Disease Burden and Treatment Pattern of Advanced or Recurrent Endometrial Cancer in Korea: A Nationwide Database (DIRECTION) Study

Hyun-Woong Cho; Se Ik Kim; Min-Ji Bae; Kyoung-Eun Kwon; Choung Won Jung; Young Eun Lee; Ji Yoon Ahn; Kidong Kim

doi:10.4143/crt.2025.065

Articles

Page Path: HOME > J Korean Cancer Assoc > Ahead-of print articles > Article

Original Article Disease Burden and Treatment Pattern of Advanced or Recurrent Endometrial Cancer in Korea: A Nationwide Database (DIRECTION) Study: Hyun-Woong Cho¹, Se Ik Kim², Min-Ji Bae³, Kyoung-Eun Kwon⁴, Choung Won Jung⁴, Young Eun Lee⁴, Ji Yoon Ahn⁴, Kidong Kim⁵; DOI: https://doi.org/10.4143/crt.2025.065
Published online: October 20, 2025

¹Department of Obstetrics and Gynecology, Korea University Guro Hospital, Seoul, Korea

²Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Korea

³GSK Korea Ltd., Seoul, Korea

⁴IQVIA Solutions Korea Ltd., Seoul, Korea

⁵Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, Korea

Correspondence: Kidong Kim, Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, 82 Gumi-ro 173beon-gil, Bundang-gu, Seongnam 13620, Korea
Tel: 82-31-787-7262 E-mail: kidong.kim.md@gmail.com

^*Hyun-Woong Cho and Se Ik Kim contributed equally to this work.

• Received: January 15, 2025 • Accepted: October 16, 2025

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

1,877 Views
115 Download

Full Article

Download PDF

Abstract

Purpose
Advanced/recurrent endometrial cancer (EC) patients have a poor prognosis, with higher recurrence and mortality than early-stage. However, as the real-world disease burden in these patients remains unclear, we aimed to investigate systemic anticancer therapy (SACT) patterns, healthcare resource utilization (HCRU), and costs in advanced/recurrent EC patients.
Materials and Methods
This nationwide population-based study used Korean claims data from 2008 to 2022. Adult patients with advanced/recurrent EC who received first-line SACT were included. For advanced EC, first-line SACT was defined as the initial therapy following EC diagnosis, while for recurrent EC it was defined as the initial therapy after recurrence following completion of primary therapy. We analyzed SACT patterns, prognosis, all cause- and EC-related HCRU, and costs.
Results
A total of 2,704 EC patients were included. The most commonly used SACT was platinum-based regimen. From the first to third line, median values of SACT-free interval (18.40, 5.03, and 3.22 months) and time to next treatment (TTNT, 25.43, 9.27 and 6.44 months) showed decreasing trends. All-cause/EC-related HCRU and costs were increased with SACT progression; all-cause inpatient visits and total costs increased from 0.58 to 1.04 times per-patient-per-month (PPPM) and from $1,197.96 to $2,354.37 USD PPPM.
Conclusion
This study demonstrated significant variability in SACT regimen sequence, highlighting the lack of consensus on standard treatment after disease relapse. Shorter TTNT and SACT-free intervals and higher HCRU and costs in later lines indicate worsening prognosis and increasing disease burden. These findings suggest the urgent need for more effective treatments, including new therapeutic agents, to address the unmet clinical needs of advanced/recurrent EC patients.
Key words: Endometrial neoplasms, Anticancer therapy, Treatment pattern, Socioeconomic burden, Population-based cohort study

Introduction

Endometrial cancer (EC) is one of the most common gynecologic malignancies threatening women’s health, accounting for 8.4% of new malignancies in women worldwide [1]. Aligned with the global trends, the incidence of EC in Korea has also been increasing in recent years [2,3]. The number of newly diagnosed EC cases is estimated to be over 4,000 a year during 2024, making it the seventh most common cancer in Korean females [4].

In comparison to early-stage EC, patients with advanced or recurrent EC have worse prognosis and higher burden of disease [5]. Previous studies found that patients with International Federation of Gynecology and Obstetrics (FIGO) stage III or IV EC have a poor 5-year survival rate compared to those with FIGO stage I or II EC (≤ 15% vs. > 74%) [6]. The median 5-year survival rate of patients with recurrent EC is known to range from 17% to 55% [7].

While the mainstay of therapy in advanced or recurrent EC is systemic antineoplastic or hormonal agents, a shift in the treatment landscape is expected since new treatment options have been introduced in recent years [8,9]. Among the novel therapies for EC, immune checkpoint inhibitors have emerged as a novel and efficacious treatment modality [10]. For example, dostarlimab is the first programmed cell death-1 (PD-1) inhibitor approved as monotherapy for mismatch repair deficient (dMMR) EC by the European Medicines Agency (EMA), U.S. Food and Drug Administration (FDA), and Ministry of Food and Drug Safety of Korea (MFDS). Dostarlimab is indicated for patients with advanced or recurrent EC who have progressed on or after platinum-based chemotherapy with dMMR/microsatellite instability–high (MSI-H) tumors, based on the results from the GARNET trial [11]. In addition to monotherapy, the combination of dostarlimab and carboplatin-paclitaxel in the first-line primary advanced or recurrent setting demonstrated a statistically significant reduction in the risk of mortality compared to carboplatin-paclitaxel alone in the RUBY trial [12].

Although newly approved immunotherapy options have shown promise in advanced or recurrent EC, chemotherapy remains the mainstay of systemic anticancer treatment due to geographic availability and limited access to novel agents [10]. Given this situation, identifying unmet needs within the overall landscape of advanced or recurrent treatment is necessary. In literature, previous nationwide observational studies have examined treatment patterns in EC and associated healthcare resource use (HCRU) and healthcare costs [13-15], but not in Korea.

Therefore, this real-world observational study aimed to assess the treatment patterns and economic burden of disease for advanced or recurrent EC in Korea according to disease progression by using the National Health Insurance (NHI) database. We investigated the treatment patterns by analyzing treatment duration, interval times, time to next treatment, and treatment sequence according to each line of therapy. Furthermore, the latest HCRU and costs associated with advanced or recurrent EC across different lines of therapy were also evaluated.

Materials and Methods

1. Data source

This retrospective cohort study used claims data between January 2008 and December 2022, provided from the Health Insurance Review and Assessment Service (HIRA) database in Korea, which covers approximately 98% of the Korean population. The HIRA database contains sociodemographic and healthcare service information, such as age, sex, insurance eligibility, ambulatory care utilization, hospitalizations, and visit dates [16,17]. Diagnostic data are coded using the International Classification of Diseases 10th revision (ICD-10) and the prescription information includes the official code of the prescribed drugs, date of prescription, days of supply, and administration routes. All data were encrypted and provided with anonymous identification numbers for research purposes to protect personal information.

2. Study design

Patients with incident EC and their diagnosis date (diagnosis index date) were identified using the patient diagnosis record during the index period and by excluding the past diagnosis history of EC in exclusion assessment window. Among patients with newly diagnosed EC, advanced or recurrent EC patients were identified based on treatment modalities in the first line of therapy (LoT 1) and/or their subsequent therapies as a proxy for disease severity. The index date of first line of systemic anticancer therapy (SACT) was defined as the start date of the initial SACT for advanced or recurrent EC. Patients were followed upon the start date of the first line of SACT until the end of the corresponding line of SACT, death or the end of the study period (December 31, 2022) (S1, S2 Figs., Supplementary Methods).

3. Study participants

Patients with advanced or recurrent EC were identified from the HIRA dataset including patients who were aged 19 years or above, and had at least one outpatient or inpatient claims (ICD-10; C54.0, C54.1, C54.3, C54.8, C54.9) with the rare and intractable disease (RID) code for cancer (V193) during the index period. Patients who did not receive systemic therapy after their diagnosis index date were excluded from the study because it was hypothesized that they were more likely to have early-stage disease. Additionally, patients were excluded if they had any history of EC diagnosis or cancer other than EC during 24 months prior to the diagnosis index date. Patients who had the initial impression of EC but were diagnosed with another gynecologic cancer as the actual diagnosis within two months after EC diagnosis were also excluded. Advanced and recurrent EC patients were categorized based on the initial treatment modality using a logical algorithm described in the Supplementary Methods.

For the final study population, patients who received hormonal therapy without any other SACT as the first modality of LoT 1 were regarded as receiving therapy for a fertility-sparing purpose and were further excluded. In addition, patients who had diagnosis records of primary cancers other than EC between the diagnosis index date and the index date of first line of SACT were also excluded.

4. Exposures and covariates

EC-related surgery and radiotherapy were defined by using the procedure codes that are listed in S3 Table. SACT was defined using prescription records, including relevant codes for systemic chemotherapy and hormonal therapy that are reimbursed for EC treatment in Korea during the study period (S4 Table). The line of SACT for advanced or recurrent EC was determined for each patient based on the identification algorithm adopted to local clinical practice in Korea from previous studies [16,17] (S5 Fig., Supplementary Methods).

