Quantification of Prostate Cancer Gleason Pattern 4 to Predict Oncological Outcome

Gleason grading remains the cornerstone of prostate cancer risk stratification, yet paradoxes persist. Two men with the same absolute volume of Gleason pattern 4 (GP4) can be assigned to different risk groups depending on the amount of Gleason pattern 3, despite GP3 contributing little prognostic value. Even more paradoxically, a tumor with more GP4 may receive a lower Gleason score if it also contains abundant GP3 (Figure 1). We investigated whether quantifying the absolute burden of GP4 better predicts post-prostatectomy metastasis.

Figure 1: Illustration of Gleason scoring limitations. The left tumor (3+4, ISUP 2) has a higher metastatic risk than the right tumor (4+4, ISUP 4) because of a larger absolute GP4 volume, highlighting the value of quantifying GP4 burden

We analyzed a monocentric cohort of 446 men with ISUP 2–4 prostate cancer containing GP4 but no GP5, treated between 2009 and 2018. GP4 was quantified by three methods: percentage of GP4, length in millimeters, and MRI-derived and targeted biopsy-derived volume. We compared these against established risk tools (Gleason score, CAPRA, STAR-CAP, NCCN, and EAU).

Across all methods, GP4 quantification outperformed Gleason score and established risk scores in predicting recurrence and metastasis. MRI-estimated GP4 volume provided the highest discrimination, with a C-index of 0.80.

Our findings support incorporating GP4 burden—particularly MRI-derived volume—into routine risk stratification, offering a more precise and clinically relevant measure to guide treatment intensification or de-escalation.

Written by: Jonathan Olivier, MD, PhD, Urology Department, Claude Huriez Hospital, CHU Lille, Lille, France.

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