TOPLINE:

In the PORTEC-3 trial, adjuvant chemoradiotherapy improved 10-year overall and recurrence-free survival in patients with high-risk endometrial cancer — particularly those with p53 abnormal tumors.

METHODOLOGY:

• About 15%-20% of patients with endometrial cancer presented with high-risk disease. The PORTEC-3 trial showed that for these patients, adding platinum-based chemotherapy to standard pelvic radiotherapy improves survival. This study reports on long-term outcomes, including an analysis by tumor molecular class.
• The PORTEC-3 trial was an open-label, multicenter, randomized phase 3 study involving 660 patients with high-risk endometrial cancer (stage I, grade 3 with deep myometrial invasion and/or lymphovascular space invasion; stages II-III; or stages I-III with serous or clear-cell histology). Patients were randomly assigned to either pelvic radiotherapy alone or chemoradiotherapy, which consisted of radiotherapy plus two cycles of cisplatin, followed by four cycles of carboplatin and paclitaxel.
• The primary outcomes of this long-term analysis were 10-year overall survival and recurrence-free survival. Post hoc molecular classification of tumors was available for 411 (62%) patients.

TAKEAWAY:

• Over a median follow-up of 10 years, 189 patients died, 77% from endometrial cancer. The estimated 10-year overall survival was 74.4% with chemoradiotherapy vs 67.3% with radiotherapy alone (adjusted hazard ratio [aHR], 0.73; P = .032).
• Overall, 10-year recurrence-free survival was 72.8% with chemoradiotherapy vs 67.4% with radiotherapy alone (aHR, 0.74; P = .034). Most recurrences occurred within the first 2.5 years of treatment and were predominantly distant metastases, with “excellent” local and regional nodal control in both treatment groups.
• In the post hoc analysis, about one quarter of patients had p53 abnormal tumors, and they showed the greatest benefit from chemoradiotherapy: 10-year overall survival was 52.7% with the combination vs 36.6% with radiotherapy alone (aHR, 0.52; P = .021). However, chemotherapy brought no added benefit to patients with either pathogenic POLE mutations (who had an overall survival rate above 96% with radiotherapy alone) or mismatch repair-deficient tumors.
• Findings were mixed for patients whose tumors had no specific molecular profile. For those with estrogen receptor-positive cancers, there was no overall survival advantage with chemoradiotherapy (81.8% vs 82.3% with radiotherapy alone). Patients with ER-negative cancers did seem to benefit from the addition of chemotherapy, but the authors stressed that the finding must be interpreted with caution due to the “very small” number of patients.

IN PRACTICE:

This long-term analysis supports previous findings of improved overall and recurrence-free survival with chemoradiotherapy among patients with high-risk endometrial cancer — but underscores a “crucial role” for molecular classification, the authors of the study wrote. “Given the clinically relevant therapeutic benefit with chemotherapy for stage I-III p53 abnormal cancers, adjuvant chemoradiotherapy is recommended,” they concluded. “For other molecular subgroups, treatment effect is less pronounced and might not outweigh the added toxicity.”

SOURCE:

The study, led by Cathalijne C.B. Post, MD, Leiden University Medical Centre, Leiden, Netherlands, was published online in The Lancet Oncology.

LIMITATIONS:

Predefined threshold of overall survival events was not reached. Molecular subgroup analyses were underpowered due to small sample size. Additionally, the definition of high-risk endometrial cancer has evolved over time, though the subgroups with the largest chemotherapy benefit are still classified as high risk.

DISCLOSURES:

The study was supported by the Dutch Cancer Society, Cancer Research UK, National Health and Medical Research Council of Australia, Cancer Australia, Italian Medicines Agency, and the Canadian Cancer Society Research Institute. Several authors reported receiving grants or consulting fees and having other ties with various sources. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.