Robustness of ProsVue linear slope for prognostic identification of patients at reduced risk for prostate cancer recurrence: Simulation studies on effects of analytical imprecision and sampling time variation.
OBJECTIVE
The ProsVue assay measures serum total prostate-specific antigen (PSA) over three time points post-radical prostatectomy and calculates rate of change expressed as linear slope. Slopes ≤ 2.0 pg/ml/month are associated with reduced risk for prostate cancer recurrence. However, an indicator based on measurement at multiple time points, calculation of slope, and relation of slope to a binary cutoff may be subject to effects of analytical imprecision and sampling time variation. We performed simulation studies to determine the presence and magnitude of such effects.


METHODS
Using data from a two-site precision study and a multicenter clinical trial of 304 men, we performed simulation studies to assess whether analytical imprecision and sampling time variation can drive misclassifications or classification switching of patients with stable disease or recurrence.


RESULTS
Analytical imprecision related to expected PSA values in a stable disease population results in ≤1.2% misclassifications. For populations with recurrent disease, an analysis taking into account correlation between sampling time points demonstrates that classification switching across the 2.0 pg/ml/month cutoff occurs at a rate ≤11%. In the narrow region of overlap between populations, classification switching maximizes at 12.3%. Lastly, sampling time variation across a wide range of scenarios results in 99.7% retention of proper classification for stable disease patients with linear slopes up to the 75th percentile of the distribution.


CONCLUSIONS
These results demonstrate the robustness of the ProsVue assay and the linear slope indicator. Further, these simulation studies provide a potential framework for evaluation of future assays that rely on the rate of change principle.
Vision Biotechnology Consulting, 19833 Fortuna Del Este Road, Escondido, CA 92029, USA. mjsarno@att.net
Mark J
MJ
Sarno
Charles S
CS
Davis
D001800:Blood Specimen Collection; D002986:Clinical Trials as Topic; D003198:Computer Simulation; D003951:Diagnostic Errors; D006801:Humans; D008297:Male; D008954:Models, Biological; D015337:Multicenter Studies as Topic; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000175:diagnosis*; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis*; D015203:Reproducibility of Results
D017430:Prostate-Specific Antigen