Regarding the covariates, baseline characteristics including age, health insurance type, institution type and region were assessed on the index date of the first line of SACT. Additionally, comorbidities were assessed using the modified Charlson Comorbidity Index (mCCI) [18,19] (S6 Table). Type of treatment modalities in LoT 1, number of LoTs between EC diagnosis and first line of SACT, and interval time between the end of LoT 1 and the start of LoT 2 were also assessed for recurrent EC patients.

5. Outcomes

Treatment patterns, HCRU, and costs among advanced or recurrent EC patients were evaluated as the outcomes of this study. Treatment patterns according to line of SACT were assessed during the observation period, which includes interval time, time to next line of SACT (TTNT), and treatment sequence. Each regimen classification was assessed both in drug-level (e.g., carboplatin+paclitaxel) and class-level (e.g., taxanes+platinum) (S7 Table). For analysis of all-cause and EC-related HCRU and costs of each SACT line, all HCRU and costs for related NHI-reimbursed resources and services incurred during the period from the start of the line of SACT to the start of the next line of SACT were calculated. If no subsequent line of SACT has been observed, HCRU and costs from the start date of the last SACT to the end of the observation period were used. HCRU was summarized as the number of inpatient visits, outpatient visits, emergency department (ED) visits, and days of hospital stay, while costs were summarized as inpatient, outpatient, pharmacy, and total medical costs. With respect to the cost analysis, the direct medical costs of the reimbursement service were assessed. This assessment encompassed both patient out-of-pocket expenses and the insurer’s shared reimbursement costs. The insurer’s portion was calculated based on the final approved reimbursement amounts by the NHI.

6. Statistical analysis

The results were analysed for the entire study population and for subgroups according to whether the patients had advanced or recurrent EC. The baseline characteristics of our study population were presented as counts (proportions) for categorical variables and means (standard deviations, SD) for continuous variables. Differences between advanced and recurrent EC groups were tested using t test or Wilcoxon test for numeric variables and chi-square test or Fisher’s exact test for categorical variables where appropriate. All statistical tests were two-sided with a significance level of 0.05.

Treatment regimen and treatment sequence were summarized from first to fourth line, and the number of patients and proportions with each combination of regimens in each line of SACT were presented using descriptive statistics. Beyond the fourth line of SACT, regimens have been omitted due to their low frequency. The regimen of SACT was classified as undetermined when a patient was censored before the 30th day since that SACT initiation, and treatment sequences with a frequency less than three were presented as others.

SACT-free interval time and TTNT for each line for advanced or recurrent EC were analyzed using descriptive statistics and Kaplan-Meier (KM) estimator to account for censoring due to death, occurrence of the primary cancers other than EC, or end of study period. All-cause/EC-related HCRU and costs were presented as the mean (SD) and median (interquartile range, IQR) by each line of SACT per patient per month (PPPM). To assess the costs, Korean won (KRW) were converted into U.S. dollar (USD) using the average exchange rate in 2022 (1 USD=1,291.95 KRW) and adjusted to the calendar year of 2022 using the Consumer Price Index (CPI) for health of Korea (S8 Table). SACT-free interval time, TTNT, HCRU and costs were calculated for all lines of SACT from the index date of the first line of SACT to the patients’ observation end point. However, lines from the fourth line onward were not presented due to the small number of applicable patients.

Results

1. Study population

Among 50,901 women who were diagnosed with EC between January 2010 and September 2022, 22,573 were identified as new EC patients without a history of EC or other cancers. Of these, 2,704 EC patients were included in the final analysis, which comprised 910 newly diagnosed advanced EC patients and 1,794 recurrent EC patients (Fig. 1).

Patient characteristics are depicted in Table 1. The majority (71.0%) were age 50-69 years at the date of EC diagnosis, and the median observation period was 19.48 months (IQR, 7.29 to 43.53 months). The primary reason for follow-up loss was the end of the study period, which resulted in the loss of 56.8% of the study population. Of the remaining participants, 29.6% died, and 13.6% developed a second primary cancer (SPC). The mean (±SD) mCCI score was significantly higher in recurrent EC patients compared to that in advanced EC patients (5.74±3.26 vs. 3.91±2.89, p < 0.001). The most common comorbidity was mild liver disease in the recurrent EC group and chronic pulmonary disease in the advanced EC group.

In terms of treatment modality of LoT 1, majority (95.6%) of recurrent EC patients received surgery as primary intervention and only 4.4% have received radiotherapy. Meanwhile, all the patients in the advanced group have received SACT as the primary treatment of LoT 1. Among those, only 115 (12.6%) received surgery after SACT during LoT 1.

Recurrent EC patients received at least one and up to four LoTs before starting the first line of SACT, and the median time between the end of LoT 1 and start of LoT 2 was 9.58 months (Table 1).

2. Treatment patterns

Platinum-based combination regimens were the most commonly prescribed regimen across all lines of therapy (Fig. 2). In the first line, the most frequently prescribed regimen was a taxanes plus platinum (42.0%), most of which consisted of the paclitaxel and carboplatin combination. In the second line, the most frequently prescribed regimen was doxorubicin plus platinum (25.7% of all patients who started second line of SACT), most of which consisted of the doxorubicin and cisplatin combination. In the third line and beyond, other platinum-based combination regimens were most frequently prescribed (Table 2, S9 Table).

In the recurrent EC group, the second most common regimen in the first line was doxorubicin plus platinum (21.2%), most of which were the doxorubicin plus cisplatin combination, and was platinum monotherapy (23.5%), which consisted mainly of cisplatin or carboplatin, in advanced EC group. In the second and third lines, the second most common regimens were other platinum-based combinations and hormone therapy (23.7% and 14.6%, respectively) in recurrent EC patients, and doxorubicin plus platinum (26.5% and 25.0%, respectively) in advanced EC patients (Table 2, S9 Table).

Only 11.20% of all EC patients received regimens that do not contain platinum at the first line of SACT: hormone therapy (7.1%), non-platinum monotherapy (2.9%), and combinations not containing platinum (1.3%). The proportion of patients who were treated with those regimens tended to increase in the later line of SACTs (14.5%, 23.0%, and 21.0% in the second, third, and fourth line) (Table 2, S9 Table).

As for the treatment sequence in SACT, over half of the patients (69.1%) received only first-line SACT. Only 837 (31.0%), 305 (11.3%), and 100 (3.7%) patients started the second, third, and fourth line of SACT during the follow-up period. Among those who received additional lines of therapy, the most common treatment sequence was the combination of taxanes and platinum for first line and the combination of doxorubicin and platinum for second line (n=95, 3.5%), followed by the sequence where both first and second line were a combination of taxanes and platinum (n=37, 1.4%) (Table 3, S10 Table).

All median values of SACT-free interval time and TTNT decreased as the line of treatment increased from the first to third line. The KM-estimated median SACT-free interval time and TTNT for the first to third line of SACT were 18.40, 5.03, and 3.22 months and 25.43, 9.27 and 6.44 months, respectively. When comparing between groups based on EC type, the advanced EC group showed a longer tendency for SACT-free interval time and TTNT across all treatment lines relative to those within the recurrent EC group; however, this was statistically significant only at the first line (Fig. 3).

3. HCRU and costs

All the median values of HCRU and costs increased in the later line of SACT. For all-cause HCRU analysis, the median number of inpatient visits, defined as ≥ 1 overnight stays in inpatient settings with or without EC diagnosis code within the claim records, were 0.58, 0.97 and 1.04 times PPPM in the first, second and third line of SACT, respectively. Similarly, the median number of all-cause ED visits and days of hospital stay (0.13, 0.23, and 0.32 times PPPM and 3.00, 4.00, and 5.00 days per hospitalization in the first, second and third line of SACT, respectively) increased at each line of treatment (Table 4). EC-related HCRU had a similar trend with all-cause HCRU (S11 Table).

The median all-cause total costs increased from 1,197.96 USD PPPM in the first line to 2,354.37 USD PPPM in the third line of SACT. Consistently, the median EC-related total costs gradually increased from 1,048.11 USD PPPM in the first line to 1,980.92 USD PPPM in the third line of SACT. In terms of inpatient cost, which accounted for the more than half of the total cost across the line of SACTs, there was an increasing trend from 796.96 USD PPPM in the first line to 2,108.34 USD PPPM in the third line of SACT for all cause and from 765.66 USD PPPM in the first line to 1,877.53 USD PPPM in the third line of SACT for EC-related cost (Fig. 4).

Discussion

This nationwide retrospective cohort study investigated the treatment patterns of SACT, HCRU, and costs for patients diagnosed with advanced or recurrent EC in Korea for the first time. Our study results demonstrated significant variability of treatment patterns in real-world practice, especially for advanced or recurrent EC patients who have progressed after a platinum-based regimen, highlighting unmet needs in this population.

