OBJECTIVES: In clinical trials of early-stage prostate cancer, demonstration of an overall survival (OS) benefit is challenging because of prolonged patient survival. While the development of metastasis is a major milestone in the disease, payers are interested in understanding the clinical relevance of metastatic-free survival (MFS) as a surrogate endpoint and its relationship with long-term outcomes, in particular, OS. The objective of the current study was to identify empirical evidence evaluating MFS in patients with prostate cancer. METHODS: A structured literature review was conducted in PubMed (1999−2014) to identify clinical trials in prostate cancer using MFS as a primary endpoint, and clinical and observational studies that evaluated the association between MFS and OS. RESULTS: Three published clinical trials used MFS as a primary endpoint. The studies employed varying definitions for MFS (e.g., bone metastasis only or bone and soft tissue metastasis). In one long-term study comparing adjuvant radiotherapy to usual care, both MFS and OS outcomes were significantly improved with radiotherapy, suggesting a relationship between these two endpoints.  Four additional studies examined the association between MFS and OS. One study reported that distant metastasis at three years met the Prentice criteria for surrogacy of prostate cancer-specific survival at 10 years. A second study reported that MFS was one of four independent prognostic variables for OS in prostate cancer. The remaining two studies demonstrated that time to metastasis was significantly associated with prostate cancer-specific mortality. CONCLUSIONS: MFS has been used as the primary endpoint in several prostate cancer studies, providing support for the clinical relevance of this outcome. Current evidence from the literature suggests an association between MFS and OS, however additional research is needed to further investigate this relationship.