Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): 10-year clinical outcomes and post-hoc analysis by molecular classification from a randomised phase 3 trial.

We present the preplanned long-term analysis of the randomised PORTEC-3 trial with a post-hoc analysis including molecular classification of the tumours.

我们展示了随机化PORTEC-3试验的预先计划的长期分析，包括对肿瘤进行分子分类的回顾性分析。

Methods

PORTEC-3 was an open-label, multicentre, randomised, international phase 3 trial. Women were eligible if they had high-risk endometrial cancer (either International Federation of Gynecology and Obstetrics 2009 stage I, grade 3, with deep myometrial invasion and/or lymphovascular space invasion; stage II-III; or stage I-III with serous or clear-cell histology), were aged 18 years or older, and had a WHO performance score of 0-2.

PORTEC-3 是一项开放标签、多中心、随机、国际 III 期试验。如果女性患有高风险子宫内膜癌（2009年国际妇产科联盟 I 期，3 级，伴有深肌层浸润和/或淋巴血管间隙侵犯；II-III 期；或 I-III 期伴有浆液性或透明细胞组织学类型），年龄在 18 岁或以上，并且 WHO 表现评分为 0-2 分，则符合资格。

Participants were randomly assigned (1:1) to receive pelvic radiotherapy (48·6 Gy in 1·8 Gy fractions) or chemoradiotherapy (radiotherapy combined with two cycles of cisplatin 50 mg/m2 intravenously in weeks one and four, followed by four cycles of carboplatin area-under-the-curve 5 and paclitaxel 175 mg/m2 intravenously at 3-week intervals).

参与者被随机分配（1:1）接受盆腔放射治疗（48.6 Gy，每次 1.8 Gy 分割）或同步放化疗（放射治疗结合顺铂 50 mg/m2 静脉注射，在第 1 周和第 4 周，随后是卡铂曲线下面积 5 和紫杉醇 175 mg/m2 静脉注射，间隔 3 周，共 4 个周期）。

Randomisation was done by use of biased-coin minimisation with stratification for participating centre, lymphadenectomy, stage, and histological type.

随机分组是通过使用有偏硬币最小化方法进行的，其中对参与中心、淋巴结清扫术、分期和组织学类型进行了分层。

We report the primary outcomes of overall survivaland recurrence-free survival at 10 years.

我们报告了10年总生存和无复发生存的主要结果。

We also report primary outcomes by molecular subgroup in a post-hoc analysis.

我们还在事后分析中按分子亚组报告了主要结果。

Survival was analysed in the intention-to-treatpopulation.

在意向治疗人群中分析了生存情况。

The study is registered with ClinicalTrials.gov (NCT00411138) and is now complete.

该研究已在ClinicalTrials.gov上注册（NCT00411138），目前研究已经完成。

Results

Between Nov 23, 2006, and Dec 20, 2013, 660 eligible and evaluable patients recruited at 103 centres in six clinical trial groups across seven countries were randomly assigned to chemoradiotherapy (n=330) or radiotherapy alone (n=330).

在2006年11月23日至2013年12月20日期间，来自七个不同国家的103个研究中心共招募了660名符合条件且可评估的患者，这些患者被随机分配接受同步放化疗（n=330）或单纯放疗（n=330）。

Median follow-up was 10·1 years (IQR 9·8-11·0).

中位随访时间为10.1年（四分位数间距9.8-11.0年）。

Estimated 10-year overall survivalwas 74·4% (95% CI 69·8-79·4) in the chemoradiotherapy group and 67·3% (62·3-72·7) in the radiotherapy group (adjusted hazard ratio[HR] 0·73 [95% CI 0·54-0·97], p=0·032), and 10-year recurrence-free survival was 72·8% (67·2-77·6) versus 67·4% (61·7-72·4; adjusted HR 0·74 [95% CI 0·56-0·98], p=0·034).

化疗联合放疗组的估计10年总生存率为74.4%（95%置信区间69.8-79.4），而单纯放疗组为67.3%（62.3-72.7）（调整后风险比[HR] 0.73 [95%置信区间0.54-0.97]，p=0.032），并且10年无复发生存率为72.8%（67.2-77.6）与67.4%（61.7-72.4；调整后HR 0.74 [95%置信区间0.56-0.98]，p=0.034）。

Molecular analysis was available for 411 (62%) patients (210 [64%] of 330 patients in the chemoradiotherapy group and 201 [61%] of 330 patients in the radiotherapy group), whose characteristics were similar to the overall trial population.

分子分析可用于411名（62%）患者（化疗放疗组210名（64%）和单纯放疗组201名（61%）），这些患者的特征与整个试验人群相似。

Post-hoc analysis by molecular class showed that, for women with p53 abnormal tumours, 10-year overall survivalwas 52·7% (95% CI 40·8-68·1) with chemoradiotherapy versus 36·6% (25·0 to 53·7) with radiotherapy alone (adjusted HR 0·52 [95% CI 0·30-0·91], p=0·021); 10-year recurrence-free survival was 52·6% (95% CI 38·3 to 65·0) versus 37·0% (95% CI 23·7 to 50·2; HR 0·42 [95% CI 0·24 to 0·74], p=0·0027).

按分子类别进行的事后分析显示，对于p53异常肿瘤的女性患者，化疗放疗组的10年总生存率为52.7%（95%置信区间40.8-68.1），而单纯放疗组为36.6%（25.0至53.7）（调整后风险比0.52 [95%置信区间0.30-0.91]，p=0.021）；10年无复发生存率为52.6%（95%置信区间38.3至65.0）与37.0%（95%置信区间23.7至50.2；风险比0.42 [95%置信区间0.24至0.74]，p=0.0027）。

MMRd and POLEmut cancers did not seem to benefit from chemoradiotherapy over radiotherapy alone, whereas the effects for NSMP cancers were modulated by oestrogen-receptor status.

MMRd和POLEmut癌症似乎没有从放化疗中获益超过单独放疗，而对于NSMP癌症的效果则受到雌激素受体状态的调节。

interpretation

10-year overall survivaland recurrence-free survival were improved for patients with high-risk endometrial cancer treated with adjuvant chemoradiotherapy versus radiotherapy alone, with most clinically relevant benefit suggested for p53 abnormal cancers.

对于高风险子宫内膜癌患者，辅助性放化疗与单独放疗相比，10年总生存和无复发生存得到改善，对于p53异常癌症的临床相关益处最为显著。

funding

Dutch Cancer Society, Cancer Research UK, National Health and Medical Research Council Australia, Cancer Australia, Italian Medicines Agency, and the Canadian Cancer Society Research Institute.

荷兰癌症学会、英国癌症研究、澳大利亚国家健康与医学研究委员会、澳大利亚癌症协会、意大利药品管理局以及加拿大癌症学会研究机构。