Among 28,385 newly diagnosed EC patients, 2,704 patients (9.5%) were identified as advanced or recurrent EC. In the final study population, patients aged 50-59 years at EC diagnosis accounted for over 40%. The age distribution within the study population was in accordance with the known epidemiology of advanced or recurrent EC in Korea [20]. During the follow-up period, 13.6% of patients were censored due to the development of a SPC. This may be attributable to two factors. First, in a Taiwanese study that followed EC patients for 20 years in 5-year intervals, the incidence of second primary cancers was consistently higher among patients aged ≥ 50 years compared to those aged < 50 (at 15 years: 15.9% vs. 7.4%) [21]. Given that over 80% of patients in our study population were aged ≥ 50 years, this age distribution should be taken into account when interpreting the incidence of SPCs in our cohort. Second, the fact that our study cohort exclusively included patients with advanced or recurrent EC, who tend to have higher cumulative exposure to cytotoxic agents, radiotherapy or surgery as well as prolonged disease trajectories, the likelihood of developing second malignancies may be inherently higher in this population [21,22].

For the treatment regimen, we observed substantial variability in systemic anticancer therapies used in clinical practice, including first-line therapy. Nonetheless, a combination therapy with taxanes and platinum, mostly paclitaxel plus carboplatin, was the most commonly utilized regimen in both advanced and recurrent EC patients (42.0%). This was consistent with the current practice guidelines [8,9], which are supported by outcomes from a clinical trial that demonstrated the non-inferiority of carboplatin plus paclitaxel compared to doxorubicin plus carboplatin plus paclitaxel, with a favorable relative safety profile, establishing carboplatin plus paclitaxel as the standard first-line chemotherapy in advanced and recurrent EC [23]. In the present study, only 11.2% of overall EC patients received regimens that do not contain platinum in the first line. The proportion of patients who were treated with non-platinum regimens tended to increase in the later line of SACTs (14.5%, 23.0%, and 21.0% in the second, third, and fourth lines). This finding was consistent with a nationwide retrospective study in the United States using U.S. commercial and Medicare databases where the authors found that the use of platinum-based regimens decreased as the LoT increased [24].

As for the treatment sequence of SACT, more than half of all treatment sequences ended at the first line of SACT. The finding that over half of patients did not receive treatment beyond the first line is consistent with results shown elsewhere. A study that used administrative health data from the National Cancer Registration and Analysis Service in England reported that 29.5% of patients started second-line treatment, while 8.9% of patients started third-line treatment. Moreover, the data revealed that patients with advanced or recurrent EC were treated with over 70 distinct SACT regimen sequences (drug-level data were not shown). Such a low rate of administration of the subsequent line of SACT and the considerable variability in regimen sequence may be due to the absence of a standard treatment for advanced or recurrent EC who progressed after a platinum-based regimen and limited effectiveness of treatments using existing chemotherapy agents, which collectively result in poor survival outcomes [13,25-27], These findings highlight the need for new treatment options in the first line to prevent or delay recurrence and for more effective options for those who do progress.

All values of SACT-free interval time and TTNT showed a decreasing trend from the first to third line. While there is a difference in the absolute numbers due to different definitions of line of therapy across studies, this decreasing trend is consistent with the results of previous studies. A previous study found that the median treatment-free interval decreased from 4·5 months in the first line of therapy to 2.8 and 0.5 months in the second and third line of therapy, respectively [24]. In the same study, the KM-estimated median TTNT was 19.3 months from second to third-line treatment, and 10.5 months from third to fourth-line treatment [24]. Another retrospective cohort study that used the nationwide Flatiron Health electronic health record in the United States demonstrated that TTNT was numerically higher in from first to second line than from second to third line of treatment (10.6 vs. 8.7 months, respectively) [28]. The decrease in these indices is an indication of a worsening of the prognosis as the disease progresses.

Regarding the HCRU and cost analysis, our study demonstrated that both the all-cause and EC-related HCRU, as well as the all-cause and EC-related healthcare costs increased in later line of SACT. A previous study based on a US claims database found consistent trends in HCRU and costs among newly diagnosed EC patients across the lines of therapy, although differences in absolute numbers exist depending on the treatment practices of each country [14]. The study found an increase in the mean inpatient visits from 0.07, 0.08, and 0.11 times PPPM in the first, second and third line of therapy, while the median inpatient visits in our study were 0.58, 0.97, and 1.04 times PPPM for the first, second and third line of SACT, respectively. As for the costs, direct comparisons of outcomes are difficult because of the differences in healthcare costs between countries, but the trend of increasing healthcare cost was consistent; the median total costs in the US database study increased from 3,684 USD PPPM in the first line of therapy to 6,695 USD PPPM in the second line of therapy, while the median value of all-cause total costs in this study were 1,197 and 1,709 USD PPPM in first and second line of SACT. The overall increase in disease burden in later lines of SACT that were identified in our study and previous studies highlights that the disease burden increases as the disease progresses.

In summary, the findings of this study indicate that the current standard of care among newly diagnosed advanced or recurrent EC patients has reached its clinical ceiling in real world practice with regard to prognosis and disease burden, even though newer immunotherapy options for EC have demonstrated improved outcome by numerous studies [10-12,29]. Increases in the SACT line consisting of conventional agents was related to increase in HCRU, higher costs, and worsening disease prognosis.

As mentioned in the introduction, immune checkpoint inhibitors have emerged as a novel and efficacious treatment modality in EC [10]. Anti–PD-1/programmed death-ligand 1 agents have been shown to have activity against MSI-H/mismatch repair–deficient solid tumors that have progressed after conventional therapy. Recently, pembrolizumab and dostarlimab, anti–PD-1 agents, were approved in several countries in the European Union (EU), United States, and Korea for the treatment of advanced or recurrent EC that had worsened after the initial treatment with chemotherapy by demonstrating significant therapeutic efficacy in clinical trials [11,29]. Moreover, the efficacy of combination regimens also has been corroborated by several studies. Lenvatinib plus pembrolizumab after at least one platinum-based chemotherapy showed a significantly longer progression-free survival and overall survival in both mismatch repair proficient and overall EC patients [30]. With the results of a randomized controlled trial, dostarlimab demonstrated its clinical efficacy by showing a significant reduction in mortality when combined with conventional chemotherapy as frontline treatment in an all-comers population [12]. As more of these immunotherapy-based regimens are introduced as new treatment approaches, there is a need to refine a standard of care for advanced or recurrent EC patients that consider these options [6].

A retrospective database study can provide valuable insights into real-world clinical practice and complement data from clinical trials. This nationwide population-based study included a large number of patients with advanced or recurrent EC, making our findings representative of the real-world clinical practice in Korea. Moreover, the 15-year timespan allows for a sufficient observation period, which in turn permits a more reliable and accurate analysis. Nevertheless, our study has several limitations. Firstly, the use of immune checkpoint inhibitors was not taken into consideration, as the study period ends December 2022, before these agents were used in earnest under the approval of the MFDS. Secondly, although we adjusted for changes in monetary value across the years by using the average 2022 exchange rate and applying the CPI for health, residual temporal effects due to changes in reimbursement policy or clinical practice guidelines may persist and should be considered when interpreting results. Additionally, there are several inherent limitations of a study using administrative claims data to consider. Although the sequential pattern of treatment was utilized as a proxy for disease severity and progression, this assumption may not perfectly reflect the actual classification of the study population. For instance, in terms of the definition of recurrence, those who started the second-line treatment due to toxicity from the previous treatment may not be differentiated from those who actually experienced disease recurrence. Likewise, for advanced EC, we defined as cases where patients received SACT including chemotherapy and hormone therapy as the initial therapy, assuming these cases are those who were ineligible for surgical intervention at EC diagnosis. This assumption may be captured more accurately with the term metastatic EC or EC with distant metastasis, but we adopted the term advanced EC in this study to ensure more inclusive and practical approach, given the constraints of insurance claims data. Furthermore, the algorithms applied to define LoT and line of SACT pose a potential risk of misclassification in the treatment patterns. To mitigate this risk, we devised the algorithms based on previous studies [16,17] and adapted them according to investigators’ discretion to consider local clinical practices. In addition, as the HIRA database does not capture detailed clinical variables including cancer stage or information on clinical response, treatment outcomes and prognosis were assessed through surrogate variables such as TTNT or the number of LoT between EC diagnosis and the start of first line of SACT as recurrent EC treatment. Lastly, since the HIRA database does not contain non-reimbursed healthcare services, actual economic burden of disease in terms of HCRU and cost may have been underestimated. Nevertheless, we endeavored to address these limitations based on previously published studies [11].

In conclusion, this nationwide population-based study provides a valuable insight into real-world treatment patterns and outcomes for patients with advanced or recurrent EC in Korea. The results of our study highlight the urgent unmet clinical need for the prompt implementation of novel treatment options as early in the treatment paradigm as possible, given that patients who progress experience an increase in disease burden, are less likely to receive additional treatment, and lead to increasing HCRU with each additional line of therapy. Novel first-line therapies may help prevent or delay progression and prevent the challenges in achieving optimal outcomes as patients with advanced or recurrent EC progress.

