Long-Term Toxicity and Health-Related Quality of Life After Adjuvant Chemoradiation Therapy or Radiation Therapy Alone for High-Risk Endometrial Cancer in the Randomized PORTEC-3 Trial

C.C.B. Post*, S.M. de Boer, M.E. Powell, L. Mileshkin, D. Katsaros, P. Bessette, C. Haie-Meder, N.P.B. Ottevanger, J.A. Ledermann, P. Khaw, R. D'Amico, A. Fyles, M.H. Baron, H.C. Kitchener, H.W. Nijman, L.C.H.W. Lutgens, S. Brooks, I.M. Jurgenliemk-Schulz, A. Feeney, G. GossR. Fossati, P. Ghatage, A. Leary, V. Do, A.A. Lissoni, M. McCormack, R.A. Nout, K.W. Verhoeven-Adema, V.T.H.B.M. Smit, H. Putter, C.L. Creutzberg

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Web of Science)


Purpose: The survival results of the PORTEC-3 trial showed a significant improvement in both overall and failure-free survival with chemoradiation therapy versus pelvic radiation therapy alone. The present analysis was performed to compare long-term adverse events (AE) and health-related quality of life (HRQOL).

Methods and Materials: In the study, 660 women with high-risk endometrial cancer were randomly assigned to receive chemoradiation therapy (2 concurrent cycles of cisplatin followed by 4 cycles of carboplatin/paclitaxel) or radiation therapy alone. Toxicity was graded using Common Terminology Criteria for Adverse Events, version 3.0. HRQOL was measured using EORTC QLQ-C30 and CX24/OV28 subscales and compared with normative data. An as-treated analysis was performed.

Results: Median follow-up was 74.6 months; 574 (87%) patients were evaluable for HRQOL. At 5 years, grade >= 2 AE were scored for 78 (38%) patients who had received chemoradiation therapy versus 46 (24%) who had received radiation therapy alone (P = .008). Grade 3 AE did not differ significantly between the groups (8% vs 5%, P = .18) at 5 years, and only one new late grade 4 toxicity had been reported. At 3 and 5 years, sensory neuropathy toxicity grade >= 2 persisted after chemoradiation therapy in 6% (vs 0% after radiation therapy, P < .001) and more patients reported significant tingling or numbness at HRQOL (27% vs 8%, P < .001 at 3 years; 24% vs 9%, P = .002 at 5 years). Up to 3 years, more patients who had chemoradiation therapy reported limb weakness (21% vs 5%, P < .001) and lower physical (79 vs 87, P < .001) and role functioning (78 vs 88, P < .001) scores. Both treatment groups reported similar long-term global health/quality of life scores, which were better than those of the normative population.

Conclusions: This study shows a long-lasting, clinically relevant, negative impact of chemoradiation therapy on toxicity and HRQOL, most importantly persistent peripheral sensory neuropathy. Physical and role functioning impairments were seen until 3 years. These long-term data are essential for patient information and shared decision-making regarding adjuvant chemotherapy for high-risk endometrial cancer. (C) 2020 The Author(s). Published by Elsevier Inc.

Original languageEnglish
Pages (from-to)975-986
Number of pages12
JournalInternational Journal of Radiation Oncology Biology Physics
Issue number4
Publication statusPublished - 15 Mar 2021

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