Risk-adapted durations of hormone therapy combined with radiotherapy for prostate cancer

Combining androgen deprivation therapy (ADT) with definitive radiotherapy improves oncologic outcomes in localized and locally advanced prostate cancer; however, the optimal duration of ADT remains contested. We synthesized evidence from randomized trials, individual patient-level and network meta-analyses, and contemporary guidelines (NCCN 2025; ASTRO/AUA 2024; EAU 2024) to propose a risk-adapted framework. We further evaluated how radiotherapy modality—external-beam radiotherapy (EBRT), brachytherapy boost, proton beam therapy (PBT), and carbon-ion radiotherapy (CIRT)—and toxicity/quality-of-life (QoL) considerations should modulate recommended durations, and we summarize survivorship management. ADT is not indicated for low-risk disease; in favorable intermediate-risk disease, dose-escalated radiotherapy alone or a very short course of ADT (0–4 months) is reasonable. In unfavorable intermediate-risk disease, short-term ADT (4–6 months) improves survival and disease control. For high-risk disease treated with EBRT, long-term ADT (24–36 months) remains standard, although intermediate-term therapy (~18 months) may preserve efficacy with superior QoL in appropriately selected patients. When a brachytherapy boost is added, shorter durations (12–18 months) may suffice without compromising survival. PBT and CIRT generally adhere to the same risk-adapted durations. Systemic intensification with abiraterone (±enzalutamide) improves metastasis-free and overall survival in high-risk, non-metastatic settings. Modern imaging with prostate-specific membrane antigen positron emission tomography refines staging and may support de-escalation in truly localized disease, while emerging digital-pathology artificial intelligence may identify patients who derive benefit from prolonged ADT. Ultimately, ADT duration should be individualized—none for low risk, short term for unfavorable intermediate risk, and long term for high/very high risk—modulated by radiotherapy modality, comorbidity, and QoL. Future trials should validate biomarker- and imaging-guided, response-adaptive duration strategies alongside proactive survivorship care.