By Matthew Stenger
Posted: 9/19/2025 9:34:00 AM
Last Updated:
In a preplanned 10-year analysis from the phase III PORTEC-3 trial reported in The Lancet Oncology, Post et al found that adjuvant chemoradiotherapy was associated with improved overall survival and recurrence-free survival vs radiotherapy in women with high-risk endometrial cancer.
Study Details
In the open-label international trial, 660 eligible and evaluable patients were randomly assigned between November 2006 and December 2013 to receive pelvic radiotherapy at 48.6 Gy in 1.8 Gy fractions (n = 330) or chemoradiotherapy with pelvic radiotherapy (same dose/schedule) with two cycles of cisplatin at 50 mg/m² in weeks 1 and 4 followed by four cycles of carboplatin with an AUC of 5 and paclitaxel at 175 mg/m² at 3-week intervals (n = 330). The primary outcome measures were 10-year overall survival and recurrence-free survival in the intention-to-treat population.
Key Findings
Median follow-up was 10.1 years (interquartile range = 9.8–11.0 years).
The estimated 10-year overall survival rate was 74.4% (95% confidence interval [CI] = 69.8%–79.4%) in the chemoradiotherapy group vs 67.3% (95% CI = 62.3%–72.7%) in the radiotherapy group (adjusted hazard ratio [HR] = 0.73, 95% CI = 0.54–0.97, P = .032). The estimated 10-year recurrence-free survival rate was 72.8% (95% CI = 67.2%–77.6%) in the chemoradiotherapy group vs 67.4% (95% CI = 61.7%–72.4%) in the radiotherapy group (adjusted HR = 0.74, 95% CI = 0.56–0.98, P = .034).
Molecular analysis data were available for 210 patients (64%) in the chemoradiotherapy group and 201 patients (61%) in the radiotherapy group. Among patients with p53-abnormal tumors, the 10-year overall survival rate was 52.7% (95% CI = 40.8%–68.1%) in the chemoradiotherapy group vs 36.6% (95% CI = 25.0%–53.7%) in the radiotherapy group (adjusted HR = 0.52, 95% CI = 0.30–0.91, P = .021); the 10-year recurrence-free survival rate was 52.6% (95% CI = 38.3%–65.0%) in the chemoradiotherapy group vs 37.0% (95% CI = 23.7%–50.2%) in the radiotherapy group (HR = 0.42, 95% CI = 0.24–0.74, P = .0027).
Molecular analysis showed no apparent benefit with chemoradiotherapy vs radiotherapy in patients with mismatch repair–deficient cancers or POLE-mutant cancers. Treatment effects for no specific molecular profile cancers appeared to be modulated by estrogen receptor status.
The investigators concluded: “[The] 10-year overall survival and recurrence-free survival were improved for patients with high-risk endometrial cancer treated with adjuvant chemoradiotherapy versus radiotherapy alone, with most clinically relevant benefit suggested for p53 abnormal cancers.”
Cathalijne C.B. Post, MD, of the Department of Radiation Oncology, Leiden University Medical Centre, Leiden, the Netherlands, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by the Dutch Cancer Society, Cancer Research UK, National Health and Medical Research Council Australia, Cancer Australia, Italian Medicines Agency, and Canadian Cancer Society Research Institute. For full disclosures of all study authors, visit thelancet.com.