Poor agreement of prostate specific antigen doubling times calculated using ultrasensitive versus standard prostate specific antigen values: important impact on risk assessment.
OBJECTIVE
In men with biochemical recurrence after radical prostatectomy, a rapid prostate specific antigen doubling time is associated with adverse outcomes, and is often used to guide the type and timing of salvage therapy. It is unknown whether prostate specific antigen doubling time calculated in the ultrasensitive range (prostate specific antigen less than 0.2 ng/ml) accurately reflects measures performed in the traditional range (prostate specific antigen greater than 0.2 ng/ml).


METHODS
We studied 394 men in a national disease registry of men with prostate cancer (CaPSURE™) who underwent radical prostatectomy, experienced biochemical failure, and had prostate specific antigen doubling time assessed using ultrasensitive and traditional prostate specific antigen values. Agreement between these measurements was assessed using Cohen's kappa score.


RESULTS
Median ultrasensitive prostate specific antigen doubling time was 11.9 months (IQR 6-29) and median traditional prostate specific antigen doubling time was 240 months (IQR 18-240). Agreement between ultrasensitive and traditional prostate specific antigen doubling time was poor, with a weighted Cohen's kappa score of 0.04 (95% CI -0.02-0.10). Using a dichotomous prostate specific antigen doubling time cutoff of 9 months, there was a statistically significant difference between ultrasensitive and standard prostate specific antigen doubling time (exact McNemar p <0.01). Ultrasensitive prostate specific antigen doubling time was more or less rapid than traditional prostate specific antigen doubling time by more than 15 months in 244 (62%) and 35 (9%) patients, respectively.


CONCLUSIONS
Agreement between prostate specific antigen doubling time calculated using ultrasensitive vs traditional prostate specific antigen values is poor. Ultrasensitive prostate specific antigen doubling time is often significantly more rapid than traditional prostate specific antigen doubling time, potentially overestimating the risk of clinical recurrence. Until the significance of ultrasensitive prostate specific antigen doubling time is better characterized, the decision to proceed with salvage therapy should not be based on prostate specific antigen doubling time calculated using ultrasensitive prostate specific antigen values.
Department of Urology, UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California 94115, USA.
Adam C
AC
Reese
Vincent
V
Fradet
Jared M
JM
Whitson
Cole B
CB
Davis
Peter R
PR
Carroll
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood*; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood* / Q000601:surgery; D015203:Reproducibility of Results; D018570:Risk Assessment; D013997:Time Factors
D014408:Biomarkers, Tumor; D017430:Prostate-Specific Antigen