Real-world characteristics and treatment patterns in Chinese patients with newly diagnosed endometrial cancer

To the Editor: Endometrial cancer (EC) ranks as the second most common gynecologic malignancy in China, with rising incidence rates.[1,2] In China, the 5-year survival rate for EC patients has improved from 55.1% in 2003–2005 to 72.8% in 2012–2015. However, due to sociodemographic, clinicopathological, and treatment-related factors, this remains lower than the 81% in the United States.[3,4] EC is a complex disease with multiple risk factors, distinct histological subtypes, and a variety of available therapeutic options. However, we know very little about the real-world characteristics and treatment patterns of EC in China.[5] Therefore, this large-scale, multicenter study aimed to investigate the demographic, histopathological, and molecular features of newly diagnosed EC patients in China, as well as to provide insights into current treatment patterns. A chart review was performed to extract variables from the medical records between January 1, 2015 and December 31, 2019 across eight sites in China representing various geographic regions. The inclusion criteria were: (1) newly diagnosed EC within the study period, (2) age ≥18 years at diagnosis, (3) histologically confirmed EC, and (4) available pathological data. Patients were excluded if the cancer did not originate from the endometrium, or if they had participated in clinical trials for anti-tumor purposes. The study protocol was approved by the Human Research Ethics Committees of all participating centers (ethics approval number in leading site: 2020(041)). Since this study is a retrospective study and patient personal information cannot be obtained, informed consent is waived. The demographic and clinicopathological data at diagnosis as well as the treatment patterns received within 6 months post-diagnosis were collected. A total of 1397 patients were enrolled, with an average age of 53.5 years old and half were below 55 years old [Supplementary Figure 1, https://links.lww.com/CM9/C388]. Among them, 65.4% (914/1397) were postmenopausal. The International Federation of Gynaecology and Obstetrics (FIGO) 2009 staging distribution was: Stage I (63.4%) [885/1397], Stage II (10.1%) [141/1397], Stage III (14.8%) [207/1397], and Stage IV (1.6%) [23/1397]. The predominant pathological types were pure endometrioid cancer (89.8%) [1254/1397] and serous carcinoma (5.1%) [71/1397]. Myometrial infiltration was <1/2 in 48.6% (679/1397) and ≥1/2 in 23.7% (331/1397). Of the tumors, 66.1% (924/1397) were low-grade (G1-2) and 23.2% (324/1397) high-grade (G3). Lymphovascular space invasion (LVSI) status was negative in 31.9% (446/1397) of cases, positive in 17.0% (237/1397), and unassessed in the remaining 51.1% (714/1397). Estrogen receptor (ER) positivity was observed in 91.0% (977/1074) and progesterone receptor (PR) positivity in 85.2% (904/1061) [Supplementary Table 1, https://links.lww.com/CM9/C388]. Microsatellite instability (MSI)/mismatch repair (MMR) testing was performed in 41.5% (580/1397) of patients, with an microsatellite instability high (MSI-H)/mismatch repair deficient (dMMR) rate of 26.6% (107/402). Among patients tested for MSI, 24.3% (27/111) were diagnosed with MSI-H, and 26.5% (106/400) of those with MMR exhibited dMMR [Supplementary Figure 2, https://links.lww.com/CM9/C388]. The loss rates of the MutS Homolog 6 (MSH6), MutS Homolog 2 (MSH2), Postmeiotic Segregation Increased 2 (PMS2) and MutL Homolog 1 (MLH1) proteins were 9.6% (55/574), 8.3% (48/575), 22.4% (128/572), and 18.0% (104/577), respectively. Treatment patterns revealed that 99.6% (1391/1397) underwent surgery, 58.8% (822/1397) received chemotherapy, 29.6% (413/1397) received radiotherapy, 1.7% (24/1397) received endocrine therapy, and 0.3% (4/1397) received targeted therapy or immunotherapy. The most common surgery type was total hysterectomy with bilateral salpingo-oophorectomy (TH/BSO), performed in 71.2% (990/1391) of cases. Platinum combined with taxane was the main chemotherapy regimen (95.9% [788/822]). For radiotherapy, external beam radiography was the most frequent (46.7% [193/413]), followed by combination radiotherapy (21.5% [89/413]) and brachytherapy (17.7% [73/413]) [Table 1]. Table 1 - Overall treatment patterns for newly diagnosed endometrial cancer patients. Overall treatment pattern No of patients (N = 1397, %) Surgery 1391 (99.6) Total hysterectomy + bilateral salpingo-oophorectomy 990 (71.2) Radical/extensive hysterectomy 279 (20.1) Modified extensive hysterectomy 90 (6.5) Total hysterectomy 11 (0.8) Other surgery type 32 (2.3) Chemotherapy 822 (58.8) Platinum 27 (3.3) Taxanes 4 (0.5) Platinum and taxanes 788 (95.9) Radiotherapy 413 (29.6) Brachytherapy 73 (17.7) External beam radiography 193 (46.7) Combination radiotherapy 89 (21.5) Others regimen 58 (14.0) Chemotherapy and radiotherapy 306 (21.9) Chemotherapy followed by radiotherapy 60 (4.3) Radiotherapy followed by chemotherapy 7 (0.5) Sandwich chemotherapy and radiotherapy 95 (6.8) Concurrent chemotherapy and radiotherapy 144 (10.3) Endocrine therapy 24 (1.7) Targeted therapy 4 (0.3) Immunotherapy 4 (0.3) Among 1391 surgical patients, adjuvant therapy was given to 66.2% (921/1391) of surgical patients, and 1.7% (24/1391) received neoadjuvant therapy. In more detail, 20.9% (291/1391) received adjuvant chemoradiotherapy, 37.6% (523/1391) underwent adjuvant chemotherapy, 7.7% (107/1391) received adjuvant radiotherapy, and 33.8% (470/1391) had no adjuvant therapy [Supplementary Figure 3, https://links.lww.com/CM9/C388]. In terms of adjuvant chemoradiotherapy, 44.3% was concurrent, 32.6% sandwich chemoradiotherapy, and 23.0% sequential. Treatment trends from 2016 onward showed an increase in surgery-only approaches for early-stage EC [Supplementary Figure 4, https://links.lww.com/CM9/C388]. Our findings confirm that EC mainly affects postmenopausal women. However, Chinese EC patients are frequently diagnosed at a younger median age (early 50s), notably 10 years earlier than reported in the SEER dataset. Eleven percent of our population is younger than 45 years, which is higher than the 7.1% reported in the SEER dataset.[4] Our study observed a relatively low assessment rate of LVSI, with results mostly categorized with a two-tiered system (absent or present) until 2019. However, guidelines have adopted a three-tiered LVSI evaluation system (no, focal, and substantial) since 2020, identifying substantial LVSI as a significant prognostic factor to inform adjuvant treatment decisions.[6] Therefore, it is imperative to emphasize the importance of identifying and defining LVSI to establish a standardized framework for future risk stratification. Patients with MSI-H/dMMR have been associated with a more favorable prognosis and may benefit from immunotherapy. Globally, about 25–30% of EC patients are MSI-H/dMMR, consistent with our study’s rate of 26.6%.[7,8] However, only approximately 40% of newly diagnosed EC patients underwent MSI or MMR testing in clinical practice, highlighting the need to enhance molecular testing. EC treatment in China generally aligns with international guidelines, with surgery as the primary treatment. Incomplete risk stratification may account for the high rates of adjuvant chemotherapy and radiation in this study compared to the United States.[9] Further analysis is required to understand the impact of risk stratification on treatment. In addition, despite the growing use of brachytherapy as the main adjuvant treatment option for high-/intermediate-risk EC patients, our study noted a higher use of external beam radiation.[10] Limited radiotherapy resources, expertise, and high brachytherapy costs may contribute to this discrepancy. Nevertheless, there is a positive shift toward standardized EC management in China, evidenced by the increasing use of surgery alone for early-stage EC from 2015 to 2019. As a retrospective observational study, data quality may vary across centers, and limited follow-up with high patient turnover prevented survival analysis, making it difficult to link patient characteristics with prognosis. However, this is the largest multicenter study to date on newly diagnosed EC in China, involving both general and tumor hospitals across eight regions. The chart review method enhances data reliability and highlights differences between China and other countries, providing a solid foundation for improving EC care in China. In summary, our study reveals that Chinese patients are frequently diagnosed in their early 50s, with most presenting at FIGO Stage I. Approximately 41.5% of patients underwent MSI/MMR testing, with MSI-H/dMMR present in about one-quarter of cases. Surgery was the primary treatment, often combined with adjuvant chemotherapy or radiotherapy, while immunotherapy use was minimal before 2020. China’s EC management is advancing and continued efforts to improve risk stratification and treatment management strategies are crucial. Acknowledgments Editorial assistance for this article was provided by Medjaden Inc. Conflicts of interest This study was funded by MSD China. Min Zhang, Binqi Zhang, Huirong Mao, and Fengshi Dong are employed by MSD China. The other authors report no competing interest.