Electronic Supplementary Material

Supplementary materials are available at Cancer Research and Treatment website (https://www.e-crt.org).

crt-2025-065_S1_Fig.pdf

crt-2025-065_S2_Fig.pdf

crt-2025-065_S3_Table.pdf

crt-2025-065_S4_Table.pdf

crt-2025-065_S5_Fig.pdf

crt-2025-065_S6_Table.pdf

crt-2025-065_S7_Table.pdf

crt-2025-065_S8_Table.pdf

crt-2025-065_S9_Table.pdf

crt-2025-065_S10_Table.pdf

crt-2025-065_S11_Table.pdf

crt-2025-065-Supplementary-Methods.pdf

NOTES

Ethical Statement

This study was approved by the Institutional Review Board of the Korea University Medical Center (2024GR0331), and the need for informed consent was waived as the study was based on routinely collected insurance claims data.

Author Contributions

Conceived and designed the analysis: Cho HW, Kim SI, Bae MJ, Jung CW, Ahn JY, Kim K.

Collected the data: Cho HW, Kim SI.

Contributed data or analysis tools: Cho HW, Kim SI.

Performed the analysis: Kwon KE, Lee YE.

Wrote the paper: Kwon KE, Jung CW.

Interpretation: Cho HW, Kim SI, Bae MJ, Kwon KE, Lee YE, Kim K.

Reviewed and edited the paper: Cho HW, Kim SI, Bae MJ, Kwon KE, Jung CW, Lee YE, Ahn JY, Kim K.

Supervised the study: Kim K.

Administered project: Bae MJ, Kwon KE.

Acquired funding: Bae MJ.

Conflicts of Interest

HW Cho has non-financial interests with Merck, MSD, Roche, Takeda, Onconic therapeutics, Chong Kun Dang and GSK as a local PI, lecturer, or advisor. SI Kim, KE Kwon, CW Jung, YE Lee, J Ahn, and K Kim have no relevant competing interests to disclose. MJ Bae is a GSK employee and holds financial equities in GSK.

Funding

This study was funded by GSK (study no. 220738).

Acknowledgments

We would like to express our gratitude to all the individuals and organizations who contributed to this study. We thank the Health Insurance Review and Assessment Service (HIRA) of Korea for providing access to the claims database used in this research. We are also grateful to GSK for funding this study (study no. 220738). Medical writing support for this manuscript was provided by IQVIA Korea and was funded by GSK.

We extend our deepest appreciation to the investigators, data analysts, and clinical experts who provided their valuable insights and expertise throughout the study design and analysis process. Additionally, we acknowledge the Seoul National University Bundang Hospital Ethical Committee for their review and approval of the study protocol (IRB approval No. X-2309-854-902).

Lastly, we thank the patients whose anonymized data made this research possible, contributing to a greater understanding of the disease burden and treatment patterns of advanced or recurrent endometrial cancer in Korea.

Fig. 1.

Flow chart of study population selection. EC, endometrial cancer; LoT, line of therapy; RT, radiotherapy; SACT, systemic anticancer therapy.

Fig. 2.

Treatment sequence of systemic anticancer therapy (SACT) for overall endometrial cancer patients (sunburst plot).

Fig. 3.

Kaplan-Meier curves for systemic anticancer therapy (SACT)–free interval time (A) and time to next treatment (B). EC, endometrial cancer.

Fig. 4.

All-cause (A) and endometrial cancer (EC)–related (B) costs attributable to each line of therapy for recurrent or advanced EC.

Table 1.

Patient characteristics among recurrent or advanced EC patients

	Total	Recurrent	Advanced	p-value
Demographic characteristic
Age at diagnosis index date (yr)
19-29	34 (1.3)	20 (1.1)	14 (1.5)	0.06
30-39	117 (4.3)	78 (4.3)	39 (4.3)
40-49	339 (12.5)	208 (11.6)	131 (14.4)
50-59	1,122 (41.5)	734 (40.9)	388 (42.6)
60-69	798 (29.5)	551 (30.7)	247 (27.1)
70-79	258 (9.5)	183 (10.2)	75 (8.2)
≥ 80	36 (1.3)	20 (1.1)	16 (1.8)
Age at index date of 1st line of SACT (yr)
19-29	29 (1.1)	15 (0.8)	14 (1.5)	< 0.001
30-39	95 (3.5)	60 (3.3)	35 (3.8)
40-49	304 (11.2)	178 (9.9)	126 (13.8)
50-59	1,030 (38.1)	648 (36.1)	382 (42.0)
60-69	882 (32.6)	625 (34.8)	257 (28.2)
70-79	318 (11.8)	240 (13.4)	78 (8.6)
≥ 80	46 (1.7)	28 (1.6)	18 (2.0)
Insurance type
Health insurance	2,601 (96.2)	1,726 (96.2)	875 (96.2)	0.94
Medical aid	103 (3.8)	68 (3.8)	35 (3.8)
Institution type
General hospital	2,694 (99.6)	1,788 (99.7)	906 (99.6)	0.67
Hospital	9 (0.3)	5 (0.3)	4 (0.4)
Clinic	1 (0)	1 (0.1)	0
Institution region
Metropolitan area (Seoul, Gyeonggi, Incheon)	1,856 (68.6)	1,262 (70.3)	594 (65.3)	< 0.001
Gangwon	39 (1.4)	22 (1.2)	17 (1.9)
Gyoengsang	586 (21.7)	348 (19.4)	238 (26.2)
Chungcheong (including Sejong)	122 (4.5)	86 (4.8)	36 (4.0)
Jeolla (including Jeju)	101 (3.7)	76 (4.2)	25 (2.7)
Calendar year of EC diagnosis
2010	123 (4.5)	100 (5.6)	23 (2.5)	< 0.001
2011	143 (5.3)	107 (6.0)	36 (4.0)
2012	154 (5.7)	124 (6.9)	30 (3.3)
2013	159 (5.9)	135 (7.5)	24 (2.6)
2014	162 (6.0)	133 (7.4)	29 (3.2)
2015	195 (7.2)	157 (8.8)	38 (4.2)
2016	225 (8.3)	163 (9.1)	62 (6.8)
2017	252 (9.3)	168 (9.4)	84 (9.2)
2018	303 (11.2)	204 (11.4)	99 (10.9)
2019	306 (11.3)	179 (10.0)	127 (14.0)
2020	299 (11.1)	161 (9.0)	138 (15.2)
2021	236 (8.7)	121 (6.7)	115 (12.6)
2022	147 (5.4)	42 (2.3)	105 (11.5)
Calendar year of 1st line of SACT initiation
2010	34 (1.3)	17 (0.9)	17 (1.9)	< 0.001
2011	91 (3.4)	61 (3.4)	30 (3.3)
2012	99 (3.7)	72 (4.0)	27 (3.0)
2013	118 (4.4)	96 (5.4)	22 (2.4)
2014	130 (4.8)	104 (5.8)	26 (2.9)
2015	133 (4.9)	102 (5.7)	31 (3.4)
2016	151 (5.6)	101 (5.6)	50 (5.5)
2017	264 (9.8)	185 (10.3)	79 (8.7)
2018	287 (10.6)	183 (10.2)	104 (11.4)
2019	335 (12.4)	216 (12.0)	119 (13.1)
2020	366 (13.5)	212 (11.8)	154 (16.9)
2021	333 (12.3)	215 (12.0)	118 (13.0)
2022	363 (13.4)	230 (12.8)	133 (14.6)
Clinical characteristic
mCCI
Mean±SD	5.12±3.26	5.74±3.26	3.91±2.89	< 0.001
0	51 (1.9)	6 (0.3)	45 (4.9)	< 0.001
1	10 (0.4)	4 (0.2)	6 (0.7)
2	985 (36.4)	550 (30.7)	435 (47.8)
≥ 3	1,658 (61.3)	1,234 (68.8)	424 (46.6)
Comorbidity
Congestive heart failure	76 (2.8)	59 (3.3)	17 (1.9)	0.04
Hemiplegia or paraplegia	10 (0.4)	6 (0.3)	4 (0.4)	0.74
Dementia	58 (2.1)	46 (2.6)	12 (1.3)	0.04
Chronic pulmonary disease	439 (16.2)	308 (17.2)	131 (14.4)	0.07
Rheumatologic disease	62 (2.3)	38 (2.1)	24 (2.6)	0.39
Diabetes with chronic complication	135 (5.0)	101 (5.6)	34 (3.7)	0.03
Renal disease	45 (1.7)	34 (1.9)	11 (1.2)	0.19
Any malignancy, incl. leukemia and lymphoma	2,631 (97.3)	1,783 (99.4)	848 (93.2)	< 0.001
Metastatic solid tumor	1,115 (41.2)	888 (49.5)	227 (24.9)	< 0.001
Mild liver disease	458 (16.9)	345 (19.2)	113 (12.4)	< 0.001
Moderate or severe liver disease	3 (0.1)	2 (0.1)	1 (0.1)	> 0.99
Treatment modality in LoT 1
RT→SACT	14 (0.5)	14 (0.8)	0	< 0.001
RT-only	65 (2.4)	65 (3.6)	0
SACT-first	910 (33.7)	0	910 (100)
Surgery→Both RT/SACT	443 (16.4)	443 (24.7)	0
Surgery→RT	285 (10.5)	285 (15.9)	0
Surgery→SACT	424 (15.7)	424 (23.6)	0
Surgery-only	563 (20.8)	563 (31.4)	0
SACT-first^a)
SACT-first with following surgery	115 (4.3)	n/a	115 (12.6)	n/a
SACT-first without following surgery	795 (29.4)	n/a	795 (87.4)
No. of LoTs before 1st line of SACT^b)
Mean±SD	1.14±0.38	1.14±0.38	n/a	n/a
Median (Q1-Q3)	1.00 (1.00-1.00)	1.00 (1.00-1.00)	n/a
Interval time between end of LoT 1 and start of LoT 2^b) (mo)
Mean±SD	16.32±19.17	16.32±19.17	n/a	n/a
Median (Q1-Q3)	9.58 (3.61-21.85)	9.58 (3.61-21.85)	n/a
Patient disposition
Observation duration, mo
Mean±SD	30.95±31.99	30.31±32.56	32.22±30.82	0.14
Median (Q1-Q3)	19.48 (7.29-43.53)	17.71 (6.83-41.46)	23.57 (8.05-46.78)
Reason for end of observation
Death	801 (29.6)	603 (33.6)	198 (21.8)	< 0.001
Occurrence of second primary cancer	367 (13.6)	253 (14.1)	114 (12.5)
End of study (31 December 2022)	1,536 (56.8)	938 (52.3)	598 (65.7)

