790P - Uniform prospective molecular analysis of endometrial carcinoma: Feasibility, outcomes, and effect on management

Background

Endometrial carcinoma (EC) guidelines (NCCN, ESGO) suggest molecular analysis (MA) for incorporation into risk criteria. Prognostic value of TCGA-based classification has been validated, but adoption into adjuvant treatment decisions is still under evaluation. Examples of real-world upfront MA analysis in EC are scarce. We aim to evaluate our routine implementation of Next Generation Sequencing (NGS) of EC patients.

Methods

In November 2020, we implemented routine immunohistochemistry (IHC) (p53, MMR) & NGS for TCGA-based prognostication of all EC primary resections at a single institution. NGS was a 69 gene panel including POLE, TP53, PTEN, CTNNB1, KRAS, ERBB2, & PIK3CA. A questionnaire directed to treating oncologists evaluating impact of MA on adjuvant management decisions and counselling was utilized.

Results

189 patients amongst 7 treating gynecologic oncologists were evaluated over the initial 13 months. Primary stage of disease was; I: 139 (73.5%), II: 11(5.8%), III: 27 (14.3%), IV: 12 (6.4%). Prognostic classifiers were: POLE: 10 (5.3%); MMRd 52 (27.5%); NSMP: 86 (45.5%); and p53: 41 (21.7%), including multiple-classifiers: 10 (5.3%) MMRd-p53 and 4 (2.1%) POLE-p53. The classifiers with the most impact for providers were MMRd: 27 (14.3%) and p53: 22 (11.6%). Prognostic classification impacted patient counselling in 72 (38.1%) of patients (POLE 66.7%; MMRd 59.5%; p53 52.5%; NSMP 12.6%; p<0.001), with NSMP having the least impact. MA impacted treatment recommendations in 19 (10%) of patients. MA altered treatment recommendations compared to recommendations by histological properties in 8 (4.2%) patients. MA significantly impacted treatment recommendations with increasing stage (I: 5.8%, II: 9.1%, III: 22.2%, IV: 33.3%, p=0.002). MA significantly altered treatment recommendations deviating from histological recommendations with increasing stage (I: 1.4%, II: n/a, III: 14.8%, IV: 16.7%, p=0.002).

Conclusions

Comprehensive uniform molecular analysis of endometrial carcinoma via combined IHC and NGS upon primary resection is feasible and contributes to patient counseling and treatment recommendations.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The University of Colorado.

Funding

Has not received any funding.

Disclosure

B.R. Corr: Financial Interests, Institutional, Advisory Board: GSK, Gilead, Immunogen, Zentalis, Merck; Financial Interests, Institutional, Funding: Clovis, Immunogen. C. Walsh: Financial Interests, Institutional, Advisory Board: Immunogen, Regeneron. L. Brubaker: Financial Interests, Institutional, Advisory Board: AstraZeneca. S.R. Guntupalli: Financial Interests, Institutional, Advisory Board: Seagen. D. Aisner: Financial Interests, Institutional, Funding: Takeda, Loxo Oncology, Eli Lily, Sanofi Genzyme, AstraZeneca, Genentech, AbbVie, Janssen. All other authors have declared no conflicts of interest.