New Long-Term Data Reinforces Chemoradiotherapy Benefit for High-Risk Endometrial Cancer
A decade-long follow-up of the phase 3 PORTEC-3 trial demonstrates that adjuvant chemoradiotherapy significantly improves both overall survival (OS) and recurrence-free survival (RFS) compared to radiotherapy alone for patients with high-risk endometrial cancer. The findings, published in Lancet Oncology (2025;26:1370-1381), build upon previous results and suggest a notably strong benefit for patients with P53-abnormal cancers.
The Dutch Gynaecological Oncology Group-led trial enrolled adult patients with high-risk disease, defined as endometroid-type cancer with specific staging and grade criteria (FIGO 2009 stage I, grade 3 with deep myometrial invasion or lymphovascular space invasion; stage II, IIIA, IIIC, or IIIB endometroid cancer; or stage I, II, or III disease with serous or clear cell histology). Participants were randomized 1:1 to receive either adjuvant chemoradiation or radiotherapy alone,stratified by group,surgery type,FIGO stage,and histology type.
Patients receiving radiotherapy alone were treated with 48.6 Gy of pelvic radiation in 1.8 Gy fractions five times weekly, with a brachytherapy boost for cervical stromal involvement. The chemoradiotherapy arm received the same radiation dose plus two concurrent cycles of 50 mg/m2 intravenous cisplatin during weeks 1 and 4 of radiotherapy, followed by four adjuvant cycles of carboplatin (AUC 5) and intravenous paclitaxel (175 mg/m2) at 3-week intervals.
The median age of patients in both arms was approximately 62 years (radiotherapy: 62.4 years, IQR 56.5-67.9; chemoradiotherapy: 62.0 years, IQR 55.8-68.2). Disease distribution was similar between groups, with most patients having stage II (24% vs 27%) or III (46% vs 43%) disease. Molecular classifications at baseline included MMRd (32% vs 36%), NSMP (32% vs 27%), and P53 abnormal (25% vs 23%). Notably, the study reported a 61.7% (95% CI, 47.0%-73.4%) benefit for NSMP cancers with chemoradiotherapy (adjusted HR, 0.61; 95% CI, 0.33-1.15; P* = 0.13).
“This long-term analysis…supports previous findings of a significant enhancement in both [OS and RFS] with chemoradiotherapy compared with radiotherapy alone for patients with high-risk endometrial cancer,” stated Cathalijne C.B. Post, MD, of Leiden University Medical Center in The Netherlands, and study coinvestigators. “This long-term analysis shows improved 10-year OS and RFS…with most clinically relevant benefit from chemoradiotherapy suggested for[[[[P53* abnormal]cancers.”
The primary endpoints were 10-year OS and RFS, with secondary endpoints including patterns of recurrence and safety. The analysis revealed that most recurrences occurred at distant sites, while local and regional nodal control remained excellent in both treatment groups.
