Posttreatment prostatic-specific antigen doubling time as a surrogate endpoint for prostate cancer-specific survival: An analysis of Radiation Therapy Oncology Group Protocol 92-02

Richard K Valicenti, Michelle DeSilvio, Gerald E. Hanks, Arthur Porter, Harmar Brereton, Seth A. Rosenthal, William U. Shipley, Howard M. Sandler

Research output: Contribution to journalArticle

40 Scopus citations


Purpose: We evaluated whether posttreatment prostatic-specific antigen doubling time (PSADT) was predictive of prostate cancer mortality by testing the Prentice requirements for a surrogate endpoint. Methods and Materials: We analyzed posttreatment PSA measurements in a cohort of 1,514 men with localized prostate cancer (T2c-4 and PSA level <150 ng/mL), treated and monitored prospectively on Radiation Therapy Oncology Group Protocol 92-02. From June 1992 to April 1995, men were randomized to neoadjuvant androgen deprivation and 65-70 Gy of radiation therapy (n = 761), or in combination with 24 months of adjuvant androgen deprivation (n = 753). Using an adjusted Cox proportional hazards model, we tested if PSADT was prognostic and independent of randomized treatment in this cohort. The endpoints were time to PSADT (assuming first-order kinetics for a minimum of 3 rising PSA measurements) and cancer-specific survival (CSS). Results: After a median follow-up time of 5.9 years, randomized treatment was a significant predictor for CSS (pCox = 0.002), PSADT <6 months (pCox < 0.001), PSADT <9 months (pCox < 0.001), and PSADT <12 months (pCox < 0.001) but not for PSADT <3 (pCox = 0.4). The significant posttreatment PSADTs were also significant predictors of CSS (pCox< 0.001). After adjusting for T stage, Gleason score and PSA, all of Prentice's requirements were not met, indicating that the effect of PSADT on CSS was not independent of the randomized treatment. Conclusions: Prostatic specific antigen doubling time is significantly associated with CSS, but did not meet all of Prentice's requirements for a surrogate endpoint of CSS. Thus, the risk of dying of prostate cancer is not fully explained by PSADT.

Original languageEnglish (US)
Pages (from-to)1064-1071
Number of pages8
JournalInternational Journal of Radiation Oncology Biology Physics
Issue number4
StatePublished - Nov 15 2006
Externally publishedYes



  • Mortality
  • Prostate cancer
  • Prostate-specific antigen doubling time
  • Surrogate endpoint

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

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