de Boer SM, et al. - In the PORTEC-3 trial, the benefit of adjuvant chemotherapy during and after radiotherapy (chemoradiotherapy) vs pelvic radiotherapy alone was investigated in women with high-risk endometrial cancer. No improvement was observed in 5-year overall survival as a result of administering adjuvant chemotherapy during and after radiotherapy, although it did increase failure-free survival. Individual counseling about this combined treatment was recommended for this patient population. Also, need for continued follow-up to evaluate long-term survival was also realized.

• An open-label, international, randomised, phase 3 trial (PORTEC-3) involving 103 centres in six clinical trials collaborating in the Gynaecological Cancer Intergroup was performed.
• Women who 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 were eligible.
• Random allocation of women (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) was done using a biased-coin minimisation procedure with stratification for participating centre, lymphadenectomy, stage of cancer, and histological type.
• Overall survival and failure-free survival were the co-primary endpoints.
• In addition, researchers used the Kaplan-Meier method, log-rank test, and Cox regression analysis for final analysis by intention to treat and adjusted for stratification factors.

• Between Nov 23, 2006, and Dec 20, 2013, a total of 686 women were enrolled.
• Of 660 eligible patients included in the final analysis, 330 were assigned to chemoradiotherapy and 330 were assigned to radiotherapy.
• Median follow-up was 60·2 months (IQR 48·1–73·1).
• According to data, 5-year overall survival was 81·8% (95% CI 77·5–86·2) with chemoradiotherapy vs 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) vs 68·6% (63·1–73·4; HR 0·71, 95% CI 0·53–0·95; p=0·022).
• A total of 198 (60%) of 330 who received chemoradiotherapy experienced grade 3 or worse adverse events during treatment, relative to 41 (12%) of 330 patients who received radiotherapy (p < 0·0001).
• Significant persistence of neuropathy (grade 2 or worse) was noted more often after chemoradiotherapy than after radiotherapy (20 [8%] women vs one [1%] at 3 years; p < 0·0001).
• Endometrial cancer caused most deaths; cause of death was uncertain in four patients (two in each group).
• Either disease progression or late treatment complications caused one death in the radiotherapy group; three deaths (two in the chemoradiotherapy group and one in the radiotherapy group) were due to either intercurrent disease or late treatment-related toxicity.