TY - JOUR
T1 - Androgen deprivation therapy use and duration with definitive radiotherapy for localised prostate cancer
T2 - an individual patient data meta-analysis
AU - Kishan, Amar U.
AU - Sun, Yilun
AU - Hartman, Holly
AU - Pisansky, Thomas M.
AU - Bolla, Michel
AU - Neven, Anouk
AU - Steigler, Allison
AU - Denham, James W.
AU - Feng, Felix Y.
AU - Zapatero, Almudena
AU - Armstrong, John G.
AU - Nabid, Abdenour
AU - Carrier, Nathalie
AU - Souhami, Luis
AU - Dunne, Mary T.
AU - Efstathiou, Jason A.
AU - Sandler, Howard M.
AU - Guerrero, Araceli
AU - Joseph, David
AU - Maingon, Philippe
AU - de Reijke, Theo M.
AU - Maldonado, Xavier
AU - Ma, Ting Martin
AU - Romero, Tahmineh
AU - Wang, Xiaoyan
AU - Rettig, Matthew B.
AU - Reiter, Robert E.
AU - Zaorsky, Nicholas G.
AU - Steinberg, Michael L.
AU - Nickols, Nicholas G.
AU - Jia, Angela Y.
AU - MARCAP Consortium group
AU - Garcia, Jorge A.
AU - Spratt, Daniel E.
N1 - Funding Information:
The MARCAP Consortium was developed using funding support from the Prostate Cancer Foundation, the American Society for Radiation Oncology, the University Hospital Seidman Cancer Center, the Jonsson Comprehensive Cancer Center, the Bershad Family Trust, and the Desilva Family Trust. We are grateful to the trial teams, support staff, and patients enrolled in these clinical trials.
Funding Information:
AUK reports personal fees from Varian Medical Systems, ViewRay, and Intelligent Automation; and research support from ViewRay, the American Society for Radiation Oncology, the Prostate Cancer Foundation, and the Jonsson Comprehensive Cancer Center, all outside the submitted work. FYF reports a consulting or advisory role for Astellas, Bayer, BlueEarth Diagnostics, Celgene, EMD Serono, Genentech, Janssen, Myovant, Ryovant, Bristol Myers Squibb, Exact Sciences, Varian, Bluestar Genomics, and Serimmun; and research funding from Zenth Epigenetics. AN reports personal fees from AstraZeneca, outside the submitted work. LS reports personal fees from Sanofi Canada and Varian Medical Systems, outside the submitted work. JAE reports personal fees from Blue Earth, Boston Scientific, AstraZeneca, Taris Biomedical, Merck, Roviant Pharma, and Myovant Sciences. HMS is a member of a clinical trial steering committee for Janssen and reports stock from Radiogel for an inactive role on medical advisory board, all outside of the submitted work. MBR reports personal fees from Amgen, Clovis, Janssen, Bayer, and Abrx; and research support from Janssen and Merck, outside the submitted work. NGN reports research funding from Janssen, Lantheus, and Bayer; and consulting fees from Oncolinea. DES declares personal fees from Janssen, AstraZeneca, and BlueEarth, outside of the submitted work. All other authors declare no competing interests.
Publisher Copyright:
© 2022 Elsevier Ltd
PY - 2022/2/1
Y1 - 2022/2/1
N2 - Background: Randomised trials have investigated various androgen deprivation therapy (ADT) intensification strategies in men receiving radiotherapy for the treatment of prostate cancer. This individual patient data meta-analysis of relevant randomised trials aimed to quantify the benefit of these interventions in aggregate and in clinically relevant subgroups. Methods: For this meta-analysis, we performed a systematic literature search in MEDLINE, Embase, trial registries, the Web of Science, Scopus, and conference proceedings to identify trials with results published in English between Jan 1, 1962, and Dec 30, 2020. Multicentre randomised trials were eligible if they evaluated the use or prolongation of ADT (or both) in men with localised prostate cancer receiving definitive radiotherapy, reported or collected distant metastasis and survival data, and used ADT for a protocol-defined finite duration. The Meta-Analysis of Randomized trials in Cancer of the Prostate (MARCAP) Consortium was accessed to obtain individual patient data from randomised trials. The primary outcome was metastasis-free survival. Hazard ratios (HRs) were obtained through stratified Cox models for ADT use (radiotherapy alone vs radiotherapy plus ADT), neoadjuvant ADT extension (ie, extension of total ADT duration in the neoadjuvant setting from 3–4 months to 6–9 months), and adjuvant ADT prolongation (ie, prolongation of total ADT duration in the adjuvant setting from 4–6 months to 18–36 months). Formal interaction tests between interventions and metastasis-free survival were done for prespecified subgroups defined by