Biopsy Gleason pattern 4 burden refines preoperative risk stratification in prostate cancer

To evaluate the prognostic value of biopsy-based Gleason pattern 4 (GP4) burden in a racially and ethnically diverse cohort of men with intermediate- and high-risk prostate cancer undergoing radical prostatectomy.

We retrospectively identified 368 men with biopsy-proven Gleason grade group (GG) 2 to 4 prostate cancer treated with radical prostatectomy (RP) between 2017 and 2024. GP4 burden was quantified using multiple biopsy-based measures. Primary outcomes were adverse surgical pathology (ASP) at prostatectomy-extraprostatic extension, seminal vesicle invasion, or lymph node invasion-and biochemical recurrence (BCR) within 3 years. Associations were evaluated using multivariable regression; model discrimination was assessed using Harrell's concordance index. A point-based pattern 4 risk score (P4RS) was developed and compared with an established preoperative clinical risk nomogram for prediction of early biochemical recurrence.

The cohort was racially and ethnically diverse (76% Black or Hispanic/Latino). ASP occurred in 38% of patients and 17% experienced BCR within 3 years of surgery. ASP risk rose 15% per 2-millimeter increase in total length of pattern 4 on biopsy. Among patients with ≤15 mm GP4, 3-year BCR risk rose 22% per 2-millimeter increase; precision was limited beyond this range. Absolute GP4 metrics improved discrimination for BCR (concordance index 0.716-0.723) relative to GG (0.690). Among risk stratification models, the P4RS demonstrated the highest discrimination (concordance index 0.728).

Absolute Gleason pattern 4 burden, particularly total length, provides clinically meaningful prognostic information beyond grade group and improves risk stratification for adverse pathology and early oncologic outcomes after prostatectomy.