348 Background: Gleason grade group (GG) has traditionally guided prostate cancer risk stratification. Emerging evidence suggests that Gleason pattern 4 (GP4) volume is a better predictor for biochemical recurrence (BCR), metastasis, and mortality. The relationship between biopsy GP4 and clinical outcomes has not been evaluated in high-risk populations but may have significant implications for risk stratification and management of patients across medical, radiation and surgical oncology. Thus, we assessed associations between biopsy GP4 metrics and adverse surgical pathology and BCR in a high-risk and racially diverse cohort. Methods: We retrospectively identified 301 patients who underwent radical prostatectomy (RP) from 2017-2024. Biopsy variables included total cancer length, total GP4 length (GP4-TL, mm), maximum single-core length of GP4 (GP4-MCL), and GP4 percentage (GP4%). Surgical variables included extraprostatic extension (EPE), seminal vesicle invasion (SVI), and highest pathologic GG. BCR rates after RP were also recorded. Patients with incomplete GP4 quantification or GG5 disease at biopsy were excluded. Multivariate logistic regression (adjusted for age and GG) and ROC analyses assessed associations between GP4 metrics and adverse surgical pathology (ASP = EPE/SVI). Kaplan-Meier and Cox proportional hazards models were used to assess the predictive value of GP4 metrics for BCR. Analyses were additionally stratified by race. Results: Among 301 patients (median (IQR) age 62, (57-67)), 42.5% identified as African American/Black, 38.2% as Hispanic/Latino, and 25.2% as White or Other. At biopsy, 72% of patients had GG2, 20% GG3, and 8% GG4 disease. Median (IQR) GP4-TL was 2.7mm (0.80-8.75), GP4-MCL 1.3mm (0.45-3.20), and GP4% 13% (6-34%). At RP, 39% had ASP and 11% were upgraded relative to biopsy Gleason GG. During median 2-year follow-up, 19% of patients developed BCR. In multivariate models, GP4-TL (OR 1.10 per mm, 95% CI 1.06-1.14; p<0.001) and GP4-MCL (OR 1.21 per mm, 95% CI 1.10-1.33; p<0.001) predicted ASP, whereas GP4% did not. GP4-TL remained a strong predictor across all demographic groups (p<0.01), while GP4-MCL was not statistically significant in Black and Hispanic subgroups. GP4-TL also showed the highest discriminative ability versus GG (AUC 0.71 vs 0.56, p<0.001). In survival analysis, 3-year BCR rates increased sharply from 5-10% to over 20% at the GP4-TL ≥ 5 mm threshold, with a hazard ratio of 2.0 compared to patients with < 5 mm GP4-TL. Conclusions: GP4-TL and GP4-MCL independently predicted adverse surgical pathology and BCR, outperforming biopsy GG. Three-year BCR rates rose sharply at GP4-TL ≥ 5 mm, suggesting a clinically relevant threshold. Quantifying GP4 may enhance risk stratification and guide inter-disciplinary decision making among urology, radiologic oncology, and medical oncology teams in the treatment of intermediate- and high-risk prostate cancer.
Karanikolas et al. (Sun,) studied this question.