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.
University of Michigan Medical Center, Ann Arbor, Michigan, USA.
Nirav S
NS
Kapadia
Karin
K
Olson
Howard M
HM
Sandler
Felix Y
FY
Feng
Daniel A
DA
Hamstra
D000368:Aged; D015331:Cohort Studies; D039621:Eukaryotic Initiation Factor-3 / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000032:analysis*; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D013997:Time Factors; D017211:Treatment Failure
C105988:EIF3A protein, human; D039621:Eukaryotic Initiation Factor-3; D017430:Prostate-Specific Antigen