Abstract 3741: Improving Gleason scoring in prostate cancer: Development and clinical value of the Molecular Integrative Quantitative Gleason (MIQ-Gleason)

Abstract We have recently shown that quantification of Gleason 4 patterns (Q-Gleason) provides strong prognostic information beyond traditional Gleason grade groups (3+3, 3+4, 4+3, 8, 9-10) in prostate cancer, and that the prognostic power of Q-Gleason scoring can be further improved if Gleason 5 patterns are integrated to build the Integrative Quantitative Gleason (IQ-Gleason) score, a continuous value ranging from 0 – 117.5. The current study was undertaken, to determine whether (and how) factoring in molecular markers could further improve the predictive power. We selected deletions of PTEN and 6q (by FISH analysis) as well as DNA ploidy information obtained by flow cytometry as examples for established molecular prognostic markers that provided strong and independent prognostic information in our study cohort of more than 17,000 prostate cancers. A “molecular score” was established for these markers including “penalty” points for presence of deletions/aneuploidy and “bonus” points for lack of deletions/diploid DNA status. Penalty and bonus points were separately determined for each parameter based on differences in the recurrence rate between cancers with and without deletions or aneuploidy. The “penalty” points were then added to the IQ-Gleason score points while the “bonus” points were subtracted from the IQ-Gleason in order to obtain the MiQ-Gleason score. The MiQ-Gleason provided strong prognostic information in univariate analysis (p<0.0001) and in multivariate models including PSA level, pT / pN stage, and status of the resection margin. Comparison of Reciever Operator characteristics (ROS) between the MiQ-Gleason and the quantitative Gleason or classical Gleason revealed only a slight increase of the prognostic power for the MiQ-Gleason (AUC=0.781) as compared to the IQ-Gleason (AUC=0.771), while a massive difference was found as compared to the classical Gleason grade groups (AUC=0.719). In summary, our data demonstrate the power of quantitative Gleason scoring strategies as compared to classical Gleason grade groups. That adding selected molecular features improved predicitive power only slightly demonstrates how difficult it is for molecular markers to compete with optimized morphological grading systems. However, the use of more and better molecular testing may provide further improvement beyond quantitative Gleason scoring. Citation Format: Ronald Simon, Martina Kluth, Maximilian Lennartz, Claudia Hube-Magg, Sarah Minner, Maria Christina Tsourlakis, Stefan Steurer, Markus Graefen, Hartwig Huland, Lars Budäus, Guido Sauter, Thorsten Schlomm. Improving Gleason scoring in prostate cancer: Development and clinical value of the Molecular Integrative Quantitative Gleason (MIQ-Gleason) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3741. doi:10.1158/1538-7445.AM2017-3741