Values are presented as number (%) unless otherwise indicated. EC, endometrial cancer; LoT, line of therapy; mCCI, Modified Charlson Comorbidity Index; n/a, not applicable; Q1, 25th quartile; Q3, 75th quartile; SACT, systemic anticancer therapy; SD, standard deviation; RT, radiation therapy.

^a) Defined only in advanced EC patients,

^b) Defined only in recurrent EC patients.

Table 2.

Treatment regimen in each line of SACT (class-level)

Regimens^a)	Total	Recurrent	Advanced
First line	2,704	1,794	910
Taxanes+platinum	1,136 (42.0)	754 (42.0)	382 (42.0)
Doxorubicin+platinum	474 (17.5)	381 (21.2)	93 (10.2)
Platinum monotherapy	432 (16.0)	218 (12.2)	214 (23.5)
Other platinum-based combinations	280 (10.4)	193 (10.8)	87 (9.6)
Hormone therapy	191 (7.1)	97 (5.4)	94 (10.3)
Undetermined^b)	79 (2.9)	62 (3.5)	17 (1.9)
Non-platinum monotherapy	78 (2.9)	66 (3.7)	12 (1.3)
Combinations not containing platinum	34 (1.3)	23 (1.3)	11 (1.2)
Second line	837	595	242
Doxorubicin+platinum	215 (25.7)	151 (25.4)	64 (26.4)
Taxanes+platinum	193 (23.1)	127 (21.3)	66 (27.3)
Other platinum-based combinations	177 (21.1)	141 (23.7)	36 (14.9)
Platinum monotherapy	89 (10.6)	56 (9.4)	33 (13.6)
Non-platinum monotherapy	64 (7.6)	49 (8.2)	15 (6.2)
Hormone therapy	46 (5.5)	34 (5.7)	12 (5.0)
Undetermined^b)	42 (5.0)	29 (4.9)	13 (5.4)
Combinations not containing platinum	11 (1.3)	8 (1.3)	3 (1.2)
Third line	305	233	72
Other platinum-based combinations	97 (31.8)	75 (32.2)	22 (30.6)
Doxorubicin+platinum	44 (14.4)	26 (11.2)	18 (25.0)
Taxanes+platinum	44 (14.4)	33 (14.2)	11 (15.3)
Hormone therapy	40 (13.1)	34 (14.6)	6 (8.3)
Platinum monotherapy	40 (13.1)	31 (13.3)	9 (12.5)
Non-platinum monotherapy	27 (8.9)	23 (9.9)	4 (5.6)
Undetermined^b)	10 (3.3)	9 (3.9)	1 (1.4)
Combinations not containing platinum	3 (1.0)	2 (0.9)	1 (1.4)
Fourth line	100	83	17
Other platinum-based combinations	34 (34.0)	27 (32.5)	7 (41.2)
Platinum monotherapy	19 (19.0)	15 (18.1)	4 (23.5)
Hormone therapy	13 (13.0)	13 (15.7)	0
Doxorubicin+platinum	10 (10.0)	8 (9.6)	2 (11.8)
Taxanes+platinum	8 (8.0)	7 (8.4)	1 (5.9)
Undetermined^b)	8 (8.0)	7 (8.4)	1 (5.9)
Non-platinum monotherapy	7 (7.0)	5 (6.0)	2 (11.8)
Combinations not containing platinum	1 (1.0)	1 (1.2)	0

Values are presented as number (%). EC, endometrial cancer; SACT, systemic anticancer therapy.

^a) Regimen order in each LoSACT is listed in a descending order of frequencies within all EC patients,

^b) Patients censored before 30th day since each LoSACT initiation were classified as ‘undetermined.’

Table 3.

Top 10 treatment sequences of SACT among regimens consisting of more than 2 lines of SACT (class-level)

Treatment sequences^a)	No. (%)
Overall study population (n=2,704)
Taxanes+platinum > doxorubicin+platinum	95 (3.5)
Taxanes+platinum > taxanes+platinum	37 (1.4)
Platinum monotherapy > taxanes+platinum	37 (1.4)
Taxanes+platinum > other platinum-based combinations	35 (1.3)
Doxorubicin+platinum > other platinum-based combinations	27 (1.0)
Other platinum-based combinations > other platinum-based combinations	26 (1.0)
Doxorubicin+platinum > taxanes+platinum	23 (0.9)
Platinum monotherapy > platinum monotherapy	22 (0.8)
Taxanes+platinum > doxorubicin+platinum > other platinum-based combinations	22 (0.8)
Taxanes+platinum > undetermined^b)	17 (0.6)
Recurrent study population (n=1,794)
Taxanes+platinum > doxorubicin+platinum	60 (3.3)
Taxanes+platinum > taxanes+platinum	27 (1.5)
Doxorubicin+platinum > other platinum-based combinations	26 (1.4)
Taxanes+platinum > other platinum-based combinations	25 (1.4)
Other platinum-based combinations > other platinum-based combinations	18 (1.0)
Doxorubicin+platinum > taxanes+platinum	16 (0.9)
Taxanes+platinum > doxorubicin+platinum > other platinum-based combinations	15 (0.8)
Doxorubicin+platinum > platinum monotherapy	14 (0.8)
Platinum monotherapy > doxorubicin+platinum	13 (0.7)
Platinum monotherapy > taxanes+platinum	13 (0.7)
Advanced study population (n=910)
Taxanes+platinum > doxorubicin+platinum	35 (3.8)
Platinum monotherapy > taxanes+platinum	24 (2.6)
Platinum monotherapy > platinum monotherapy	15 (1.6)
Taxanes+platinum > taxanes+platinum	10 (1.1)
Taxanes+platinum > other platinum-based combinations	10 (1.1)
Other platinum-based combinations > other platinum-based combinations	8 (0.9)
Taxanes+platinum > undetermined^b)	8 (0.9)
Doxorubicin+platinum > taxanes+platinum	7 (0.8)
Taxanes+platinum > doxorubicin+platinum > other platinum-based combinations	7 (0.8)
Taxanes+platinum > non-platinum monotherapy	6 (0.7)

All treatment sequences with frequency less than 3 were presented as ‘others.’ SACT, systemic anticancer therapy.

^a) Sequence order is listed in a descending order of frequencies within recurrent or advanced EC. ‘>’ indicates the progression to the next consecutive line of SACT,

^b) Patients censored before 30th day since each SACT line initiation were classified as ‘undetermined.’

Table 4.

