Molecular Classification and Response to Radiotherapy in Early-Stage Endometrioid Endometrial Cancer

Get Permission

In a Dutch analysis reported in the Journal of Clinical Oncology, Horeweg et al found that molecular classification predicted response to radiotherapy in patients with early-stage endometrioid endometrial cancer.

As stated by the investigators, “The molecular classification of endometrial cancer has proven to have prognostic value and is predictive of response to adjuvant chemotherapy. Here, we investigate its predictive value for response to external-beam radiotherapy (EBRT) and vaginal brachytherapy (VBT) in early-stage endometrioid endometrial cancer.

Study Details

The study involved data from patients in the PORTEC-1 trial, which evaluated pelvic EBRT with no adjuvant therapy in individuals with early-stage intermediate-risk endometrial cancer, and the PORTEC-2 trial, which compared VBT with EBRT in patients with early-stage high-intermediate–risk endometrial cancer.

Key Findings

A total of 880 patients with molecularly classified endometrial cancer—484 from PORTEC-1 and 396 from PORTEC-2—were included in the analysis; overall, 97.2% had FIGO-2009 stage I endometrioid endometrial cancer.

No locoregional recurrences were observed among 66 patients with pathogenic mutation of DNA polymerase-e (POLEmut) endometrial cancer at 5 years.

Among 247 patients with mismatch repair–deficient (MMRd) endometrial cancer, 5-year locoregional recurrence-free survival was 94.2% with EBRT, 94.2% with VBT, and 90.3% with no adjuvant therapy (overall P = .74).

Among 70 patients with a p53 abnormality, 5-year locoregional recurrence-free survival was 96.9% with EBRT, 64.3% with VBT, and 72.2% with no adjuvant therapy (overall P = .048).

Among 497 patients with no specific molecular profile, 5-year locoregional recurrence-free survival was 98.3% with EBRT, 96.2% with VBT, and 87.7% with no adjuvant therapy (overall P < .0001).

The investigators concluded, “The molecular classification of endometrial cancer predicts response to radiotherapy in stage I endometrioid endometrial cancer and may guide adjuvant treatment decisions. Omitting radiotherapy seems to be safe in POLEmut endometrial cancer. The benefit of radiotherapy seems to be limited in MMRd endometrial cancer. EBRT yields a significantly better locoregional recurrence-free survival than VBT or no adjuvant therapy in [patients with endometrial cancer and a p53 abnormality]. VBT is the treatment of choice for [patients with endometrial cancer and no specific molecular profile] as it is as effective as EBRT and significantly better than no adjuvant therapy for locoregional tumor control.”

Nanda Horeweg, MD, PhD, of the Department of Radiation Oncology, Leiden University Medical Center, the Netherlands, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by grants from the Dutch Cancer Society. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.