Skip to Main Content
An official website of the United States government
Scheduled Maintenance: CDAS will be undergoing maintenance on Saturday, October 17th from 5:30 AM to 9:30 AM U.S. Eastern Standard Time. During this time you may experience intermittent downtime.

Plasma-Volume–Adjusted PSA Density for Detection of Clinically Significant Prostate Cancer in the PLCO Trial (Original Project: PLCO-2070))

Principal Investigator

Name
Firas Abdollah

Institution
Henry Ford Health

Position Title
Vice-Chair of Academics & Research, Department of Urology/ Clinical associated professor

Email
fabdoll1@hfhs.org

About this CDAS Project

Study
PLCO (Learn more about this study)

Project ID
PLCO-2086

Initial CDAS Request Approval
Oct 5, 2026

Title
Plasma-Volume–Adjusted PSA Density for Detection of Clinically Significant Prostate Cancer in the PLCO Trial (Original Project: PLCO-2070))

Summary
Prostate-specific antigen (PSA) screening can facilitate the early detection of prostate cancer but is limited by imperfect specificity, overdiagnosis, and unnecessary diagnostic procedures. Serum PSA concentration is influenced not only by prostate cancer but also by benign prostate volume, age, and body composition. Conventional PSA density, calculated as serum PSA divided by prostate volume, partially addresses this limitation by accounting for the amount of PSA-producing prostate tissue.
Body mass index (BMI) may independently influence serum PSA concentration. Men with obesity generally have a larger circulating plasma volume, which may lower measured PSA concentration through hemodilution. However, current PSA-based risk-assessment approaches do not account for plasma volume. We propose evaluating a novel metric, PSA mass density (PSA-MD), which adjusts serum PSA for both estimated plasma volume and prostate volume:
Body surface area (m²) = 0.007184 × height (cm)^0.725 × weight (kg)^0.425
Estimated plasma volume (L) = body surface area × 1.670
PSA mass = serum PSA × estimated plasma volume
PSA mass density = PSA mass ÷ prostate volume
The primary objective is to validate PSA-MD and determine whether it improves detection of clinically significant prostate cancer compared with serum PSA and conventional PSA density.
We will conduct a retrospective cohort study using data from the PLCO Cancer Screening Trial. The primary analytic cohort will include participants with an available serum PSA measurement, height and weight, transrectal ultrasound–derived prostate volume, and subsequent diagnostic and cancer outcome information.
Data will be obtained from the PLCO Prostate Person, Prostate Screening, Prostate Diagnostic Procedures, Prostate Treatment, and cancer and mortality follow-up datasets. Variables will include age, race, family history, height, weight, BMI, PSA, digital rectal examination findings, biopsy results, prostate volume, Gleason score or Grade Group (GG), clinical stage, treatment, and cause-specific mortality.
The primary outcome will be clinically-significant prostate cancer, defined as Gleason score ≥7 or GG ≥2. Secondary outcomes will include any prostate cancer, GG ≥3 disease, advanced-stage disease, and prostate cancer–specific mortality (PCSM).
We will first evaluate the relationships among BMI, estimated plasma volume, and serum PSA concentration, including analyses among men without prostate cancer to assess the potential effect of hemodilution independently of malignancy.
The diagnostic performance of PSA-MD will then be compared with serum PSA and conventional PSA density. Discrimination will be evaluated using the area under the receiver-operating characteristic curve, with differences assessed using appropriate paired comparisons. Calibration will be assessed using calibration plots, calibration intercept and slope, and Brier scores. Decision-curve analysis will estimate the potential clinical utility of each measure across relevant biopsy-risk thresholds.
Multivariable logistic regression will evaluate the independent association between PSA-MD and clinically significant prostate cancer after adjustment for age, race, family history, digital rectal examination findings, prior biopsy history, and other available covariates. Performance will also be examined across BMI categories to determine whether PSA-MD provides greater benefit among men with overweight or obesity. Sensitivity analyses will assess alternative definitions of clinically significant disease, including GG ≥3. Cox proportional-hazards and competing-risk regression models may be used to evaluate PCSM.

Aims

The primary objective is to validate PSA-MD and determine whether it improves detection of clinically significant prostate cancer compared with serum PSA and conventional PSA density.
Aim 1: Quantify the association of BMI and estimated plasma volume with serum PSA and determine whether plasma-volume adjustment reduces BMI-related variation in PSA.
Aim 2: Validate PSA mass density—calculated as serum PSA multiplied by estimated plasma volume and divided by prostate volume—and compare its discrimination, calibration, and clinical utility with serum PSA and conventional PSA density for detecting clinically significant prostate cancer.
Aim 3: Determine whether the performance of PSA mass density differs across BMI categories and clinically relevant definitions of aggressive prostate cancer.

Collaborators

Firas Abdollah Henry Ford Health
Mario Tiscione Henry Ford Health
Antonio Cimmino Henry Ford Health
Alex Stephens Henry Ford Health
Akshay Sood James Cancer Hospital and Solove Research Institute
Comprehensive Cancer Center