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Vienna, Austria

ESTRO 2023

Session Item

Sunday
May 14
11:40 - 12:40
Plenary Hall
Highlights of Proffered Papers - Best papers
Ludwig Van den Berghe, Belgium;
Marianne Aznar, United Kingdom
Proffered Papers
Interdisciplinary
11:50 - 12:00
Clinical Best Paper: Molecular classification of endometrial cancer is predictive of response to adjuvant radiotherapy
Nanda Horeweg, The Netherlands
OC-0508

Abstract

Molecular classification of endometrial cancer is predictive of response to adjuvant radiotherapy
Authors:

Nanda Horeweg1, Remi A. Nout2, Jan J. Jobsen3, Judy C.H.W. Lutgens4, Ina M. Jürgenliemk-Schulz5, Dorien M.A. Haverkort6, Jan Willem M. Mens7, Marianne A.A. de Jong8, Bastiaan G. Wortman1, Stephanie M. de Boer1, Hein Putter9, Ellen Stelloo10, Vincent T.H.B.M. Smit10, Tjalling Bosse10, Carien L. Creutzberg1

1Leiden University Medical Center, Radiation Oncology, Leiden, The Netherlands; 2Leiden University Medical Center (currently working at Erasmus MC Cancer Center), Radiation Oncology, Leiden (currently Rotterdam), The Netherlands; 3Medisch Spectrum Twente, Radiotherapy, Enschede, The Netherlands; 4Maastricht Radiation Oncology Clinic, Radiation Oncology, Maastricht, The Netherlands; 5University Medical Center Utrecht, Radiation Oncology, Utrecht, The Netherlands; 6Radiotherapiegroep, Radiotherapy, Arnhem, The Netherlands; 7Erasmus MC Cancer Institute, Radiation Oncology, Rotterdam, The Netherlands; 8Radiotherapeutic Institute Friesland, Radiotherapy, Leeuwarden, The Netherlands; 9Leiden University Medical Center, Biomedical data sciences, Leiden, The Netherlands; 10Leiden University Medical Center, Pathology, Leiden, The Netherlands

Show Affiliations
Purpose or Objective

The molecular classification of endometrial cancer (EC) has proven prognostic value and was found to be predictive for response to chemotherapy in the PORTEC-3 trial. The predictive value of the molecular classification for response to adjuvant radiotherapy has not yet been determined. Therefore, we investigated whether benefit of adjuvant radiotherapy differs across the four molecular classes.

Material and Methods

We evaluated the combined cohort of participants from the randomized PORTEC-1 (n=714) and -2 clinical trials (n=427). The PORTEC-1 and -2 trials respectively included women with intermediate and high-intermediate risk stage I endometrioid EC. In PORTEC-1 pelvic external beam radiotherapy (EBRT) was compared to no adjuvant treatment, and in PORTEC-2 vaginal brachytherapy (VBT) to EBRT. All cases that were molecularly profiled according to the WHO 2020 classification were included for analyses (n=484 of PORTEC-1 and n=396 of PORTEC-2). Locoregional recurrence-free survival (LRFS) was estimated using Kaplan-Meier’s methodology by adjuvant treatment with stratification for molecular class, and compared using log-rank tests.

Results

A total of 880 women with a median follow-up of 11.3 years were included (Table 1). Most women had stage I disease (96%) and tumors with an endometrioid histotype (98%). EC were classified as POLE-mutant (POLEmut, 8%) mismatch-repair deficient (MMRd, 28%), p53-abnormal (p53abn, 8%) and non-specific molecular profile (NSMP, 57%). In POLEmut EC, no recurrences were observed, even among those who had received no adjuvant therapy (Figure 1A). In MMRd EC, a small non-significant benefit of VBT and EBRT (5-year LRFS respectively 94% and 95%) over no adjuvant treatment was observed (89%, p=0.20, Figure 1B). In p53abn EC, EBRT (97%) but not VBT (64%) significantly improved LRFS compared to no adjuvant treatment (72%, p=0.042, figure 1C). In NSMP EC, both EBRT (98%) and VBT (96%) significantly improved LRFS (no adjuvant treatment 88%, p=0<0.0001, figure 1D).

Table 1. Overview of the included patients from the PORTEC-1 and -2 trials

Figure 1. Locoregional recurrence-free survival by adjuvant therapy across the four molecular groups of endometrial cancer


Conclusion

Benefit of adjuvant radiotherapy in stage I (high-)intermediate risk endometrioid EC differs between the four EC molecular classes. Omitting radiotherapy seems safe in early-stage POLEmut EC. Benefit of radiotherapy was not significant in MMRd EC, which may be due to the limited numbers. Women with p53abn EC have a substantially better prognosis when treated with EBRT, compared to brachytherapy and no adjuvant treatment. In women with NSMP EC, radiotherapy significantly reduces risk of recurrence. Since brachytherapy was as effective as EBRT, it is probably the adjuvant treatment of choice for NSMP EC.