Author's reply to: Effect of adjuvant treatment on survival in 2023 FIGO stage IIC endometrial cancer

To the Editor,

We greatly appreciate the letter from Dr. Utku Akgor in response to our article and their excellent research on this important issue [1]. Dr. Utku Akgor analyzed prognostic factors in 612 patients with 2023 International Federation of Gynecology and Obstetrics (FIGO) stage IIC endometrial cancer from 7 medical centers in Turkey and evaluated the survival effect of adjuvant treatment in these patients.

While both the Turkish study and ours included a well-defined population of 2023 FIGO stage IIC endometrial cancer patients, the results of 2 studies differed on the prognostic factors impacting survival outcomes and patient subgroups having a survival benefit from adjuvant treatment. Our study found that presence of lymphovascular space invasion (LVSI) and non-endometrioid histological types were associated with shorter recurrence-free survival (RFS) and overall survival (OS), while only histological types could impact OS. In Turkish study, deep myometrial invasion (MI) along with LVSI was associated with shorter RFS and OS. Patients with LVSI could benefit from adjuvant treatment in both studies. This advantage on OS was more significant among patients with grade 3 endometrioid tumors in our subgroup analysis. In addition to cases with LVSI, Turkish study demonstrated that the survival benefit of adjuvant treatment on OS could be observed in patients with deep MI. As for the optimal adjuvant treatment modality, radiotherapy alone seemed to be sufficient for our specific subgroups.

The 2023 staging system for endometrial carcinoma emphasizes the importance of LVSI and histological types compared with previous staging system, aiming to provide a more accurate prognostic information [2]. In the new staging system, the stage IIC is defined as aggressive histological types with any myometrial involvement. Thus, the significance of LVSI and depth of MI among endometrial cancers with aggressive histological types cannot be distinguished by stage. Additionally, the aggressive histological types include grade 3 endometrioid carcinoma and high-grade non-endometrioid carcinoma, 2 distinct groups with different tumor pathology, clinical presentations, and prognoses [3]. Therefore, we thought that classifying these 2023 FIGO stage IIC endometrial cancer patients with different extent of LVSI and MI into the same stage may not accurately represent overall prognosis, as evidenced by the inconsistent results from different studies, including this Turkish study.

In conclusion, early-stage endometrial cancer with aggressive histological types is a heterogenous disease with varying prognoses. Current evidence supports molecular profiling can provide diagnostic, prognostic, and treatment-related information to optimize management of patients with endometrial cancer [4]. The lack of molecular classification is a limitation in both studies, and it is essential to incorporate molecular information into the future research. Like the investigation of new treatment modalities for other types of gynecologic cancer [5, 6], potential targets may be selected from detailed molecular/genomic profiling to develop therapeutic strategies for endometrial cancers in the era of precision medicine. However, in the absence of molecular information, pathological factors such as histological types, LVSI, and depth of MI remain important considerations for adjuvant treatment in patients with high-grade early-stage endometrial cancer.