Background: Prostate cancer (PCa) is considered one of the most important medical problems in the male population, with a very high incidence after the age of 65. Frailty represents one of the most critical issues facing healthcare due to its inherent relationship with poor healthcare outcomes. The physical phenotype of frailty syndrome based on Fried criteria has been associated with poor outcomes, morbidity, and premature mortality. To date, there are few studies that have analyzed frailty syndrome in patients with localized and advanced (mPCa) disease under androgen-deprivation therapy. Objective: Our goal was to assess whether there are differences in frailty criteria between mPCa and localized PCa. We also evaluated the role of other geriatric variables such as depressive and insomnia symptoms, which are frequently reported in cancer patients. Methods: In this cross-sectional study, frailty syndrome was evaluated in both groups, as well as its possible relationship with cognitive functions, depressive and insomnia symptoms, and other clinical variables related to PCa and its treatment. Frailty was defined on Fried’s criteria: low lean mass, weakness, self-reported exhaustion, low activity level, and slow walking speed; prefrailty was defined as having one or two of those criteria and frailty as having three or more, depressive symptoms were defined by the Yesavage scale, cognitive functions with the Mini-Mental examination test, and insomnia symptoms by the Athens scale and self-reported health status. Results: The prevalence of prefrailty/frailty was slightly higher in mPCa compared to localized PCa (81.5% versus 72.3%, respectively), however by analyzing each of the frailty criteria, two of them were significantly reduced in mPCa compared to localized PCa patients, e.g., gait speed (p= 0.001) and muscle strength (p= 0.04). The reduced gait speed and muscle strength in mPCa were not due to the increased age in mPCa group, or to an increase in comorbidities or shorter time under androgen-deprivation therapy. The symptoms of insomnia were significantly higher in mPCa patients compared to those with localized PCa (p< 0.05) whereas cognitive functions or depressive symptoms were not significantly different between the two groups. Conclusion: Patients with mPCa under androgen-deprivation therapy display higher alterations in gait speed and muscular strength and insomnia symptoms, thus interventions should be aimed to reduce these alterations in order to limit adverse outcomes related to them and to improve quality of life in these patients.