age, National Comprehensive Cancer Network (NCCN) risk group, and radiotherapy dose. This meta-analysis is registered with PROSPERO, CRD42021236855. Findings: Our search returned 12 eligible trials that provided individual patient data (10 853 patients) with a median follow-up of 11·4 years (IQR 9·0–15·0). The addition of ADT to radiotherapy significantly improved metastasis-free survival (HR 0·83 [95% CI 0·77–0·89], p<0·0001), as did adjuvant ADT prolongation (0·84 [0·78–0·91], p<0·0001), but neoadjuvant ADT extension did not (0·95 [0·83–1·09], p=0·50). Treatment effects were similar irrespective of radiotherapy dose, patient age, or NCCN risk group. Interpretation: Our findings provide the strongest level of evidence so far to the magnitude of the benefit of ADT treatment intensification with radiotherapy for men with localised prostate cancer. Adding ADT and prolonging the portion of ADT that follows radiotherapy is associated with improved metastasis-free survival in men, regardless of risk group, age, and radiotherapy dose delivered; however, the magnitude of the benefit could vary and shared decision making with patients is recommended. Funding: University Hospitals Seidman Cancer Center, Prostate Cancer Foundation, and the American Society for Radiation Oncology.
AB - Background: Randomised trials have investigated various androgen deprivation therapy (ADT) intensification strategies in men receiving radiotherapy for the treatment of prostate cancer. This individual patient data meta-analysis of relevant randomised trials aimed to quantify the benefit of these interventions in aggregate and in clinically relevant subgroups. Methods: For this meta-analysis, we performed a systematic literature search in MEDLINE, Embase, trial registries, the Web of Science, Scopus, and conference proceedings to identify trials with results published in English between Jan 1, 1962, and Dec 30, 2020. Multicentre randomised trials were eligible if they evaluated the use or prolongation of ADT (or both) in men with localised prostate cancer receiving definitive radiotherapy, reported or collected distant metastasis and survival data, and used ADT for a protocol-defined finite duration. The Meta-Analysis of Randomized trials in Cancer of the Prostate (MARCAP) Consortium was accessed to obtain individual patient data from randomised trials. The primary outcome was metastasis-free survival. Hazard ratios (HRs) were obtained through stratified Cox models for ADT use (radiotherapy alone vs radiotherapy plus ADT), neoadjuvant ADT extension (ie, extension of total ADT duration in the neoadjuvant setting from 3–4 months to 6–9 months), and adjuvant ADT prolongation (ie, prolongation of total ADT duration in the adjuvant setting from 4–6 months to 18–36 months). Formal interaction tests between interventions and metastasis-free survival were done for prespecified subgroups defined by age, National Comprehensive Cancer Network (NCCN) risk group, and radiotherapy dose. This meta-analysis is registered with PROSPERO, CRD42021236855. Findings: Our search returned 12 eligible trials that provided individual patient data (10 853 patients) with a median follow-up of 11·4 years (IQR 9·0–15·0). The addition of ADT to radiotherapy significantly improved metastasis-free survival (HR 0·83 [95% CI 0·77–0·89], p<0·0001), as did adjuvant ADT prolongation (0·84 [0·78–0·91], p<0·0001), but neoadjuvant ADT extension did not (0·95 [0·83–1·09], p=0·50). Treatment effects were similar irrespective of radiotherapy dose, patient age, or NCCN risk group. Interpretation: Our findings provide the strongest level of evidence so far to the magnitude of the benefit of ADT treatment intensification with radiotherapy for men with localised prostate cancer. Adding ADT and prolonging the portion of ADT that follows radiotherapy is associated with improved metastasis-free survival in men, regardless of risk group, age, and radiotherapy dose delivered; however, the magnitude of the benefit could vary and shared decision making with patients is recommended. Funding: University Hospitals Seidman Cancer Center, Prostate Cancer Foundation, and the American Society for Radiation Oncology.
UR - https://www.scopus.com/pages/publications/85123753916
U2 - 10.1016/S1470-2045(21)00705-1
DO - 10.1016/S1470-2045(21)00705-1
M3 - Article
C2 - 35051385
SN - 1470-2045
VL - 23
SP - 304
EP - 316
JO - The Lancet Oncology
JF - The Lancet Oncology
IS - 2
ER -
SDG 3 Good Health and Well-being