Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial

Abstract

SummaryBackgroundAlthough women with endometrial cancer generally have a favourable prognosis, those with high-risk disease features are at increased risk of recurrence. The PORTEC-3 trial was initiated to investigate the benefit of adjuvant chemotherapy during and after radiotherapy (chemoradiotherapy) versus pelvic radiotherapy alone for women with high-risk endometrial cancer.MethodsPORTEC-3 was an open-label, international, randomised, phase 3 trial involving 103 centres in six clinical trials collaborating in the Gynaecological Cancer Intergroup. Eligible women had high-risk endometrial cancer with FIGO 2009 stage I, endometrioid-type grade 3 with deep myometrial invasion or lymph-vascular space invasion (or both), endometrioid-type stage II or III, or stage I to III with serous or clear cell histology. Women were randomly assigned (1:1) to receive radiotherapy alone (48·6 Gy in 1·8 Gy fractions given on 5 days per week) or radiotherapy and chemotherapy (consisting of two cycles of cisplatin 50 mg/m2 given during radiotherapy, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m2) using a biased-coin minimisation procedure with stratification for participating centre, lymphadenectomy, stage of cancer, and histological type. The co-primary endpoints were overall survival and failure-free survival. We used the Kaplan-Meier method, log-rank test, and Cox regression analysis for final analysis by intention to treat and adjusted for stratification factors. The study was closed on Dec 20, 2013, after achieving complete accrual; follow-up is ongoing. PORTEC-3 is registered with ISRCTN, number ISRCTN14387080, and ClinicalTrials.gov, number NCT00411138.Results686 women were enrolled between Nov 23, 2006, and Dec 20, 2013. 660 eligible patients were included in the final analysis, of whom 330 were assigned to chemoradiotherapy and 330 were assigned to radiotherapy. Median follow-up was 60·2 months (IQR 48·1–73·1). 5-year overall survival was 81·8% (95% CI 77·5–86·2) with chemoradiotherapy versus 76·7% (72·1–81·6) with radiotherapy (adjusted hazard ratio [HR] 0·76, 95% CI 0·54–1·06; p=0·11); 5-year failure-free survival was 75·5% (95% CI 70·3–79·9) versus 68·6% (63·1–73·4; HR 0·71, 95% CI 0·53–0·95; p=0·022). Grade 3 or worse adverse events during treatment occurred in 198 (60%) of 330 who received chemoradiotherapy versus 41 (12%) of 330 patients who received radiotherapy (p<0·0001). Neuropathy (grade 2 or worse) persisted significantly more often after chemoradiotherapy than after radiotherapy (20 [8%] women vs one [1%] at 3 years; p<0·0001). Most deaths were due to endometrial cancer; in four patients (two in each group), the cause of death was uncertain. One death in the radiotherapy group was due to either disease progression or late treatment complications; three deaths (two in the chemoradiotherapy group and one in the radiotherapy group) were due to either intercurrent disease or late treatment-related toxicity.InterpretationAdjuvant chemotherapy given during and after radiotherapy for high-risk ...

Muscle radiodensity loss during cancer therapy is predictive for poor survival in advanced endometrial cancer

“…The optimal adjuvant treatment for stage III EC has been unclear. The GOG 258 and PORTEC‐3 trials found that adjuvant CRT did not improve OS, although radiotherapy significantly reduced vaginal and pelvic recurrences . In this study, the 5 year OS and PFS were similar to the final results of the PORTEC‐3 trial.…”

Lymphadenectomy and Adjuvant Therapy Improve Survival with Uterine Carcinosarcoma: A Large Retrospective Cohort Study

“…Apparently, cases with positive nodes are at an increased risk of recurrence despite LND. This finding corresponds to the recent findings of the PORTEC-3 trial, which investigated the benefit of adjuvant treatment for other histologic types of high-risk endometrial cancer [16]. A clinical consequence could be to omit adjuvant treatment when nodes are negative.…”

Cancer of the corpus uteri

“…In the PORTEC‐3 trial, patients with high‐risk Stage I–II (32% grade 3 and 29% serous or clear cell cancer) or with Stage III (45%) endometrial cancer were randomly allocated to pelvic EBRT alone or EBRT with two concurrent cycles of cisplatin in weeks 1 and 4 of EBRT, followed by four cycles of carboplatin and paclitaxel. At a median follow‐up of 60.2 months, there was no significant difference in overall survival between the arms, but a significant difference in failure‐free survival, with women in the combined chemoradiotherapy arm having 7% higher failure‐free survival (76% vs 69%; P =0.022) . Women with Stage III disease had the highest absolute benefit of chemoradiotherapy, with 5‐year failure‐free survival of 69% versus 58% for radiotherapy alone ( P =0.03).…”