Determination of prognostic factors and optimal adjuvant therapy in patients with FIGO stage III endometrial cancer—a multi-institutional cohort study

Background: This study aimed to identify prognostic factors and assess which high-risk subgroups would benefit the most from the combination of chemotherapy and radiotherapy in patients with stage III endometrial cancer. Methods: A retrospective analysis was conducted with a cohort of 294 patients diagnosed with stage III endometrial cancer. All of whom underwent comprehensive surgical staging and adjuvant treatment between 2009 and 2021. Results: The median follow-up period was 42 months. Age over 60 years, substage IIIC2, and high grade or non-endometrioid histology were associated with poorer cancer-specific and overall survival (OS), though only age over 60 emerged as an independent adverse prognostic factor. Across the full cohort, survival did not differ significantly by adjuvant treatment modality. However, among patients aged over 60 years, adjuvant radiotherapy alone was associated with the lowest 5-year OS (42.3%), compared to chemotherapy alone (53.4%) and combined chemoradiotherapy (68.7%). In multivariate analysis, patients in this age group who received radiotherapy alone had significantly worse OS compared to those who received combined chemotherapy and radiotherapy (hazard ratio (HR) 3.15, 95% confidence interval (CI): 1.05–9.47, p = 0.04). Conclusions: The result of this real-world, multi-institutional cohort study showed that age over 60 years was a poor prognostic factor for stage III endometrial cancer patients. Combining adjuvant chemotherapy with radiotherapy was associated with the best survival outcomes, but this was only significant for patients aged over 60 years. Further prospective investigations of adjuvant therapies are warranted.

Adjuvant therapy; Elderly; Endometrial cancer; Prognostic factor; Stage III

[1] Taiwan Cancer Registry Task Force. Taiwan cancer registry annual report. 2022. Available at: https://www.hpa.gov.tw/Pages/List.aspx?nodeid=269 (Accessed: 18 March 2025).

[2] de Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C, et al. Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial. The Lancet Oncology. 2019; 20: 1273–1285.

[3] Matei D, Filiaci V, Randall ME, Mutch D, Steinhoff MM, DiSilvestro PA, et al. Adjuvant chemotherapy plus radiation for locally advanced endometrial cancer. The New England Journal of Medicine. 2019; 380: 2317–2326.

[4] Matei D, Enserro D, Kudrimoti M, Steinhoff M, DiSilvestro P, Walker J, et al. Overall survival in NRG258, a randomized phase III trial of chemo-radiation vs. chemotherapy alone for locally advanced endometrial carcinoma (LBA 5). Gynecologic Oncology. 2023; 176: S30–S31.

[5] Yoo JG, Kim JH, Kim CJ, Lee HN, Song MJ, Park DC, et al. Postoperative adjuvant chemoradiotherapy versus chemotherapy alone for stage III endometrial cancer: a multicenter retrospective study. Cancer Control. 2022; 29: 10732748221115288.

[6] Zhang G, Li H, Tian Z, Li X, Wang Z, Liang X, et al. Adjuvant chemoradiotherapy versus chemotherapy alone in stage III endometrial cancer: a systematic review and meta-analysis. Journal of Obstetrics and Gynaecology Research. 2022; 48: 1888–1896.

[7] Cao SY, Fan Y, Zhang YF, Ruan JY, Mu Y, Li JK. Recurrence and survival of patients with stage III endometrial cancer after radical surgery followed by adjuvant chemo- or chemoradiotherapy: a systematic review and meta-analysis. BMC Cancer. 2023; 23: 31.

[8] van Weelden WJ, Reijnen C, Eggink FA, Boll D, Ottevanger PB, van den Berg HA, et al. Impact of different adjuvant treatment approaches on survival in stage III endometrial cancer: a population-based study. European Journal of Cancer. 2020; 133: 104–111.

[9] Pecorelli S. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. International Journal of Gynecology & Obstetrics. 2009; 105: 103–104.

[10] Harkenrider MM, Abu-Rustum N, Albuquerque K, Bradfield L, Bradley K, Dolinar E, et al. Radiation therapy for endometrial cancer: an american society for radiation oncology clinical practice guideline. Practical Radiation Oncology. 2023; 13: 41–65.

[11] Mayama M, Asano H, Nomura E, Ihira K, Nozaki A, Kato T, et al. Four versus six chemotherapy cycles in endometrial carcinoma with a high risk of recurrence: a retrospective study. Japanese Journal of Clinical Oncology. 2020; 50: 882–888.

[12] Kahramanoglu I, Meydanli MM, Taranenka S, Ayhan A, Salman C, Sanci M, et al. SATEN III—Splitting Adjuvant Treatment of stage III ENdometrial cancers: an international, multicenter study. International Journal of Gynecological Cancer. 2019; 29: 1271–1279.

[13] Xiang M, English DP, Kidd EA. Defining the survival benefit of adjuvant pelvic radiotherapy and chemotherapy versus chemotherapy alone in stages III–IVA endometrial carcinoma. Gynecologic Oncology. 2019; 154: 487–494.

[14] Priyadarshini S, Swain PK, Padhee S, Agarwal K. Cause-specific survival analysis of gynecological cancers among a non-White population: a SEER-based study. American Journal of Epidemiology. 2025; 194: 95–102.

[15] Clark LH, Jackson AL, Gehrig PA, Bae-Jump V, Van Le L, Ko EM. Adjuvant treatment and clinical trials in elderly patients with endometrial cancer: a time for change? International Journal of Gynecological Cancer. 2016; 26: 282–289.

[16] Eggemann H, Ignatov T, Burger E, Costa SD, Ignatov A. Management of elderly women with endometrial cancer. Gynecologic Oncology. 2017; 146: 519–524.

[17] Forte M, Cecere SC, Di Napoli M, Ventriglia J, Tambaro R, Rossetti S, et al. Endometrial cancer in the elderly: characteristics, prognostic and risk factors, and treatment options. Critical Reviews in Oncology/Hematology. 2024; 204: 104533.

[18] Sarfati D, Blakely T, Pearce N. Measuring cancer survival in populations: relative survival vs cancer-specific survival. International Journal of Epidemiology. 2010; 39: 598–610.

[19] León-Castillo A, de Boer SM, Powell ME, Mileshkin LR, Mackay HJ, Leary A, et al. Molecular classification of the PORTEC-3 trial for high-risk endometrial cancer: impact on prognosis and benefit from adjuvant therapy. Journal of Clinical Oncology. 2020; 38: 3388–3397.

[20] Yang Y, Wu SF, Bao W. Molecular subtypes of endometrial cancer: Implications for adjuvant treatment strategies. International Journal of Gynecology & Obstetrics. 2024; 164: 436–459.

[21] Lin H, Ou YC, Fu HC, Huang SW, Wu CH, Changchien CC. Molecular subtyping and the 2023 FIGO staging in endometrial cancer: redefining adjuvant therapy. Taiwanese Journal of Obstetrics and Gynecology. 2025; 64: 616–624.

[22] Van Gorp T, Cibula D, Lv W, Backes F, Ortaç F, Hasegawa K, et al. ENGOT-en11/GOG-3053/KEYNOTE-B21: a randomised, double-blind, phase III study of pembrolizumab or placebo plus adjuvant chemotherapy with or without radiotherapy in patients with newly diagnosed, high-risk endometrial cancer. Annals of Oncology. 2024; 35: 968–980.