Abstract
Abstract Adjuvant therapy for endometrial cancer (EC) is recommended based on risk factors. In current clinical practice these are mainly based on classical pathological factors such as stage, grade and presence of LVSI. The Cancer Genome Atlas Group demonstrated that EC can be divided in four distinct subgroups with impact on prognosis. This has now been shown to be feasible using surrogate markers in multiple large cohorts. Analysis of the intratumoral immune infiltrate using a machine learning image-based algorithm, found that low intraepithelial density of CD8+ cells was an independent prognostic factor for recurrence free survival. Combining intraepithelial CD8+ cell density with molecular and pathological factors improved the risk stratification model. Exploratory analysis found a significant impact within the p53abnormal and no specific molecular profile subgroups. While in intermediate to high-intermediate risk the majority has no specific molecular profile, in high risk there are more patients with POLE hypermutated tumors, p53abnormal and mismatch repair deficient tumors. The question is how to bring these molecular factors to the clinic? Molecular stratification does present additional subgroups with a rationale for targeted approaches. It does however present a challenge for trial design and feasibility, An overview of current ongoing studies using targeted therapies is provided, with a focus on immune checkpoint inhibition. Citation Format: Remi A. Nout. Challenges for future adjuvant studies and the role of immunotherapy in endometrial cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference: Endometrial Cancer: New Biology Driving Research and Treatment; 2020 Nov 9-10. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(3_Suppl):Abstract nr IA004.
Published Version
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