Impact of adjuvant radiotherapy on the survival of women with optimally resected stage III endometrial cancer in the era of modern radiotherapy: a retrospective study

Jenny Ling-Yu Chen, Yu-Sen Huang, Chao-Yuan Huang, Che-Yu Hsu, Keng-Hsueh Lan, Wen-Fang Cheng, Sung-Hsin Kuo, Jenny Ling-Yu Chen, Yu-Sen Huang, Chao-Yuan Huang, Che-Yu Hsu, Keng-Hsueh Lan, Wen-Fang Cheng, Sung-Hsin Kuo

Abstract

Background: The optimal adjuvant treatment for stage III endometrial cancer in the era of modern radiotherapy remains undefined. We investigated the benefit of adjuvant radiotherapy for women who underwent optimal resection for stage III endometrial cancer in the era of modern radiotherapy.

Methods: We retrospectively reviewed patients with endometrial cancer who were treated between 2010 and 2018. Adjuvant treatment included radiotherapy by modern radiotherapy techniques (intensity-modulated or volumetric modulated arc radiotherapy), chemotherapy, or both. Recurrence-free survival (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method and analyzed via multivariate Cox proportional hazards models.

Results: One hundred sixty-one patients were initially included (52, 9, and 100 with stages IIIA, IIIB, and IIIC cancer, respectively); 154 patients (96%) received adjuvant therapy. Such adjuvant treatment was associated with improved RFS (p = 0.014) and OS (p = 0.044) over surgery alone. Adjuvant radiotherapy by modern radiotherapy techniques led to low incidence of acute (25%) and chronic (7%) grade ≥ 2 gastrointestinal toxicity. On univariate analysis, non-endometrioid histology and grade 3 status were associated with higher risks of tumor recurrence and death, whereas adjuvant radiotherapy alone or in combination chemotherapy reduced their risks. On multivariate analysis, non-endometrioid histology was associated with increased recurrence (hazard ratio [HR], 2.95; p = 0.009), whereas adjuvant radiotherapy alone or with chemotherapy was associated with lower recurrence (HR, 0.62; p = 0.042). Patients > 60 years of age (p = 0.038) as well as those with endometrioid histology (p = 0.045), lymphovascular space invasion (p = 0.031), and ≥ 2 positive lymph nodes (p = 0.044) benefited most from adjuvant radiotherapy.

Conclusions: Modern adjuvant radiotherapy (intensity-modulated or volumetric modulated arc radiotherapy) alone or with chemotherapy should be considered for women with optimally resected stage III endometrial cancer.

Trial registration: ClinicalTrials.gov, NCT04251676. Registered 24 January 2020. Retrospectively registered.

Keywords: Adjuvant therapy; Endometrial cancer; Intensity-modulated radiotherapy; Stage III; Volumetric modulated arc radiotherapy.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Modern radiotherapy technique and dose distributions. This figure shows the isodose distributions in a patient with optimally resected stage III endometrial cancer who underwent adjuvant radiotherapy via volumetric modulated arc therapy (VMAT). A 50.4-Gy dose (28 fractions) was prescribed to the target volumes. a Beam arrangement according to the VMAT plan. Dose distributions in the axial (b), coronal (c), and sagittal (d) views. The green color-washed areas indicate the target volume (i.e., vagina and nodal lymphatics in the pelvis). The red, blue, green, pink, and indigo lines represent isodose curves of 50.4, 45, 40, 35, and 30 Gy, respectively.
Fig. 2
Fig. 2
Survival in patients with optimally resected stage III endometrial cancer by type of adjuvant treatment (n = 154). Recurrence-free survival (RFS) (a) and overall survival (OS) (b) of patients based on the type of adjuvant treatment: adjuvant chemotherapy (CT) alone, adjuvant radiotherapy (RT) alone, or combined chemoradiotherapy. RFS (c) and OS (d) of patients based on whether or not they received radiotherapy alone or combined with chemotherapy. RFS (e) and OS (f) of patients based on whether or not they received chemotherapy alone or combined with radiotherapy. p-values were determined using Kaplan-Meier log-rank tests.
Fig. 3
Fig. 3
Subgroup analysis of prognostic factors for recurrence-free survival in patients with stage III endometrial cancer (n = 154). The hazard ratios and 95% confidence intervals were calculated using the Cox proportional hazards regression model. LN, lymph node; LVSI, lymphovascular space invasion

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