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Biopsy Gleason Pattern 4 Burden Improves Prediction of Adverse Pathology and 3-Year Biochemical Recurrence After Radical Prostatectomy
Theodoros Karanikolas, BA1, Austin Freedman, BS1, Jonah Tripp, BA, MPH2, Morgan Joseph, BS1, Samuel Yim, MD1, Stephen Reese, MD1, Kara Watts, MD1.
1Montefiore Medical Center & Albert Einstein College of Medicine, Bronx, NY, USA, 2Albert Einstein College of Medicine, Bronx, NY, USA.
BACKGROUND: Recent data suggest biopsy-based absolute Gleason pattern 4 (GP4) burden improves prostate cancer (CaP) risk stratification beyond grade group (GG)-based classifications. We evaluated the prognostic value of GP4 metrics in a racially diverse cohort undergoing radical prostatectomy (RP), focusing on nonlinear risk relationships and integration into preoperative risk models.
METHODS: We retrospectively identified 368 men with biopsy-proven GG2-4 CaP treated with RP (2017-2024). GP4 burden was quantified as total length (LP4) and percent GP4 (GP4%). Primary outcomes were adverse surgical pathology (ASP) at RP and 3-year biochemical recurrence (BCR). Multivariable logistic regression and Cox models adjusted for prostate-specific antigen, clinical stage, and percent positive cores. Restricted cubic splines evaluated nonlinear relationships. A GP4 Risk Score (P4RS) was compared against CaP Risk Assessment (CAPRA) for prediction of 3-year BCR using Harrell's C-index.
RESULTS: The cohort was 76% Black or Hispanic/Latino. ASP occurred in 38% of patients and BCR in 17% within 3 years. LP4 was strongly associated with ASP (OR 2.03 per 10mm; p<0.001) and 3-year BCR (HR 1.40 per 10mm; p<0.001) with greater effect size at lower GP4 burden (HR 2.77 per 10mm at ≤ 15mm LP4). Spline analysis revealed a nonlinear relationship: predicted BCR risk rose 2-4% per mm for LP4 ≤ 5mm, stabilizing to 1% thereafter. LP4 improved discrimination for early BCR in both multivariable models (C-index: GG-based clinical model, 0.690; GP4%-based, 0.702; LP4-based 0.720) and clinical nomograms (C-index: CAPRA, 0.676; P4RS, 0.728).
CONCLUSIONS: Absolute GP4 burden provides clinically meaningful prognostic information beyond ratio-based grading. Its nonlinear impact—particularly at lower volumes—suggests that absolute quantification significantly refines risk stratification for intermediate- and high-risk CaP in diverse populations.
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