outcomes in patients treated with RT + ltADT to identify which patients have poorer prognosis with standard therapy. Individual patient data from patients with HRLPC (as defined by any of the following three risk factors [RFs] in the context of cN0 disease-Gleason score ≥8, cT3-4, and prostate-specific antigen [PSA] >20 ng/ml, or cN1 disease) treated with RT and ltADT in randomized controlled trials collated by the Intermediate Clinical Endpoints in Cancer of the Prostate group. The outcome measures of interest were metastasis-free survival (MFS), overall survival (OS), time to metastasis, and prostate cancer-specific mortality. Multivariable Cox and Fine-Gray regression estimated hazard ratios (HRs) for the three RFs and cN1 disease. A total of 3604 patients from ten trials were evaluated, with a median PSA value of 24 ng/ml. Gleason score ≥8 (MFS HR = 1.45; OS HR = 1.42), cN1 disease (MFS HR = 1.86; OS HR = 1.77), cT3-4 disease (MFS HR = 1.28; OS HR = 1.22), and PSA >20 ng/ml (MFS HR = 1.30; OS HR = 1.21) were associated with poorer outcomes. Adjusted 5-yr MFS rates were 83% and 78%, and 10-yr MFS rates were 63% and 53% for patients with one and two to three RFs, respectively; corresponding 10-yr adjusted OS rates were 67% and 60%, respectively. In cN1 patients, adjusted 5- and 10-yr MFS rates were 67% and 36%, respectively, and 10-yr OS was 47%. HRLPC patients with two to three RFs (and cN0) or cN1 disease had the poorest outcomes on RT and ltADT. This will help in counseling patients treated in routine practice and in guiding adjuvant trials in HRLPC. Radiotherapy and long-term hormone therapy are standard treatments for high-risk and locoregional prostate cancer. In this report, we defined prognostic groups within high-risk/locoregional prostate cancer and showed that outcomes to standard therapy are poorest in those with two or more "high-risk" factors or evidence of lymph node involvement. Such patients may therefore be the best candidates for intensification of treatment.

Sections du résumé

BACKGROUND AND OBJECTIVE OBJECTIVE
Radiotherapy (RT) and long-term androgen deprivation therapy (ltADT; 18-36 mo) is a standard of care in the treatment of high-risk localized/locoregional prostate cancer (HRLPC). We evaluated the outcomes in patients treated with RT + ltADT to identify which patients have poorer prognosis with standard therapy.
METHODS METHODS
Individual patient data from patients with HRLPC (as defined by any of the following three risk factors [RFs] in the context of cN0 disease-Gleason score ≥8, cT3-4, and prostate-specific antigen [PSA] >20 ng/ml, or cN1 disease) treated with RT and ltADT in randomized controlled trials collated by the Intermediate Clinical Endpoints in Cancer of the Prostate group. The outcome measures of interest were metastasis-free survival (MFS), overall survival (OS), time to metastasis, and prostate cancer-specific mortality. Multivariable Cox and Fine-Gray regression estimated hazard ratios (HRs) for the three RFs and cN1 disease.
KEY FINDINGS AND LIMITATIONS UNASSIGNED
A total of 3604 patients from ten trials were evaluated, with a median PSA value of 24 ng/ml. Gleason score ≥8 (MFS HR = 1.45; OS HR = 1.42), cN1 disease (MFS HR = 1.86; OS HR = 1.77), cT3-4 disease (MFS HR = 1.28; OS HR = 1.22), and PSA >20 ng/ml (MFS HR = 1.30; OS HR = 1.21) were associated with poorer outcomes. Adjusted 5-yr MFS rates were 83% and 78%, and 10-yr MFS rates were 63% and 53% for patients with one and two to three RFs, respectively; corresponding 10-yr adjusted OS rates were 67% and 60%, respectively. In cN1 patients, adjusted 5- and 10-yr MFS rates were 67% and 36%, respectively, and 10-yr OS was 47%.
CONCLUSIONS AND CLINICAL IMPLICATIONS CONCLUSIONS
HRLPC patients with two to three RFs (and cN0) or cN1 disease had the poorest outcomes on RT and ltADT. This will help in counseling patients treated in routine practice and in guiding adjuvant trials in HRLPC.
PATIENT SUMMARY RESULTS
Radiotherapy and long-term hormone therapy are standard treatments for high-risk and locoregional prostate cancer. In this report, we defined prognostic groups within high-risk/locoregional prostate cancer and showed that outcomes to standard therapy are poorest in those with two or more "high-risk" factors or evidence of lymph node involvement. Such patients may therefore be the best candidates for intensification of treatment.

Identifiants

pubmed: 38777647
pii: S0302-2838(24)02380-7
doi: 10.1016/j.eururo.2024.04.038
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Auteurs

Praful Ravi (P)

Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: praful_ravi@dfci.harvard.edu.

Wanling Xie (W)

Dana-Farber Cancer Institute, Boston, MA, USA.

Marc Buyse (M)

International Drug Development Institute, Louvain-la-Neuve, Belgium; I-BioStat, Hasselt University, Hasselt, Belgium.

Susan Halabi (S)

Duke University, Durham, NC, USA.

Philip W Kantoff (PW)

Convergent Therapeutics, Cambridge, MA, USA; Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Oliver Sartor (O)

Mayo Clinic, Rochester, MN, USA.

Gert Attard (G)

University College London, London, UK.

Noel Clarke (N)

The Christie NHS Foundation Trust, Manchester, UK.

Anthony D'Amico (A)

Dana-Farber Cancer Institute, Boston, MA, USA; Brigham & Women's Hospital, Boston, MA, USA.

James Dignam (J)

University of Chicago, Chicago, IL, USA.

Nicholas James (N)

The Institute of Cancer Research & The Royal Marsden NHS Foundation Trust, London, UK.

Karim Fizazi (K)

Institut Gustave Roussy, University of Paris Saclay, Villejuif, France.

Silke Gillessen (S)

Oncology Institute of Southern Switzerland, EOC, Bellinzona, Switzerland; Università della Svizzera Italiana, Lugano, Switzerland.

Wendy Parulekar (W)

Queens University, Kingston, Ontario, Canada.

Howard Sandler (H)

Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Daniel E Spratt (DE)

University Hospitals Siedman Cancer Center, Case Western Reserve University, Cleveland, OH, USA.

Matthew R Sydes (MR)

MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK.

Bertrand Tombal (B)

Cliniques Universitaires Saint-Luc, Brussels, Belgium.

Scott Williams (S)

Peter Maccallum Cancer Centre, Melbourne, Australia.

Christopher J Sweeney (CJ)

South Australian Immunogenomics Cancer Institute, University of Adelaide, Adelaide, Australia. Electronic address: christopher.sweeney@adelaide.edu.au.

Classifications MeSH