The Gleason grading system for prostate cancer (PCa) is based on the proportions of Gleason patterns (GP) 3-5. While pure GP3 has minimal metastatic potential, it is unclear whether GP3 quantity in the presence of GP4 and GP5 affects oncological outcomes.
To assess the predictive value of PCa biopsy GP lengths on long-term metastasis-free survival (MFS).
Prostate biopsies of 1,881 men with screen-detected PCa who participated in the Dutch part of the European Randomized Study of Screening for Prostate Cancer (ERSPC) between 1993 and 2007 were revised for GP 3-5 length. Multivariable Cox regression analyses were used to evaluate the relationship between GP lengths and MFS truncated at 20 years, adjusting for clinical-tumour stage (cT), prostate-specific antigen (PSA), percentage positive biopsies and the presence of invasive cribriform/intraductal carcinoma (CR/IDC).
On multivariable analysis, ≥cT2, PSA, percentage positive cores and absolute length of GP4 and GP5 were all significantly associated with MFS. The discriminative ability was improved by adding CR/IDC to the model. Total GP3 length was neither associated with MFS in the model with (hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.97-1.00, P = 0.3) nor without CR/IDC (HR 0.98, 95% CI 0.96-1.01, P = 0.2). A limitation is the lack of targeted biopsies.
GP3 length does not have an impact on the prediction of MFS in biopsies, once GP4/GP5 lengths are known. Although GP3 percentage is essential in Gleason grading, MFS is related to absolute GP4 and GP5 quantity rather than their proportion to GP3.
Histopathology. 2025 Nov 26 [Epub ahead of print]
Lisa J Kroon, Sebastiaan Remmers, Ivo I de Vos, Charlotte F Kweldam, L Lucia Rijstenberg, Roderick C N van den Bergh, Monique J Roobol, Geert J L H van Leenders
Department of Pathology, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, The Netherlands., Department of Urology, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, The Netherlands., Department of Pathology, Maasstad Hospital, Rotterdam, The Netherlands.