Efficacy of androgen deprivation therapy (ADT) in combination with radiation therapy, compared to ADT alone in patients with high-risk prostate cancer: an updated systematic review and meta-analysis.

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 study aimed to systematically evaluate the effectiveness of ADT combined with RT versus ADT alone in patients with prostate cancer (clinically node positive, locally advanced disease, metastatic disease), focusing on overall survival (OS), prostate-specific mortality (PSM), progression-free survival (PFS), and the risk of complications. A comprehensive search of PubMed, Embase, Web of Science, and Scopus was conducted between 1st January 2000 and 15th October 2024 to identify studies comparing ADT alone to ADT combined with RT. Hazard ratios (HRs) and relative risks (RRs) with 95% confidence intervals (CIs) were calculated for the outcomes. The certainty of the evidence was assessed using the standard GRADE approach. 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-related complications (RR = 1.10, 95% CI, 1.02, 1.18). The overall certainty of evidence was judged to be 'moderate' for survival outcomes and 'low' for risk of complications. Combining ADT with radiation therapy RT significantly improved survival, compared to ADT alone, especially in patients with locally advanced or node-positive prostate cancer, yet with moderate GRADE certainty. However, this combination also increased the risk of complications. The results advocate that our findings are most applicable to high-risk non-metastatic and cN+ disease and do not support routine addition of RT to ADT in unselected metastatic patients. Therefore, further research is needed to refine treatment protocols and identify the optimal timing and patient subgroups for this approach.