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Endometrial cancer (EC) is the most common gynecologic malignancy, with worldwide increasing incidence and disease-associated mortality. Although most patients with EC are diagnosed with early-stage disease, systemic treatment options for patients with advanced or recurrent EC have historically been limited. EC-focused clinical trials and the ensuing therapeutic landscape have expanded since The Cancer Genome Atlas (TCGA) identified 4 distinct EC subgroups associated with differential survival. This endeavor revolutionized our understanding of the genomic characterization of EC as well as molecular drivers of this heterogeneous malignancy, leading to precision oncology approaches to therapeutics and advancement in treatment options. This review describes the current status of and recent advancements in therapeutic options for patients with advanced and recurrent EC. The NCCN Guidelines for Uterine Neoplasms provide detailed recommendations regarding the diagnosis, workup, and management of EC.

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identify trends associated with incidence of high risk endometrial cancers in native versus US Asians. Methods Data were obtained from the United States Cancer Statistics and Republic of China Cancer Registry from 2001-2017. We defined high risk cancers as grade 3 endometrial (G3E), serous, clear cell, and carcinosarcoma. SEER*Stat 8.3.9.2 and Joinpoint regression program 4.9.0.0 were used to calculate trends. Results Of 55,031 endometrial cancer patients, 28,204 (51%) were US and 26,827 (49%) were native Asians. In subset, serous cancer incidence (per 100,000) in 2017 was highest in US Asians (serous 1.25, G3E 1.15, carcinosarcoma 0.82) whereas G3E was over four fold higher than other cells types in native Asians (G3E 2.63, serous 0.64, carcinosarcoma 0.51). Over the 17 year study period, the incidence of high risk cancers increased annually at 2.3% in US Asians (serous increase: 6.3%) compared to 21.9% in native Asians (G3E increase: 14.8%) (p<0.001). In analyzing mortality trends, US Asians had a higher annual increase in mortality compared to native Asians (+2.11% vs -2.99%). US Asians had an over two fold higher risk of death for ages 70+ at 22.9 (per 100,000) compared to 10.6 in native Asians. Conclusions The incidence for high risk uterine cancer is increasing significantly more in the Republic of China vs. US. However, mortality rates are higher in the US. Further research is needed to better understand the social determinants and regional differences that may contribute to these trends.

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.