Date of Award

January 2026

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Michael S. Leapman

Abstract

Background: Active surveillance (AS) is the preferred management strategy for men with favorable-risk prostate cancer, aiming to avoid overtreatment while preserving oncologic safety. However, a meaningful proportion of patients experience Gleason Grade Group (GG) upgrading during follow-up, reflecting either biological progression or baseline misclassification. Multiparametric prostate magnetic resonance imaging (MRI), interpreted using the Prostate Imaging–Reporting and Data System (PI-RADS), is well established for detecting clinically significant prostate cancer at diagnosis, yet its prognostic role during AS remains incompletely defined. Specifically, whether baseline PI-RADS scores independently predict the risk of GG upgrading among men managed with AS has not been systematically quantified across existing studies.

Research Aims: The primary aim of this study was to systematically evaluate and quantify the association between baseline prostate MRI PI-RADS score and the risk of Gleason Grade Group upgrading among patients undergoing active surveillance for prostate cancer. The study also aimed to narratively review the MRI PI-RADS classification as a predictor of clinical endpoints, including metastasis-free survival and treatment.

Hypothesis: We hypothesized that higher baseline PI-RADS scores on prostate MRI are independently associated with an increased risk of Gleason Grade Group upgrading during active surveillance

Methods: We systematically searched eight databases to identify studies evaluating the association between baseline PI-RADS score and the risk of GG upgrade in patients managed with AS for PCa (PROSPERO: CRD42024567762). We pooled the hazard ratios (HR) using Hartung-Knapp random-effects meta-analysis models. We assessed the risk of bias using the ROBINS-I tool.

Results: We included eleven studies (n = 6309) in the meta-analysis. The risk of bias was moderate, attributed to the retrospective and unblinded design of seven included studies. Among studies reporting baseline PI-RADS, 2,640 patients (52.1%) had PI-RADS 1–3 lesions, and 2,421 patients (47.9%) had PI-RADS 4–5 lesions. Baseline PI-RADS 4-5 was associated with an increased risk of upgrade compared to those with PI-RADS 1-3 lesions (HR:2.21, 95%CI: 1.66-2.93, p<.001). Compared to PI-RADS 1-2, the presence of PI-RADS 3 (HR:1.88, 95%CI: 1.29–2.74, p=.008), PI-RADS 4 (HR:2.73, 95%CI: 2.08-3.58, p<.001), or PI-RADS 5 (HR:3.69, 95%CI: 2.50-5.45, p<.001) lesions were associated with an increased risk of upgrade.

Statement of Scientific Impact: Baseline prostate MRI finding as assessed with PI-RADS is highly prognostic for GG upgrading among patients with favorable risk PCa managed with AS. These findings support further study of tailored surveillance strategies based on initial MRI findings.

Comments

This is an Open Access Thesis.

Download
Open Access

This Article is Open Access

Share

COinS