Surgery plus post-operative radiotherapy versus definitive chemoradiotherapy in locally advanced endocervical adenocarcinoma.

Objective: This study evaluated whether treatment outcomes for endocervical adenocarcinoma differ according to treatment modality (surgery plus post-operative radiotherapy versus definitive chemoradiotherapy) and human papillomavirus (HPV) status.

Methods: We retrospectively analyzed 105 patients with clinical stage IIB to IIIC endocervical adenocarcinoma, classified according to the 2018 International Federation of Gynecology and Obstetrics staging system, who were treated with surgery plus post-operative radiotherapy or definitive chemoradiotherapy at a single institution between 2011 and 2022. HPV status was determined based on the 2020 World Health Organization classification. Among the 105 patients, 61 had HPV-associated tumors and 44 had HPV-independent tumors. Patients were categorized into 4 groups: HPV-associated surgery plus post-operative radiotherapy (n = 46), HPV-associated definitive chemoradiotherapy (n = 15), HPV-independent surgery plus post-operative radiotherapy (n = 27), and HPV-independent definitive chemoradiotherapy (n = 17). Progression-free survival, locoregional recurrence-free survival, and overall survival were evaluated.

Results: Baseline characteristics differed significantly among the 4 groups, particularly in clinical stage, tumor size, and parametrial invasion. The 3-year progression-free, locoregional recurrence-free, and overall survival rates were 47.4%, 54.7%, and 69.8%, respectively. By group, survival rates were 55.4%, 66.4%, and 76.9% for HPV-associated surgery plus post-operative radiotherapy; 52.5%, 52.5%, and 93.3% for HPV-associated definitive chemoradiotherapy; and 54.3%, 56.8%, and 67.5% for HPV-independent surgery plus post-operative radiotherapy, compared with significantly poorer rates of 11.8%, 20.6%, and 33.1% for HPV-independent definitive chemoradiotherapy (p < .05). These differences remained significant after multivariate adjustment, while no significant survival differences were observed between other groups. In a sub-group analysis of HPV-independent patients with clinical T2 to T3 disease, definitive chemoradiotherapy remained associated with worse outcomes than surgery plus post-operative radiotherapy.

Conclusions: Definitive chemoradiotherapy showed outcomes comparable to surgery plus post-operative radiotherapy in HPV-associated adenocarcinoma, but was associated with significantly worse survival in HPV-independent cases. Further studies are warranted to confirm these findings.