Valicenti RK et al. (2006) Posttreatment prostatic-specific antigen doubling times as a surrogate endpoint for prostate cancer-specific survival: an analysis of Radiation Therapy Oncology Group Protocol 92–02. Int J Radiat Oncol Biol Phys 66: 1064–1071

Several large, retrospective databases have shown that short prostate-specific-antigen doubling time (PSADT) can predict prostate-cancer-specific mortality. Pretreatment PSADT predicts treatment failure, while a high pretreatment PSA velocity is associated with an increased risk of death from prostate cancer following radiotherapy. Valicenti et al. used Prentice's Criteria of surrogacy to prospectively evaluate whether post-treatment PSADT could act as a surrogate end point for cause-specific survival (CSS) in men with locally advanced prostate cancer.

Patients were treated on Radiation Therapy Oncology Group (RTOG) Protocol 92–02, consisting of randomization to radiotherapy plus short-term (n = 761) or long-term (n = 753) androgen deprivation. Follow-up was a median of 5.9 years. The long-term regimen was associated with a 43% reduction in prostate-cancer-specific mortality compared with the short-term regimen. Three of the four PSADT thresholds tested could be predicted by the randomized treatment and were predictive of CSS, as required by Prentice's Criteria. Although the fourth threshold, PSADT <3 months, predicted for a poor outcome, it did not meet the surrogacy requirements. Further analysis showed that the effect of PSADT on CSS was not independent of treatment.

PSADT does not, therefore, meet all of the criteria for surrogacy. Valicenti et al. recommend that clinical trials continue to use CSS or absolute survival as primary end points. An established surrogate for CSS would ideally, say the authors, be useful in determining a treatment strategy, as well as in extrapolating data and designing trials.