Surrogate End Point for Prostate Cancer-Specific Mortality After Radical Prostatectomy or Radiation Therapy

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Abstract
Background: The relationship between prostate-specific antigen (PSA)–defined recurrence and prostate cancer–specific mortality remains unclear. Therefore, we evaluated the hypothesis that a short post-treatment PSA doubling time (PSA-DT) after radiation therapy is a surrogate end point for prostate cancer–specific mortality by analyzing two multi-institutional databases. Methods: Baseline, treatment, and follow-up information was compiled on a cohort of 8669 patients with prostate cancer treated with surgery (5918 men) or radiation (2751 men) from January 1, 1988, through January 1, 2002, for localized or locally advanced, non-metastatic prostate cancer. We used a Cox regression analysis to test whether the post-treatment PSA-DT was a prognostic factor that was independent of treatment received. All statistical tests were two-sided. Results: The post-treatment PSA-DT was statistically significantly associated with time to prostate cancer–specific mortality and with time to all-cause mortality (all PCox<.001). However, the treatment received was not statistically significantly associated with time to prostate cancer–specific mortality after PSA-defined disease recurrence for patients with a PSA-DT of less than 3 months (PCox = .90) and for patients with a PSA-DT of 3 months or more (PCox = .28) when controlling for the specific value of the PSA-DT. Furthermore, after a PSA-defined recurrence, a PSA-DT of less than 3 months was statistically significantly associated with time to prostate cancer–specific mortality (median time = 6 years; hazard ratio = 19.6, 95% confidence interval = 12.5 to 30.9). Conclusion: A post-treatment PSA-DT of less than 3 months and the specific value of the post-treatment PSA-DT when it is 3 months or more appear to be surrogate end points for prostate cancer–specific mortality after surgery or radiation therapy. We recommend that consideration be given to initiating androgen suppression therapy at the time of a PSA-defined recurrence when the PSA-DT is less than 3 months to delay the imminent onset of metastatic bone disease.