Outcomes of men aged ≥60 years old with moderately elevated PSA (1–20 ng/mL) in the PLCO cancer screening trial

Principal Investigator

Name
Scott Eggener

Degrees
M.D.

Institution
University of California, Los Angeles

Position Title
Professor & Department Chair

Email
seggener@mednet.ucla.edu

About this CDAS Project

Study
PLCO (Learn more about this study)

Project ID
PLCO-2084

Initial CDAS Request Approval
Oct 5, 2026

Title
Outcomes of men aged ≥60 years old with moderately elevated PSA (1–20 ng/mL) in the PLCO cancer screening trial

Summary
The purpose of this study is to characterize prostate cancer incidence, metastatic progression, and survival outcomes among men aged ≥60 years with moderately elevated PSA levels (1–20 ng/mL), and to identify subgroups at clinically meaningful risk of adverse prostate cancer outcomes. By leveraging longitudinal data from the Prostate, Lung, Colorectal and Ovarian cancer (PLCO) screening trial, this study aims to inform clinical decision-making regarding the need for further diagnostic evaluation, including prostate MRI and/or prostate biopsy, in men aged > 60 with elevated PSA values.

The study population will include eligible participants from both the PLCO screening (intervention) and usual care (control) arms. Inclusion criteria are age ≥60 years, a first PSA measurement between 1 and 20 ng/mL obtained at age ≥60 years, and no prior prostate cancer diagnosis. Participants with PSA values >20 ng/mL, a prior history of prostate cancer, or missing key outcome data will be excluded. Cohort entry will be defined as the date of the first qualifying PSA measurement.

The primary outcome is prostate cancer-specific mortality. Secondary outcomes include diagnosis of clinically significant prostate cancer (Grade Group ≥2 or Gleason score ≥7), metastasis-free survival, initiation of androgen deprivation therapy, and overall survival.

Baseline characteristics will be described using descriptive statistics. Cumulative incidence methods and competing-risk analyses will be used to evaluate prostate cancer-specific mortality, prostate cancer diagnosis, and metastatic disease. Kaplan-Meier methods and Cox proportional hazards models will assess survival outcomes, while Fine and Gray regression models will evaluate associations between PSA levels and prostate cancer-specific mortality accounting for competing mortality risks. Sensitivity analyses will be conducted separately within the screening and usual care arms. This study will provide evidence-based risk estimates to support individualized decision-making for older men with elevated PSA levels.

Aims

The overall objective of this study is to characterize long-term prostate cancer outcomes among men aged ≥60 years with moderately elevated prostate-specific antigen (PSA) levels (1–20 ng/mL) in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and to identify subgroups at clinically meaningful risk of adverse prostate cancer outcomes.

Aim 1: To characterize the long-term risk of prostate cancer-specific mortality (PCSM) among men aged ≥60 years with PSA levels of 1–20 ng/mL. We will estimate PCSM while accounting for death from other causes as a competing event and evaluate how risk varies according to age, PSA level, PSA kinetics, and other available demographic and clinical characteristics.

Aim 2: To evaluate the long-term incidence of clinically significant prostate cancer (Grade Group ≥2/Gleason score ≥7), distant metastasis, initiation of androgen deprivation therapy (ADT), and all-cause mortality in this population. We will characterize the timing and cumulative incidence of these outcomes following cohort entry.

Aim 3: To identify clinical and PSA-based factors associated with adverse long-term prostate cancer outcomes and determine whether clinically relevant subgroups can be distinguished according to their risk of PCSM, clinically significant prostate cancer, metastatic progression, and competing mortality.

By defining the long-term outcomes of older men across a range of moderately elevated PSA values, this study seeks to provide evidence that may improve risk stratification and inform contemporary decisions regarding further diagnostic evaluation, including prostate MRI and/or prostate biopsy.

Collaborators

Scott Eggener University of California, Los Angeles
MEAGAN SUEN University of California, Los Angeles
Lorna Kwan University of California, Los Angeles
Mehrnaz Siavoshi University of California, Los Angeles
Sarah Connor University of California, Los Angeles