Abstract
Stage IV prostate cancer (PCa) refers to a disease that has metastasized beyond the prostate gland to distant sites, such as bones, visceral organs, or non-regional lymph nodes. While early attempts at curative therapy were occasionally made in oligometastatic cases, current guidelines uniformly recommend palliative-intent management once true metastatic spread is confirmed. Over the past decade, treatment paradigms have shifted from androgen deprivation therapy (ADT) monotherapy to earlier intensification with combination regimens including chemo-hormonal therapy and next-generation hormonal agents to improve survival and quality of life (QoL). This narrative review evaluates the comparative effectiveness of ADT, chemotherapy, novel hormonal agents, and palliative radiotherapy in patients with stage IV prostate cancer. A structured literature search of PubMed, Embase, and the Cochrane Library was conducted for English-language studies published between January 2015 and May 2025. Search terms included "stage IV prostate cancer," "metastatic prostate cancer," "androgen deprivation therapy," "docetaxel," "enzalutamide," "abiraterone," "palliative radiotherapy," and "systemic therapy." Eligible studies involved adult male patients with stage IV prostate cancer receiving systemic therapies or radiotherapy; preclinical studies, case reports, and non-metastatic populations were excluded. ADT remains the foundational therapy for metastatic disease. In hormone-sensitive, high-risk patients, combination therapy with agents such as enzalutamide or abiraterone has been shown to significantly improve progression-free survival (PFS) and overall survival (OS). Chemotherapy, particularly docetaxel, provides survival benefits in patients with high-volume metastatic hormone-sensitive disease, as demonstrated in landmark trials. Cabazitaxel, typically used in the castration-resistant setting, offers favorable tolerability compared to docetaxel rechallenge. Among novel hormonal agents, enzalutamide is often preferred in older or comorbid patients due to superior cost-effectiveness and a more favorable metabolic and cardiovascular profile compared to abiraterone. Palliative radiotherapy contributes to symptom control and local disease management, especially when guided by biomarkers such as circulating tumor cells (CTCs). However, variability in study design, patient characteristics, and prior treatments complicates direct comparisons. Managing stage IV prostate cancer requires an individualized, palliative-focused strategy. This review highlights the value of early combination approaches based on disease volume, patient performance status, comorbidities, and personal preferences. ADT remains the therapeutic cornerstone, with systemic intensification and selective radiotherapy offering additive benefits in appropriately chosen patients.