Reassessing the Evidence: Is Intensified Therapy Justified in Older Patients with Metastatic Hormone-Sensitive Prostate Cancer?

To assess the comparative efficacy of intensified systemic treatments in older patients (≥ 65 years) with metastatic hormone-sensitive prostate cancer (mHSPC) through a network meta-analysis (NMA), and evaluate whether routine use of intensified regimens is justified in this population. A systematic literature search of MEDLINE, Embase, and Cochrane Library databases identified randomized controlled trials published between 2000 and 2024 evaluating first-line systemic therapies in mHSPC. Eligible studies combined androgen deprivation therapy (ADT) with docetaxel, abiraterone, enzalutamide, apalutamide, darolutamide, or antiandrogens. The primary endpoint was overall survival (OS). Bayesian NMA was conducted using a consistency model and Markov chain Monte Carlo simulations. SUCRA values were used to estimate treatment rankings. Subgroup data for older patients were extracted where available. Eleven were included in the analysis. Compared to ADT alone, none of the intensified regimens showed statistically significant superiority in OS in older subgroups. ADT + docetaxel + darolutamide had the highest probability of being the most effective treatment (SUCRA 87.8%), followed by ADT + abiraterone + enzalutamide (SUCRA 80.9%). In older patients with mHSPC, intensified systemic regimens demonstrate trends toward improved OS but fail to achieve clear statistical superiority over ADT alone. The substantial heterogeneity across studies and absence of older-specific subgroup data limit definitive conclusions. Treatment decisions in this population should be individualized using geriatric assessment, considering patient fitness, comorbidities, life expectancy, and treatment goals. Further dedicated trials in older and frail patients are warranted to guide optimal therapeutic strategies.