Despite therapeutic advances, prostate cancer remains lethal for most patients. Accelerated development of novel therapies requires validated surrogate endpoints to circumvent prolonged survival follow-up in phase III trials. This review systematically evaluates intermediate clinical endpoints (ICEs) in prostate cancer to establish methodologically robust alternatives to overall survival (OS). We first synthesized methodological standards for ICE validation. Subsequent analysis encompassed phase III trials (PubMed/Web of Science, Jan. 2025) in metastatic castration-sensitive (mCSPC) and -resistant prostate cancer (mCRPC), requiring: randomization, therapeutic intervention, OS as primary/co-primary endpoint, ≥1 ICE (radiographic progression-free survival (rPFS), milestone survival), and ≥70 participants. Surrogacy was quantified via two-stage meta-analysis, with R2 ≥ 0.7 defining validity. Metastasis-free survival (MFS) is validated for localized disease, enabling trial endpoint substitution. In advanced stages, evidence for ICEs remains critically deficient. Our analysis identifies milestone survival as a promising ICE candidate in mCSPC and mCRPC, demonstrating strong trial-level correlation with OS. Current ICE validation in prostate cancer is disproportionately focused on localized disease, leaving advanced-stage therapeutic development constrained. While milestone survival shows surrogacy potential, endpoint validation remains methodologically challenging even in rigorously designed trials. This work underscores the imperative to accelerate ICE standardization through unified methodological frameworks and collaborative cross-trial analyses.Copyright © 2025 Elsevier Ltd. All rights reserved.