Interval to biochemical failure as a biomarker for cause-specific and overall survival after dose-escalated external beam radiation therapy for prostate cancer

BACKGROUND: After external beam radiation therapy (EBRT) for prostate cancer, a short interval to biochemical failure of <18 months has been proposed as a surrogate for cause-specific survival. Because EBRT dose influences biochemical failure, the authors investigated the interval to biochemical failure in a cohort of patients treated with dose-escalated EBRT. METHODS: From 1998 to 2008, 710 patients were treated with EBRT (>= 75 grays) +/- androgen deprivation therapy (ADT) at the University of Michigan. Biochemical failure was defined using the Phoenix consensus definition (nadir + 2 ng/ mL). A short interval to biochemical failure was defined as < 18 months after completing radiotherapy and/ or ADT. The associations between biochemical failure, the interval to biochemical failure, and clinical factors with cause-specific survival (CSS) and overall survival (OS) were evaluated. RESULTS: There were 149 biochemical failures (21%), and short interval to biochemical failure accounted for 14% and 40% of biochemical failures in those with intermediate-risk or high-risk disease, respectively. Biochemical failure impacted CSS (P <.0001) but not OS (P.36). However, a short interval to biochemical failure predicted decreased CSS (P <.0001; hazard ratio [HR], 5.6; 95% confidence interval [CI], 2.4-13.0) and OS (P <.0001; HR, 4.8; 95% CI, 2.3-10.3) when compared with a long interval to biochemical failure. The 8-year OS was 78% without biochemical failure, compared with 87% with a long interval to biochemical failure (P.1; HR, 0.7; 95% CI, 0.4-1.1) and 38% with a short interval to biochemical failure (P <.0001; HR, 3.7; 95% CI, 2.3-5.9). On multivariate analysis, a short interval to biochemical failure increased the risk of prostate cancer death (P <.0001; HR, 18.1; 95% CI, 8.4-39) and all cause mortality (P.0027; HR, 1.5; 95% CI, 1.2-2.1), whereas a long interval to biochemical failure did not. CONCLUSIONS: The relation between the interval to biochemical failure, CSS, and OS was independently validated in patients treated with dose-escalated EBRT. Further evaluation of the interval to biochemical failure as a surrogate endpoint is warranted. Cancer 2012; 118: 2059-68. (C) 2011 American Cancer Society.