Prostate specific antigen volatility and the diagnosis of clinically significant prostate cancer
Principal Investigator
Name
John Leppert
Degrees
MD MS
Institution
Stanford University
Position Title
Professor
Email
About this CDAS Project
Study
PLCO
(Learn more about this study)
Project ID
PLCO-1034
Initial CDAS Request Approval
Aug 29, 2022
Title
Prostate specific antigen volatility and the diagnosis of clinically significant prostate cancer
Summary
The prostate specific antigen (PSA) is integral to efforts to screen for prostate cancer, the most common cancer diagnosed in men. However, in men with a modestly elevated PSA, it can be difficult to distinguish prostate cancer from benign conditions, such as benign prostatic hypertrophy, that can also lead to elevations in the PSA measurements. Fluctuations in PSA measurements are frequently encountered during routine prostate cancer screening and determining which men should undergo a prostate biopsy is a clinical challenge. Moreover, systematic screening of men for prostate cancer can lead to the overdiagnosis of indolent prostate cancer that is unlikely to threaten their health.
Guidelines support multiple approaches to improve PSA-based prostate cancer screening with the goal of increasing our ability to identify men most likely to harbor clinically significant prostate cancer, while avoiding overdiagnosis. Soon after PSA was discovered, it became clear that men with prostate cancer were more likely to experience rising PSA levels compared with men with benign prostatic hypertrophy. Subsequent models used in the detection of prostate cancer and in risk stratification have been improved by including more than one PSA measurement and examining how PSA measurements change over time (e.g. PSA velocity).
We hypothesize that increasing PSA variability – the change between screening PSA measurements – is inversely associated with clinically significant prostate cancer and that quantifying the variability in subsequent PSA measurements might help identify men with clinically significant prostate cancer.
Guidelines support multiple approaches to improve PSA-based prostate cancer screening with the goal of increasing our ability to identify men most likely to harbor clinically significant prostate cancer, while avoiding overdiagnosis. Soon after PSA was discovered, it became clear that men with prostate cancer were more likely to experience rising PSA levels compared with men with benign prostatic hypertrophy. Subsequent models used in the detection of prostate cancer and in risk stratification have been improved by including more than one PSA measurement and examining how PSA measurements change over time (e.g. PSA velocity).
We hypothesize that increasing PSA variability – the change between screening PSA measurements – is inversely associated with clinically significant prostate cancer and that quantifying the variability in subsequent PSA measurements might help identify men with clinically significant prostate cancer.
Aims
- determine the amount of PSA variability among a cohort undergoing PSA based prostate cancer screening.
- determine if PSA variability is independently associated with a diagnosis of prostate cancer, and with clinically significant prostate cancer
- determine the performance of measures of PSA variability in specific patient cohorts based on age, race/ethnicity, other comorbidity.
Collaborators
Priyadip Ray, PhD - Lawrence Livermore National Laboratory
James Brooks, MD - Stanford University