Definitions of biochemical failure in prostate cancer following radiation therapy.
OBJECTIVE
The American Society for Therapeutic Radiology and Oncology (ASTRO) published a consensus panel definition of biochemical failure following radiation therapy for prostate cancer. In this paper, we develop a series of alternative definitions of biochemical failure. Using data from 688 patients, we evaluated the sensitivity and specificity of the various definitions, with respect to a defined "clinically meaningful" outcome.


METHODS
The ASTRO definition of biochemical failure requires 3 consecutive rises in prostate-specific antigen (PSA). We considered several modifications to the standard definition: to require PSA rises of a certain magnitude, to consider 2 instead of 3 rises, to require the final PSA value to be greater than a fixed cutoff level, and to define biochemical failure based on the slope of PSA over 1, 1.5, or 2 years. A clinically meaningful failure is defined as local recurrence, distant metastases, initiation of unplanned hormonal therapy, unplanned radical prostatectomy, or a PSA > 25 later than 6 months after radiation.


RESULTS
Requiring the final PSA in a series of consecutive rises to be larger than 1.5 ng/mL increased the specificity of biochemical failure. For a fixed specificity, defining biochemical failure based on 2 consecutive rises, or the slope over the last year, could increase the sensitivity by up to approximately 20%, compared to the ASTRO definition. Using a rule based on the slope over the previous year or 2 rises leads to a slightly earlier detection of biochemical failure than does the ASTRO definition. Even with the best rule, only approximately 20% of true failures are biochemically detected more than 1 year before the clinically meaningful event time.


CONCLUSIONS
There is potential for improvement in the ASTRO consensus definition of biochemical failure. Further research is needed, in studies with long follow-up times, to evaluate the relationship between various definitions of biochemical failure and true clinical outcome.
Taylor
J M
JM
Department of Biostatistics, University of Michigan, Ann Arbor, MI 48104, USA. jmgt@umich.edu
Griffith
K A
KA
Sandler
H M
HM
D000230:Adenocarcinoma / Q000097:blood / Q000532:radiotherapy*; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D003131:Combined Modality Therapy / Q000706:statistics & numerical data; D023381:Endpoint Determination; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000097:blood*; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D011237:Predictive Value of Tests; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000532:radiotherapy*; D012372:ROC Curve; D020266:Radiotherapy, Conformal; D016879:Salvage Therapy / Q000706:statistics & numerical data; D012680:Sensitivity and Specificity; D017211:Treatment Failure
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D017430:Prostate-Specific Antigen