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.
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.
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.
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.
University Hospitals Seidman Cancer Center, Prostate Cancer Foundation, and the American
Society for Radiation Oncology.