All-cause HCRU attributable to each line of therapy for recurrent or advanced EC

Line of SACT	1st line			2nd line			3rd line
Line of SACT	Total (n=2,704)	Recurrent (n=1,794)	Advanced (n=910)	Total (n=837)	Recurrent (n=595)	Advanced (n=242)	Total (n=305)	Recurrent (n=233)	Advanced (n=72)
No. of inpatient hospitalizations, PPPM
Presence of ≥ 1 inpatient hospitalization	2,444	1,653	791	774	558	216	283	215	68
Median (Q1-Q3)	0.58 (0.18-1.23)	0.65 (0.21-1.28)	0.46 (0.13-1.12)	0.97 (0.41-1.40)	0.99 (0.44-1.39)	0.94 (0.36-1.41)	1.04 (0.56-1.45)	1.10 (0.57-1.45)	0.97 (0.53-1.48)
No. of outpatient visits, PPPM
Presence of ≥ 1 outpatient visits	2,648	1,757	891	804	574	230	293	222	71
Median (Q1-Q3)	3.25 (2.12-4.96)	3.21 (2.13-4.90)	3.32 (2.11-5.04)	3.12 (1.79-4.83)	3.21 (1.83-4.95)	2.87 (1.76-4.53)	2.95 (1.69-4.64)	3.02 (1.73-4.65)	2.60 (1.60-4.64)
No. of ED visits, PPPM
Presence of ≥ 1 ED visits	1,267	866	401	407	287	120	162	117	45
Median (Q1-Q3)	0.13 (0.05-0.33)	0.15 (0.06-0.35)	0.08 (0.04-0.25)	0.23 (0.08-0.47)	0.23 (0.08-0.44)	0.23 (0.08-0.51)	0.32 (0.13-0.72)	0.32 (0.14-0.71)	0.31 (0.08-0.74)
Length of stay (days per admission)
Presence of ≥ 1 inpatient hospitalization	2,444	1,653	791	774	558	216	283	215	68
No. of admissions	17,423	12,085	5,338	5,171	3,854	1,317	1,835	1,296	539
Median (Q1-Q3)	3.00 (2.00-7.00)	3.00 (2.00-7.00)	3.00 (2.00-8.00)	4.00 (2.00-9.00)	4.00 (2.00-9.00)	4.00 (2.00-9.00)	5.00 (2.00-10.00)	5.00 (2.00-10.00)	4.00 (2.00-9.00)

EC, endometrial cancer; ED, emergency department; HCRU, healthcare resource utilization; PPPM, per-patient-per-month; Q1, 25th quartile; Q3, 75th quartile; SACT, systemic anticancer therapy.

REFERENCES

1. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74:229–63. Article PubMed
2. Lim MC, Won YJ, Ko MJ, Kim M, Shim SH, Suh DH, et al. Incidence of cervical, endometrial, and ovarian cancer in Korea during 1999-2015. J Gynecol Oncol. 2019;30:e38Article PubMed PMC PDF
3. Ha HI, Chang HK, Park SJ, Lim J, Won YJ, Lim MC. The incidence and survival of cervical, ovarian, and endometrial cancer in Korea, 1999-2017: Korea Central Cancer Registry. Obstet Gynecol Sci. 2021;64:444–53. Article PubMed PMC PDF
4. Jung KW, Kang MJ, Park EH, Yun EH, Kim HJ, Kim JE, et al. Prediction of Cancer Incidence and Mortality in Korea, 2024. Cancer Res Treat. 2024;56:372–9. Article PubMed PMC PDF
5. Felix AS, Bower JK, Pfeiffer RM, Raman SV, Cohn DE, Sherman ME. High cardiovascular disease mortality after endometrial cancer diagnosis: results from the Surveillance, Epidemiology, and End Results (SEER) Database. Int J Cancer. 2017;140:555–64. Article PubMed PDF
6. Fung-Kee-Fung M, Dodge J, Elit L, Lukka H, Chambers A, Oliver T, et al. Follow-up after primary therapy for endometrial cancer: a systematic review. Gynecol Oncol. 2006;101:520–9. Article PubMed
7. Rutten H, Verhoef C, van Weelden WJ, Smits A, Dhanis J, Ottevanger N, et al. Recurrent Endometrial Cancer: Local and Systemic Treatment Options. Cancers (Basel). 2021;13:6275.Article PubMed PMC
8. Oaknin A, Bosse TJ, Creutzberg CL, Giornelli G, Harter P, Joly F, et al. Endometrial cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022;33:860–77. Article PubMed
9. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: uterine neoplasms. version 2.2024. National Comprehensive Cancer Network; 2024.
10. Makker V, Green AK, Wenham RM, Mutch D, Davidson B, Miller DS. New therapies for advanced, recurrent, and metastatic endometrial cancers. Gynecol Oncol Res Pract. 2017;4:19.Article PubMed PMC PDF
11. Oaknin A, Gilbert L, Tinker AV, Brown J, Mathews C, Press J, et al. Safety and antitumor activity of dostarlimab in patients with advanced or recurrent DNA mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) or proficient/stable (MMRp/MSS) endometrial cancer: interim results from GARNET-a phase I, single-arm study. J Immunother Cancer. 2022;10:e003777Article PubMed PMC
12. Powell MA, Bjorge L, Willmott L, Novak Z, Black D, Gilbert L, et al. Overall survival in patients with endometrial cancer treated with dostarlimab plus carboplatin-paclitaxel in the randomized ENGOT-EN6/GOG-3031/RUBY trial. Ann Oncol. 2024;35:728–38. Article PubMed
13. Heffernan K, Nikitas FS, Shukla U, Camejo HS, Knott C. Previously treated recurrent or advanced endometrial cancer in England: a real-world observational analysis. Gynecol Oncol. 2022;166:317–25. Article PubMed
14. Nwankwo C, Shah R, Shah A, Corman S, Kebede N. Treatment patterns and economic burden among newly diagnosed cervical and endometrial cancer patients. Future Oncol. 2022;18:965–77. Article PubMed
15. Suidan RS, He W, Sun CC, Zhao H, Smith GL, Klopp AH, et al. National trends, outcomes, and costs of radiation therapy in the management of low- and high-intermediate risk endometrial cancer. Gynecol Oncol. 2019;152:439–44. Article PubMed PMC
16. Kim S, Kim MS, You SH, Jung SY. Conducting and reporting a clinical research using Korean Healthcare Claims Database. Korean J Fam Med. 2020;41:146–52. Article PubMed PMC PDF
17. Song SO, Jung CH, Song YD, Park CY, Kwon HS, Cha BS, et al. Background and data configuration process of a nationwide population-based study using the Korean National Health Insurance System. Diabetes Metab J. 2014;38:395–403. Article PubMed PMC
18. Quan H, Li B, Couris CM, Fushimi K, Graham P, Hider P, et al. Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. Am J Epidemiol. 2011;173:676–82. Article PubMed
19. Quan H, Sundararajan V, Halfon P, Fong A, Burnand B, Luthi JC, et al. Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care. 2005;43:1130–9. Article PubMed
20. Park EH, Jung KW, Park NJ, Kang MJ, Yun EH, Kim HJ, et al. Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2021. Cancer Res Treat. 2024;56:357–71. Article PubMed PMC PDF
21. Lai YL, Chiang CJ, Chen YL, You SL, Chen YY, Chiang YC, et al. Increased risk of second primary malignancies among endometrial cancer survivors receiving surgery alone: a population-based analysis. Cancer Med. 2021;10:6845–54. Article PubMed PMC PDF
22. Wang Y, Cai Y. Association between radiation therapy for primary endometrial cancer and risk of second primary malignancies: a retrospective cohort study. Sci Rep. 2024;14:24623.Article PubMed PMC PDF
23. Miller DS, Filiaci VL, Mannel RS, Cohn DE, Matsumoto T, Tewari KS, et al. Carboplatin and paclitaxel for advanced endometrial cancer: final overall survival and adverse event analysis of a phase III trial (NRG Oncology/GOG0209). J Clin Oncol. 2020;38:3841–50. Article PubMed PMC
24. Liu J, Emond B, Maiese EM, Lafeuille MH, Lefebvre P, Ghelerter I, et al. Real-world utilization and outcomes of systemic therapy among patients with advanced or recurrent endometrial cancer in the United States. Curr Med Res Opin. 2022;38:1935–45. Article PubMed
25. Makker V, Hensley ML, Zhou Q, Iasonos A, Aghajanian CA. Treatment of advanced or recurrent endometrial carcinoma with doxorubicin in patients progressing after paclitaxel/carboplatin: Memorial Sloan-Kettering Cancer Center experience from 1995 to 2009. Int J Gynecol Cancer. 2013;23:929–34. PubMed PMC
26. Makker V, Colombo N, Herraez AC, Santin A, Colomba E, Miller D, et al. A multicenter, open-label, randomized, phase III study to compare the efficacy and safety of lenvatinib in combination with pembrolizumab versus treatment of physician’s choice in patients with advanced endometrial cancer. Gynecol Oncol. 2021;162(Suppl 1):S4.Article
27. Lincoln S, Blessing JA, Lee RB, Rocereto TF. Activity of paclitaxel as second-line chemotherapy in endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2003;88:277–81. Article PubMed
28. Coleman RL, Garside J, Hurteau J, Nguyen J, Kobayashi M. Treatment patterns and outcomes among patients with advanced or recurrent endometrial cancer initiating first-line therapy in the United States. J Health Econ Outcomes Res. 2023;10:82–90. Article PubMed PMC
29. O’Malley DM, Bariani GM, Cassier PA, Marabelle A, Hansen AR, De Jesus Acosta A, et al. Pembrolizumab in patients with microsatellite instability-high advanced endometrial cancer: results from the KEYNOTE-158 study. J Clin Oncol. 2022;40:752–61. Article PubMed PMC
30. Makker V, Colombo N, Casado Herraez A, Santin AD, Colomba E, Miller DS, et al. Lenvatinib plus pembrolizumab for advanced endometrial cancer. N Engl J Med. 2022;386:437–48. Article PubMed PMC

Figure & Data

REFERENCES

Citations

Citations to this article as recorded by

PubReader
ePub Link

Cite

CITE: export Copy Download Format; Close

Download Citation

Download a citation file in RIS format that can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Reference Manager.

