Refined Analysis of Prostate-specific Antigen Kinetics to Predict Prostate Cancer Active Surveillance Outcomes

Eur Urol. 2018 Aug;74(2):211-217. doi: 10.1016/j.eururo.2018.01.017. Epub 2018 Feb 9.

Abstract

Background: For men on active surveillance for prostate cancer, utility of prostate-specific antigen (PSA) kinetics (PSAk) in predicting pathologic reclassification remains controversial.

Objective: To develop prediction methods for utilizing serial PSA and evaluate frequency of collection.

Design, setting, and participants: Data were collected from men enrolled in the multicenter Canary Prostate Active Surveillance Study, for whom PSA data were measured and biopsies performed on prespecified schedules. We developed a PSAk parameter based on a linear mixed-effect model (LMEM) that accounted for serial PSA levels.

Outcome measurements and statistical analysis: The association of diagnostic PSA and/or PSAk with time to reclassification (increase in cancer grade and/or volume) was evaluated using multivariable Cox proportional hazards models.

Results and limitations: A total of 851 men met the study criteria; 255 (30%) had a reclassification event within 5 yr. Median follow-up was 3.7 yr. After adjusting for prostate size, time since diagnosis, biopsy parameters, and diagnostic PSA, PSAk was a significant predictor of reclassification (hazard ratio for each 0.10 increase in PSAk=1.6 [95% confidence interval 1.2-2.1, p<0.001]). The PSAk model improved stratification of risk prediction for the top and bottom deciles of risk over a model without PSAk. Model performance was essentially identical using PSA data measured every 6 mo to those measured every 3 mo. The major limitation is the reliability of reclassification as an end point, although it drives most treatment decisions.

Conclusions: PSAk calculated using an LMEM statistically significantly predicts biopsy reclassification. Models that use repeat PSA measurements outperform a model incorporating only diagnostic PSA. Model performance is similar using PSA assessed every 3 or 6 mo. If validated, these results should inform optimal incorporation of PSA trends into active surveillance protocols and risk calculators.

Patient summary: In this report, we looked at whether repeat prostate-specific antigen (PSA) measurements, or PSA kinetics, improve prediction of biopsy outcomes in men using active surveillance to manage localized prostate cancer. We found that in a large multicenter active surveillance cohort, PSA kinetics improves the prediction of surveillance biopsy outcome.

Keywords: Active surveillance; Kinetics; Outcomes; Prostate cancer; Prostate-specific antigen.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Biopsy
  • Clinical Decision-Making
  • Decision Support Techniques*
  • Disease Progression
  • Humans
  • Kallikreins / blood*
  • Kinetics
  • Male
  • Middle Aged
  • Neoplasm Grading
  • North America
  • Predictive Value of Tests
  • Prospective Studies
  • Prostate-Specific Antigen / blood*
  • Prostatic Neoplasms / blood*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / therapy
  • Risk Assessment
  • Risk Factors
  • Tumor Burden
  • Watchful Waiting*

Substances

  • Kallikreins
  • kallikrein-related peptidase 3, human
  • Prostate-Specific Antigen