A 25-YEAR retrospective analysis has raised important questions about the real-world benefit of androgen deprivation therapy (ADT) intensification in patients with advanced prostate cancer.
The study evaluated 160 propensity score-matched patients treated between 2000 and 2019, comparing outcomes between those who received intensified ADT, using androgen receptor signalling inhibitors (ARSIs) and/or chemotherapy, and those treated with conventional combined androgen blockade (CAB) alone. Each group included 80 patients, with comparable baseline characteristics.
Key Findings: Survival Outcomes Compared
Over a median follow-up of 63 months, mortality rates were high across the cohort: 64.4% of patients died from any cause, and nearly half (48.1%) died specifically from prostate cancer. However, the analysis revealed no significant difference in overall survival (OS) between the intensified and conventional treatment groups.
Notably, prostate cancer-specific survival (PCSS) was significantly worse in patients receiving intensified ADT, with a hazard ratio of 1.783. This unexpected finding challenges assumptions drawn from clinical trials and current treatment guidelines, which recommend treatment intensification for advanced disease.
Further multivariable analysis identified elevated baseline lactate dehydrogenase (LDH) levels and a shorter time to progression to castration-resistant prostate cancer (CRPC) as independent predictors of poorer outcomes, affecting both overall and prostate cancer-specific survival. In contrast, treatment intensification itself was not associated with improved survival outcomes.
Implications for Personalised Treatment Strategies
The authors suggest that these findings may reflect underlying tumour biology rather than treatment effects alone. Patients selected for intensified therapy in real-world settings may have more aggressive disease, potentially explaining the observed survival disadvantage.
This study highlights the complexity of translating clinical trial data into routine practice. While ADT intensification remains a cornerstone of guideline-recommended care, these results suggest that its benefits may not be universal and should be considered alongside individual patient risk factors.
The researchers emphasise the need for improved risk stratification tools to better identify which patients are most likely to benefit from intensified treatment strategies. Prospective studies are also needed to validate these findings and refine personalised approaches to advanced prostate cancer management.
Reference
Shimabukuro T et al. Real-World Impact of Androgen Deprivation Therapy Intensification on Prostate Cancer Outcome: A Propensity Score-Matched Analysis From a 25-Year Institutional Experience. Adv Urol. 2026; DOI: 10.1155/aiu/7524312.
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