Real‐World Impact of Androgen Deprivation Therapy Intensification on Prostate Cancer Outcome: A Propensity Score‐Matched Analysis From a 25‐Year Institutional Experience

Background and Objective Androgen deprivation therapy (ADT) intensification with androgen receptor signaling inhibitors (ARSIs) and/or chemotherapy is recommended in current guidelines for patients with advanced prostate cancer (PCa). However, its real‐world application and effectiveness remain insufficiently understood. This study reevaluated 25 years of institutional experience with hormonal therapy and compared long‐term oncological outcomes between traditional ADT and intensified ADT strategies. Methods We retrospectively analyzed 160 propensity score‐matched patients selected from a cohort of 352 men who received hormonal therapy between 2000 and 2019. Eighty patients underwent treatment intensification with ARSIs and/or chemotherapy (Intensity group), while 80 received conventional combined androgen blockade (CAB) therapy alone (nonintensity group). Long‐term oncological outcomes were compared between the two groups. Results The median ages were 73 years in the intensity group and 74 years in the nonintensity group. During a median follow‐up of 63 months, 103 patients (64.4%) died from any cause, and 77 (48.1%) died from PCa. Overall survival (OS) did not differ significantly between the two groups, whereas prostate cancer‐specific survival (PCSS) was significantly poorer in the Intensity group (hazard ratio, 1.783; 95% confidence interval, 1.110–2.864; p = 0.017). Multivariable analyses identified higher baseline lactate dehydrogenase (LDH) levels and shorter time to castration‐resistant prostate cancer (CRPC) as independent predictors of both worse OS and worse PCSS. Conclusions This long‐term retrospective study provides important real‐world evidence regarding outcomes of hormonal therapy across different therapeutic eras. Higher baseline LDH levels and shorter time to CRPC—but not ADT intensification—were independently associated with worse OS and PCSS, suggesting the influence of underlying biological and metabolic tumor characteristics. These findings underscore the need for refined risk stratification and prospective studies to optimize individualized treatment approaches, including the appropriate use of ADT intensification.