Rethinking Gleason pattern quantification in predicting metastasis: results of 20 years of follow‐up in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer

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INTRODUCTION: 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. OBJECTIVE: To assess the predictive value of PCa biopsy GP lengths on long-term metastasis-free survival (MFS). METHODS: 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). RESULTS AND LIMITATIONS: 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. CONCLUSION AND CLINICAL IMPLICATIONS: 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.

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