Prostate-specific antigen (PSA) alone is not an appropriate surrogate marker of long-term therapeutic benefit in prostate cancer trials.

The prostate-specific antigen (PSA) is the most studied marker of prostate cancer. It is used for screening and as indicator of disease evolution for individual patients. PSA being a prognostic factor is however not sufficient to justify using PSA-derived endpoints as surrogate for definitive survival endpoint in phase III trials. First, we clarify the terminology and requirements for a marker to be a valid surrogate endpoint. We then review the published literature pertaining to the validation of PSA endpoints as surrogate in all disease stages. We discuss the limitations of these studies and conclude that so far, PSA is not a validated surrogate endpoint in any of the disease settings and treatment conditions considered. We give some recommendations for the planning of trials that would use PSA endpoints (in hormone refractory disease) and for the early stop of (endocrine treatment) trials on the basis of intermediate results based on PSA.