Format:

RIS — For EndNote, ProCite, RefWorks, and most other reference management software
BibTeX — For JabRef, BibDesk, and other BibTeX-specific software

Include:

Citation for the content below
Citation and abstract for the content below

Disease Burden and Treatment Pattern of Advanced or Recurrent Endometrial Cancer in Korea: A Nationwide Database (DIRECTION) Study

DOI: https://doi.org/10.4143/crt.2025.065

XML Download

Abstract
Introduction
Materials and Methods
Results
Discussion
Electronic Supplementary Material
NOTES
REFERENCES

Implementation of BRCA Test among Young Breast Cancer Patients in South Korea: A Nationwide Cohort Study

Disease Burden and Treatment Pattern of Advanced or Recurrent Endometrial Cancer in Korea: A Nationwide Database (DIRECTION) Study

Fig. 1. Flow chart of study population selection. EC, endometrial cancer; LoT, line of therapy; RT, radiotherapy; SACT, systemic anticancer therapy.

Fig. 2. Treatment sequence of systemic anticancer therapy (SACT) for overall endometrial cancer patients (sunburst plot).

Fig. 3. Kaplan-Meier curves for systemic anticancer therapy (SACT)–free interval time (A) and time to next treatment (B). EC, endometrial cancer.

Fig. 4. All-cause (A) and endometrial cancer (EC)–related (B) costs attributable to each line of therapy for recurrent or advanced EC.

Fig. 1.

Fig. 2.

Fig. 3.

Fig. 4.

Disease Burden and Treatment Pattern of Advanced or Recurrent Endometrial Cancer in Korea: A Nationwide Database (DIRECTION) Study

	Total	Recurrent	Advanced	p-value
Demographic characteristic
Age at diagnosis index date (yr)
19-29	34 (1.3)	20 (1.1)	14 (1.5)	0.06
30-39	117 (4.3)	78 (4.3)	39 (4.3)
40-49	339 (12.5)	208 (11.6)	131 (14.4)
50-59	1,122 (41.5)	734 (40.9)	388 (42.6)
60-69	798 (29.5)	551 (30.7)	247 (27.1)
70-79	258 (9.5)	183 (10.2)	75 (8.2)
≥ 80	36 (1.3)	20 (1.1)	16 (1.8)
Age at index date of 1st line of SACT (yr)
19-29	29 (1.1)	15 (0.8)	14 (1.5)	< 0.001
30-39	95 (3.5)	60 (3.3)	35 (3.8)
40-49	304 (11.2)	178 (9.9)	126 (13.8)
50-59	1,030 (38.1)	648 (36.1)	382 (42.0)
60-69	882 (32.6)	625 (34.8)	257 (28.2)
70-79	318 (11.8)	240 (13.4)	78 (8.6)
≥ 80	46 (1.7)	28 (1.6)	18 (2.0)
Insurance type
Health insurance	2,601 (96.2)	1,726 (96.2)	875 (96.2)	0.94
Medical aid	103 (3.8)	68 (3.8)	35 (3.8)
Institution type
General hospital	2,694 (99.6)	1,788 (99.7)	906 (99.6)	0.67
Hospital	9 (0.3)	5 (0.3)	4 (0.4)
Clinic	1 (0)	1 (0.1)	0
Institution region
Metropolitan area (Seoul, Gyeonggi, Incheon)	1,856 (68.6)	1,262 (70.3)	594 (65.3)	< 0.001
Gangwon	39 (1.4)	22 (1.2)	17 (1.9)
Gyoengsang	586 (21.7)	348 (19.4)	238 (26.2)
Chungcheong (including Sejong)	122 (4.5)	86 (4.8)	36 (4.0)
Jeolla (including Jeju)	101 (3.7)	76 (4.2)	25 (2.7)
Calendar year of EC diagnosis
2010	123 (4.5)	100 (5.6)	23 (2.5)	< 0.001
2011	143 (5.3)	107 (6.0)	36 (4.0)
2012	154 (5.7)	124 (6.9)	30 (3.3)
2013	159 (5.9)	135 (7.5)	24 (2.6)
2014	162 (6.0)	133 (7.4)	29 (3.2)
2015	195 (7.2)	157 (8.8)	38 (4.2)
2016	225 (8.3)	163 (9.1)	62 (6.8)
2017	252 (9.3)	168 (9.4)	84 (9.2)
2018	303 (11.2)	204 (11.4)	99 (10.9)
2019	306 (11.3)	179 (10.0)	127 (14.0)
2020	299 (11.1)	161 (9.0)	138 (15.2)
2021	236 (8.7)	121 (6.7)	115 (12.6)
2022	147 (5.4)	42 (2.3)	105 (11.5)
Calendar year of 1st line of SACT initiation
2010	34 (1.3)	17 (0.9)	17 (1.9)	< 0.001
2011	91 (3.4)	61 (3.4)	30 (3.3)
2012	99 (3.7)	72 (4.0)	27 (3.0)
2013	118 (4.4)	96 (5.4)	22 (2.4)
2014	130 (4.8)	104 (5.8)	26 (2.9)
2015	133 (4.9)	102 (5.7)	31 (3.4)
2016	151 (5.6)	101 (5.6)	50 (5.5)
2017	264 (9.8)	185 (10.3)	79 (8.7)
2018	287 (10.6)	183 (10.2)	104 (11.4)
2019	335 (12.4)	216 (12.0)	119 (13.1)
2020	366 (13.5)	212 (11.8)	154 (16.9)
2021	333 (12.3)	215 (12.0)	118 (13.0)
2022	363 (13.4)	230 (12.8)	133 (14.6)
Clinical characteristic
mCCI
Mean±SD	5.12±3.26	5.74±3.26	3.91±2.89	< 0.001
0	51 (1.9)	6 (0.3)	45 (4.9)	< 0.001
1	10 (0.4)	4 (0.2)	6 (0.7)
2	985 (36.4)	550 (30.7)	435 (47.8)
≥ 3	1,658 (61.3)	1,234 (68.8)	424 (46.6)
Comorbidity
Congestive heart failure	76 (2.8)	59 (3.3)	17 (1.9)	0.04
Hemiplegia or paraplegia	10 (0.4)	6 (0.3)	4 (0.4)	0.74
Dementia	58 (2.1)	46 (2.6)	12 (1.3)	0.04
Chronic pulmonary disease	439 (16.2)	308 (17.2)	131 (14.4)	0.07
Rheumatologic disease	62 (2.3)	38 (2.1)	24 (2.6)	0.39
Diabetes with chronic complication	135 (5.0)	101 (5.6)	34 (3.7)	0.03
Renal disease	45 (1.7)	34 (1.9)	11 (1.2)	0.19
Any malignancy, incl. leukemia and lymphoma	2,631 (97.3)	1,783 (99.4)	848 (93.2)	< 0.001
Metastatic solid tumor	1,115 (41.2)	888 (49.5)	227 (24.9)	< 0.001
Mild liver disease	458 (16.9)	345 (19.2)	113 (12.4)	< 0.001
Moderate or severe liver disease	3 (0.1)	2 (0.1)	1 (0.1)	> 0.99
Treatment modality in LoT 1
RT→SACT	14 (0.5)	14 (0.8)	0	< 0.001
RT-only	65 (2.4)	65 (3.6)	0
SACT-first	910 (33.7)	0	910 (100)
Surgery→Both RT/SACT	443 (16.4)	443 (24.7)	0
Surgery→RT	285 (10.5)	285 (15.9)	0
Surgery→SACT	424 (15.7)	424 (23.6)	0
Surgery-only	563 (20.8)	563 (31.4)	0
SACT-first^a)
SACT-first with following surgery	115 (4.3)	n/a	115 (12.6)	n/a
SACT-first without following surgery	795 (29.4)	n/a	795 (87.4)
No. of LoTs before 1st line of SACT^b)
Mean±SD	1.14±0.38	1.14±0.38	n/a	n/a
Median (Q1-Q3)	1.00 (1.00-1.00)	1.00 (1.00-1.00)	n/a
Interval time between end of LoT 1 and start of LoT 2^b) (mo)
Mean±SD	16.32±19.17	16.32±19.17	n/a	n/a
Median (Q1-Q3)	9.58 (3.61-21.85)	9.58 (3.61-21.85)	n/a
Patient disposition
Observation duration, mo
Mean±SD	30.95±31.99	30.31±32.56	32.22±30.82	0.14
Median (Q1-Q3)	19.48 (7.29-43.53)	17.71 (6.83-41.46)	23.57 (8.05-46.78)
Reason for end of observation
Death	801 (29.6)	603 (33.6)	198 (21.8)	< 0.001
Occurrence of second primary cancer	367 (13.6)	253 (14.1)	114 (12.5)
End of study (31 December 2022)	1,536 (56.8)	938 (52.3)	598 (65.7)

