Efficacy of Androgen Deprivation Therapy (ADT) in Combination with Radiation Therapy, compared to ADT alone in Patients with High-Risk Prostate Cancer: a meta-analysis

Abstract Background Androgen deprivation therapy (ADT) has long been a cornerstone of treatment for patients with locally advanced or metastatic hormone-sensitive prostate cancer. The efficacy of ADT plus radiotherapy (RT) compared to ADT alone remains unclear due to conflicting results in existing literature. The aim of the study is to systematically evaluate the effectiveness of ADT combined with RT versus ADT alone in patients with prostate cancer (clinically node positive, locally advancer disease, metastatic disease), focusing on overall survival (OS), prostate-specific mortality (PSM), progression-free survival (PFS), and the risk of complications. Methods A comprehensive search of PubMed, Embase, Web of Science and Scopus, between 1st January 2000 and 15th October 2024, was done to identify studies comparing ADT alone to ADT in combination with RT. Hazard ratios (HR) and relative risk (RR) with 95% confidence intervals (CI) were calculated for the outcomes. The certainty of the evidence was assessed using the standard GRADE approach. Results A total of 8 studies met the inclusion criteria (6 RCTs and 2 cohort studies). These studies included 18,456 patients. The combination of ADT and RT significantly improved OS (HR = 0.75, 95% CI: 0.63, 0.90), PFS (HR = 0.41, 95% CI: 0.20, 0.84), and reduced PSM (HR = 0.52, 95% CI: 0.34, 0.78) compared to ADT alone. Subgroup analysis showed greater OS (HR 0.66, 95% CI: 0.59, 0.75) and PSM (HR 0.43, 95% CI: 0.39, 0.49) in patients with locally advanced or node-positive disease. ADT + RT was also associated with increased risks of genitourinary (RR = 1.80, 95% CI: 1.15, 2.82), gastrointestinal (RR = 4.18, 95% CI: 1.46, 11.96), and sexual dysfunction (RR = 1.10, 95% CI: 1.02, 1.18) related complications. The overall certainty of evidence was judged to be “moderate” for survival outcomes and “Low” for risk of complications. Conclusion Combining ADT with radiation therapy RT significantly improves survival, compared to ADT alone, especially in patients with locally advanced or node-positive prostate cancer. However, this combination also increases the risk of complications. Further research is needed to refine treatment protocols and identify the optimal timing and patient subgroups for this approach.