Elderly Men with De Novo Metastatic Castration-Sensitive Prostate Cancer: Therapy and Does Comorbidity Matter

<i>Background and Objectives</i>: Prostate cancer (PC) is largely a disease of elderly men, and de novo metastatic presentations are increasingly reported in this population. Yet older patients remain underrepresented in clinical trials, limiting the applicability of guideline-based treatments. Materials and Methods: We retrospectively analyzed 90 patients aged ≥75 years with de novo metastatic castration-sensitive PC (mCSPC) to describe clinical features, treatment patterns, and survival outcomes. <i>Results</i>: Median age was 81 years; high-volume disease and Gleason grade 9-10 tumors predominated. A substantial portion of patients received androgen deprivation therapy (ADT) alone or with bicalutamide despite recommendations for intensified therapy. Enzalutamide was associated with the longest median progression-free survival (PFS, 25.4 months) and overall survival (OS, 30.5 months), though between-group differences were not significant. Castration resistance occurred only in the high-volume group (22.4%). Absence of hypertension was associated with a lower risk of progression (HR 0.46, 95% CI 0.23-0.92, <i>p</i> = 0.028). <i>Conclusions</i>: Elderly patients with de novo mCSPC often have aggressive forms of the disease. Enzalutamide was associated with numerically longer survival compared to other treatments, although the difference was not statistically significant. Additionally, the absence of hypertension appeared to be linked with a lower risk of progression, suggesting that comorbid conditions such as hypertension may influence treatment outcomes in elderly patients.