Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial

• Published in: The lancet oncology 2019-09, Vol.20 (9), p.1273-1285
• Main Authors: de Boer, Stephanie M, MD, Powell, Melanie E, MD, Mileshkin, Linda, MD, Katsaros, Dionyssios, Prof, Bessette, Paul, Prof, Haie-Meder, Christine, MD, Ottevanger, Petronella B, MD, Ledermann, Jonathan A, Prof, Khaw, Pearly, MD, D'Amico, Romerai, MD, Fyles, Anthony, Prof, Baron, Marie-Helene, MD, Jürgenliemk-Schulz, Ina M, PhD, Kitchener, Henry C, Prof, Nijman, Hans W, Prof, Wilson, Godfrey, MD, Brooks, Susan, MD, Gribaudo, Sergio, MD, Provencher, Diane, Prof, Hanzen, Chantal, MD, Kruitwagen, Roy F, Prof, Smit, Vincent T H B M, Prof, Singh, Naveena, MD, Do, Viet, MD, Lissoni, Andrea, MD, Nout, Remi A, MD, Feeney, Amanda, MSc, Verhoeven-Adema, Karen W, PhD, Putter, Hein, Prof, Creutzberg, Carien L, Prof
• Format: Article
• Language: English
• Subjects: Abdomen; Aged; Cancer; Cancer therapies; Carboplatin; Carboplatin - administration & dosage; Carboplatin - adverse effects; Chemoradiotherapy; Chemoradiotherapy, Adjuvant - adverse effects; Chemotherapy; Cisplatin; Cisplatin - administration & dosage; Cisplatin - adverse effects; Clinical trials; Decision making; Disease-Free Survival; Drug-Related Side Effects and Adverse Reactions; Endometrial cancer; Endometrial Neoplasms - drug therapy; Endometrial Neoplasms - pathology; Endometrial Neoplasms - radiotherapy; Endometrium; Female; Gynecology; Hematology, Oncology, and Palliative Medicine; Humans; Lymphatic system; Medical prognosis; Medical research; Metastases; Metastasis; Middle Aged; Myometrium; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - pathology; Neoplasm Recurrence, Local - radiotherapy; Neuropathy; Obstetrics; Oncology; Paclitaxel; Paclitaxel - administration & dosage; Paclitaxel - adverse effects; Pain; Patients; Radiation therapy; Radiotherapy - adverse effects; Risk Factors; Survival analysis; Treatment Outcome; Vagina; Womens health
• ISSN: 1470-2045; 1474-5488
• DOI: 10.1016/S1470-2045(19)30395-X

SummaryBackgroundThe PORTEC-3 trial investigated the benefit of combined adjuvant chemotherapy and radiotherapy versus pelvic radiotherapy alone for women with high-risk endometrial cancer. We updated the analysis to investigate patterns of recurrence and did a post-hoc survival analysis. MethodsIn the multicentre randomised phase 3 PORTEC-3 trial, women with high-risk endometrial cancer were eligible if they had International Federation of Gynaecology and Obstetrics (FIGO) 2009 stage I, endometrioid grade 3 cancer with deep myometrial invasion or lymphovascular space invasion, or both; stage II or III disease; or stage I–III disease with serous or clear cell histology; were aged 18 years and older; and had a WHO performance status of 0–2. Participants were randomly assigned (1:1) to receive radiotherapy alone (48·6 Gy in 1·8 Gy fractions given on 5 days per week) or chemoradiotherapy (two cycles of cisplatin 50 mg/m 2 given intravenously during radiotherapy, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m 2 given intravenously), by use of a biased coin minimisation procedure with stratification for participating centre, lymphadenectomy, stage, and histological type. The co-primary endpoints were overall survival and failure-free survival. Secondary endpoints of vaginal, pelvic, and distant recurrence were analysed according to the first site of recurrence. Survival endpoints were analysed by intention-to-treat, and adjusted for stratification factors. Competing risk methods were used for failure-free survival and recurrence. We did a post-hoc analysis to analyse patterns of recurrence with 1 additional year of follow-up. The study was closed on Dec 20, 2013; follow-up is ongoing. This study is registered with ISRCTN, number ISRCTN14387080, and ClinicalTrials.gov, number NCT00411138. FindingsBetween Nov 23, 2006, and Dec 20, 2013, 686 women were enrolled, of whom 660 were eligible and evaluable (330 in the chemoradiotherapy group, and 330 in the radiotherapy-alone group). At a median follow-up of 72·6 months (IQR 59·9–85·6), 5-year overall survival was 81·4% (95% CI 77·2–85·8) with chemoradiotherapy versus 76·1% (71·6–80·9) with radiotherapy alone (adjusted hazard ratio [HR] 0·70 [95% CI 0·51–0·97], p=0·034), and 5-year failure-free survival was 76·5% (95% CI 71·5–80·7) versus 69·1% (63·8–73·8; HR 0·70 [0·52–0·94], p=0·016). Distant metastases were the first site of recurrence in most patients with a relapse, occurring in 78 of 330 wome