Regimens^a)	Total	Recurrent	Advanced
First line	2,704	1,794	910
Taxanes+platinum	1,136 (42.0)	754 (42.0)	382 (42.0)
Doxorubicin+platinum	474 (17.5)	381 (21.2)	93 (10.2)
Platinum monotherapy	432 (16.0)	218 (12.2)	214 (23.5)
Other platinum-based combinations	280 (10.4)	193 (10.8)	87 (9.6)
Hormone therapy	191 (7.1)	97 (5.4)	94 (10.3)
Undetermined^b)	79 (2.9)	62 (3.5)	17 (1.9)
Non-platinum monotherapy	78 (2.9)	66 (3.7)	12 (1.3)
Combinations not containing platinum	34 (1.3)	23 (1.3)	11 (1.2)
Second line	837	595	242
Doxorubicin+platinum	215 (25.7)	151 (25.4)	64 (26.4)
Taxanes+platinum	193 (23.1)	127 (21.3)	66 (27.3)
Other platinum-based combinations	177 (21.1)	141 (23.7)	36 (14.9)
Platinum monotherapy	89 (10.6)	56 (9.4)	33 (13.6)
Non-platinum monotherapy	64 (7.6)	49 (8.2)	15 (6.2)
Hormone therapy	46 (5.5)	34 (5.7)	12 (5.0)
Undetermined^b)	42 (5.0)	29 (4.9)	13 (5.4)
Combinations not containing platinum	11 (1.3)	8 (1.3)	3 (1.2)
Third line	305	233	72
Other platinum-based combinations	97 (31.8)	75 (32.2)	22 (30.6)
Doxorubicin+platinum	44 (14.4)	26 (11.2)	18 (25.0)
Taxanes+platinum	44 (14.4)	33 (14.2)	11 (15.3)
Hormone therapy	40 (13.1)	34 (14.6)	6 (8.3)
Platinum monotherapy	40 (13.1)	31 (13.3)	9 (12.5)
Non-platinum monotherapy	27 (8.9)	23 (9.9)	4 (5.6)
Undetermined^b)	10 (3.3)	9 (3.9)	1 (1.4)
Combinations not containing platinum	3 (1.0)	2 (0.9)	1 (1.4)
Fourth line	100	83	17
Other platinum-based combinations	34 (34.0)	27 (32.5)	7 (41.2)
Platinum monotherapy	19 (19.0)	15 (18.1)	4 (23.5)
Hormone therapy	13 (13.0)	13 (15.7)	0
Doxorubicin+platinum	10 (10.0)	8 (9.6)	2 (11.8)
Taxanes+platinum	8 (8.0)	7 (8.4)	1 (5.9)
Undetermined^b)	8 (8.0)	7 (8.4)	1 (5.9)
Non-platinum monotherapy	7 (7.0)	5 (6.0)	2 (11.8)
Combinations not containing platinum	1 (1.0)	1 (1.2)	0

Treatment sequences^a)	No. (%)
Overall study population (n=2,704)
Taxanes+platinum > doxorubicin+platinum	95 (3.5)
Taxanes+platinum > taxanes+platinum	37 (1.4)
Platinum monotherapy > taxanes+platinum	37 (1.4)
Taxanes+platinum > other platinum-based combinations	35 (1.3)
Doxorubicin+platinum > other platinum-based combinations	27 (1.0)
Other platinum-based combinations > other platinum-based combinations	26 (1.0)
Doxorubicin+platinum > taxanes+platinum	23 (0.9)
Platinum monotherapy > platinum monotherapy	22 (0.8)
Taxanes+platinum > doxorubicin+platinum > other platinum-based combinations	22 (0.8)
Taxanes+platinum > undetermined^b)	17 (0.6)
Recurrent study population (n=1,794)
Taxanes+platinum > doxorubicin+platinum	60 (3.3)
Taxanes+platinum > taxanes+platinum	27 (1.5)
Doxorubicin+platinum > other platinum-based combinations	26 (1.4)
Taxanes+platinum > other platinum-based combinations	25 (1.4)
Other platinum-based combinations > other platinum-based combinations	18 (1.0)
Doxorubicin+platinum > taxanes+platinum	16 (0.9)
Taxanes+platinum > doxorubicin+platinum > other platinum-based combinations	15 (0.8)
Doxorubicin+platinum > platinum monotherapy	14 (0.8)
Platinum monotherapy > doxorubicin+platinum	13 (0.7)
Platinum monotherapy > taxanes+platinum	13 (0.7)
Advanced study population (n=910)
Taxanes+platinum > doxorubicin+platinum	35 (3.8)
Platinum monotherapy > taxanes+platinum	24 (2.6)
Platinum monotherapy > platinum monotherapy	15 (1.6)
Taxanes+platinum > taxanes+platinum	10 (1.1)
Taxanes+platinum > other platinum-based combinations	10 (1.1)
Other platinum-based combinations > other platinum-based combinations	8 (0.9)
Taxanes+platinum > undetermined^b)	8 (0.9)
Doxorubicin+platinum > taxanes+platinum	7 (0.8)
Taxanes+platinum > doxorubicin+platinum > other platinum-based combinations	7 (0.8)
Taxanes+platinum > non-platinum monotherapy	6 (0.7)

Line of SACT	1st line			2nd line			3rd line
Line of SACT	Total (n=2,704)	Recurrent (n=1,794)	Advanced (n=910)	Total (n=837)	Recurrent (n=595)	Advanced (n=242)	Total (n=305)	Recurrent (n=233)	Advanced (n=72)
No. of inpatient hospitalizations, PPPM
Presence of ≥ 1 inpatient hospitalization	2,444	1,653	791	774	558	216	283	215	68
Median (Q1-Q3)	0.58 (0.18-1.23)	0.65 (0.21-1.28)	0.46 (0.13-1.12)	0.97 (0.41-1.40)	0.99 (0.44-1.39)	0.94 (0.36-1.41)	1.04 (0.56-1.45)	1.10 (0.57-1.45)	0.97 (0.53-1.48)
No. of outpatient visits, PPPM
Presence of ≥ 1 outpatient visits	2,648	1,757	891	804	574	230	293	222	71
Median (Q1-Q3)	3.25 (2.12-4.96)	3.21 (2.13-4.90)	3.32 (2.11-5.04)	3.12 (1.79-4.83)	3.21 (1.83-4.95)	2.87 (1.76-4.53)	2.95 (1.69-4.64)	3.02 (1.73-4.65)	2.60 (1.60-4.64)
No. of ED visits, PPPM
Presence of ≥ 1 ED visits	1,267	866	401	407	287	120	162	117	45
Median (Q1-Q3)	0.13 (0.05-0.33)	0.15 (0.06-0.35)	0.08 (0.04-0.25)	0.23 (0.08-0.47)	0.23 (0.08-0.44)	0.23 (0.08-0.51)	0.32 (0.13-0.72)	0.32 (0.14-0.71)	0.31 (0.08-0.74)
Length of stay (days per admission)
Presence of ≥ 1 inpatient hospitalization	2,444	1,653	791	774	558	216	283	215	68
No. of admissions	17,423	12,085	5,338	5,171	3,854	1,317	1,835	1,296	539
Median (Q1-Q3)	3.00 (2.00-7.00)	3.00 (2.00-7.00)	3.00 (2.00-8.00)	4.00 (2.00-9.00)	4.00 (2.00-9.00)	4.00 (2.00-9.00)	5.00 (2.00-10.00)	5.00 (2.00-10.00)	4.00 (2.00-9.00)

Table 1. Patient characteristics among recurrent or advanced EC patients

Defined only in advanced EC patients,

Defined only in recurrent EC patients.

Table 2. Treatment regimen in each line of SACT (class-level)

Values are presented as number (%). EC, endometrial cancer; SACT, systemic anticancer therapy.

Regimen order in each LoSACT is listed in a descending order of frequencies within all EC patients,

Patients censored before 30th day since each LoSACT initiation were classified as ‘undetermined.’

Table 3. Top 10 treatment sequences of SACT among regimens consisting of more than 2 lines of SACT (class-level)

All treatment sequences with frequency less than 3 were presented as ‘others.’ SACT, systemic anticancer therapy.

Sequence order is listed in a descending order of frequencies within recurrent or advanced EC. ‘>’ indicates the progression to the next consecutive line of SACT,

Patients censored before 30th day since each SACT line initiation were classified as ‘undetermined.’

Table 4. All-cause HCRU attributable to each line of therapy for recurrent or advanced EC

EC, endometrial cancer; ED, emergency department; HCRU, healthcare resource utilization; PPPM, per-patient-per-month; Q1, 25th quartile; Q3, 75th quartile; SACT, systemic anticancer therapy.