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. 2025 Jun 6.
doi: 10.1007/s00428-025-04117-2. Online ahead of print.

Comparison of highest and overall percentage Gleason pattern 4 in prostate cancer biopsies

L J Kroon  1   2   3 , K P Leeuwenburgh  4   5 , S Remmers  4 , C F Kweldam  5 , R C N van den Bergh  5 , C H Bangma  4   5 , G J L H van Leenders  6 ; Anser Prostate Cancer Network
Affiliations

Comparison of highest and overall percentage Gleason pattern 4 in prostate cancer biopsies

L J Kroon et al. Virchows Arch. .

Abstract

Current guidelines recommend pathologists to report percentage Gleason pattern 4 (GP4%) in Gleason score (GS) 7 prostate cancer (PCa) biopsies. However, it is unspecified whether the highest or overall GP4% should be reported. This study aims to clarify which quantification method correlates best with radical prostatectomy (RP) pathology. This study included 308 men with the highest GS 3 + 4 = 7, 4 + 3 = 7, or 4 + 4 = 8 on centrally revised systematic and/or targeted biopsies who underwent RP between 2018 and 2022. The highest and overall biopsy GP4% were compared with RP GP4% using Spearman's rank correlation coefficient and adverse pathology (AP) (pT-stage ≥ T3, GS ≥ 4 + 3 = 7 and/or pN1) using multivariable logistic regression models adjusted for clinical tumor stage, prostate specific antigen (PSA), percentage of tumor positive biopsies, biopsy modality (systematic/targeted/both), and cribriform pattern. Both quantification methods correlated with RP GP4% (both rho = 0.59), and no significant difference was found between them (p = 0.78). On multivariable analyses, both GP4% quantification methods were significantly associated with AP (per 10% increase, highest GP4% odds ratio [OR] 1.26 [95% CI 1.14-1.39], overall GP4% OR 1.38 [95% CI 1.22-1.58], both p < 0.001). The area under the curve (AUC) was slightly better for overall (0.78 [95% CI 0.73-0.83]) than the highest GP4% (0.76 [95% CI 0.71-0.81], p = 0.041). This study found that the highest and overall biopsy GP4% both correlated with RP GP4%. Although the discriminative performance of the highest and overall GP4% was comparable with respect to AP at RP, the overall GP4% statistically slightly outperformed the highest GP4%. Including the overall GP4% may have added value in risk stratification and clinical decision-making in a subset of PCa patients.

Keywords: Adverse pathology; Carcinoma, Cribriform; Gleason; Prostate biopsy; Prostate cancer; Radical prostatectomy.

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Conflict of interest statement

Declarations. Competing interests: LJK reports that the Jaap Schouten Foundation provided a grant to financially support the PhD work of LJK. The Jaap Schouten Foundation was not involved in the study contents of any kind and also does not have a conflict of interest regarding study contents or results. RCNB reports the following: advisory board (Astellas, Janssen), speaker (Amgen, Astellas, Ipsen, Janssen, MSD), travel grants (Astellas, Bayer), research support (Astellas, Janssen). The other authors have no funding or conflicts of interest to declare.

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