Risk Stratification of Stage I Grade 3 Endometrioid Endometrial Carcinoma in the Era of Molecular Classification.

Purpose: The role of adjuvant therapy in stage I grade 3 endometrioid endometrial carcinoma (EEC) is debatable. We sought to define the agreement between Post Operative Radiation Therapy in Endometrial Carcinoma 1 (PORTEC-1) high-intermediate risk (HIR) and Gynecologic Oncology Group (GOG)-99 HIR criteria, assess their concordance with The Cancer Genome Atlas molecular subtypes, and evaluate oncologic outcomes in this population.
Methods: We identified patients with stage I grade 3 EECs who underwent surgical staging at our institution from January 2014 to January 2020. Patients were stratified into PORTEC-1 HIR, GOG-99 HIR, and The Cancer Genome Atlas molecular subtypes. Adjuvant treatment, and progression-free survival (PFS), and overall survival (OS) were analyzed.
Results: Seventy-five patients were included. The agreement between PORTEC-1 and GOG-99 HIR classification was 68% (95% CI, 56.2 to 78.3), with a kappa of 0.36 ( P = .001). There was no agreement between PORTEC-1 or GOG-99 HIR classification and a dichotomized molecular classification (copy number-high [CN-H] v other subtypes), with a kappa of 0.03 ( P = .39) and -0.03 ( P = .601), respectively. There was no difference in PFS between PORTEC-1 HIR and non-HIR (HR, 10.9; 95% CI, 0.28 to 4.21) or between GOG-99 HIR and non-HIR (HR, 1.22; 95% CI, 0.32 to 4.6) stage I grade 3 EECs. Patients with CN-H compared with non-CN-H EEC had worse PFS (HR, 5.67; 95% CI, 1.73 to 18.63) and OS (HR, 5.05; 95% CI, 1.13 to 22.5).
Conclusion: In surgically staged patients with stage I grade 3 EEC, PORTEC-1 and GOG-99 HIR criteria were not prognostic and did not identify CN-H patients. Patients with CN-H EEC had worse PFS and OS compared with those with other molecular subtypes. The integration of the molecular classification with recognized clinicopathologic factors may identify patients with higher-risk stage I grade 3 EEC who benefit from additional therapy.
Competing Interests: Alexia IasonosStock and Other Owner Interests: Bristol Myers Squibb/SanofiConsulting and Advisory Role: Intelligencia, Mirati Therapeutics Carol AghajanianConsulting and Advisory Role: AbbVie, Eisai, AstraZeneca/Merck, Roche/Genentech, Repare TherapeuticsResearch Funding: Genentech/Roche, AbbVie, Clovis Oncology, AstraZeneca Vicky MakkerConsulting and Advisory Role: Eisai, Merck, Karyopharm Therapeutics, Takeda, ArQuie, IBM, GlaxoSmithKline, Clovis Oncology, Faeth Therapeutics, Novartis, Duality, ITeos Therapeutics, Kartos Therapeutics, LillyResearch Funding: Lilly, AstraZeneca, Eisai, Merck, Bristol Myers Squibb, Karyopharm Therapeutics, Takeda, Clovis Oncology, Bayer, Zymeworks, Duality, Faeth TherapeuticsTravel, Accommodations, Expenses: Eisai, Merck, Karyopharm TherapeuticsOther Relationship: IBM Mario M. Leitao JrHonoraria: Intuitive SurgicalConsulting and Advisory Role: Intuitive Surgical, Ethicon/Johnson & Johnson, Medtronic, TakedaResearch Funding: KCITravel, Accommodations, Expenses: Intuitive Surgical Nadeem R. Abu-RustumHonoraria: Prime Oncology, NCCMResearch Funding: GRAILTravel, Accommodations, Expenses: Prime Oncology Britta WeigeltStock and Other Owner Interests: Repare Therapeutics (I)Consulting and Advisory Role: Ventana Medical Systems, VolitionRx, PAIGE, Goldman Sachs, Repare Therapeutics, Lilly (I)No other potential conflicts of interest were reported.