Department of Radiation Oncology, Leiden University Medical Center, Leiden, the Netherlands.
Department of Radiotherapy, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
J Clin Oncol. 2023 Sep 20;41(27):4369-4380. doi: 10.1200/JCO.23.00062. Epub 2023 Jul 24.
The molecular classification of endometrial cancer (EC) has proven to have prognostic value and is predictive of response to adjuvant chemotherapy. Here, we investigate its predictive value for response to external beam radiotherapy (EBRT) and vaginal brachytherapy (VBT) in early-stage endometrioid EC (EEC).
Data of the randomized PORTEC-1 trial (n = 714) comparing pelvic EBRT with no adjuvant therapy in early-stage intermediate-risk EC and the PORTEC-2 trial (n = 427) comparing VBT with EBRT in early-stage high-intermediate-risk EC were used. Locoregional (including vaginal and pelvic) recurrence-free survival was compared between treatment groups across the four molecular classes using Kaplan-Meier's methodology and log-rank tests.
A total of 880 molecularly classified ECs, 484 from PORTEC-1 and 396 from PORTEC-2, were included. The majority were FIGO-2009 stage I EEC (97.2%). The median follow-up was 11.3 years. No locoregional recurrences were observed in EC with a pathogenic mutation of DNA polymerase-ε (mut EC). In mismatch repair-deficient (MMRd) EC, locoregional recurrence-free survival was similar after EBRT (94.2%), VBT (94.2%), and no adjuvant therapy (90.3%; = .74). In EC with a p53 abnormality (p53abn EC), EBRT (96.9%) had a substantial benefit over VBT (64.3%) and no adjuvant therapy (72.2%; = .048). In EC with no specific molecular profile (NSMP EC), both EBRT (98.3%) and VBT (96.2%) yielded better locoregional control than no adjuvant therapy (87.7%; < .0001).
The molecular classification of EC predicts response to radiotherapy in stage I EEC and may guide adjuvant treatment decisions. Omitting radiotherapy seems to be safe in mut EC. The benefit of radiotherapy seems to be limited in MMRd EC. EBRT yields a significantly better locoregional recurrence-free survival than VBT or no adjuvant therapy in p53abn EC. VBT is the treatment of choice for NSMP EC as it is as effective as EBRT and significantly better than no adjuvant therapy for locoregional tumor control.
子宫内膜癌（EC）的分子分类已被证明具有预后价值，并可预测辅助化疗的反应。在这里，我们研究其对早期子宫内膜样 EC（EEC）的外照射放疗（EBRT）和阴道近距离放疗（VBT）的反应的预测价值。
我们使用了比较盆腔 EBRT 与早期中危 EC 无辅助治疗的 PORTEC-1 试验（n = 714）和比较早期高-中危 EC 中 VBT 与 EBRT 的 PORTEC-2 试验（n = 427）的数据。使用 Kaplan-Meier 方法和对数秩检验比较四个分子类别中治疗组之间的局部区域（包括阴道和盆腔）无复发生存率。
共纳入 880 例分子分类的 EC 患者，其中 484 例来自 PORTEC-1，396 例来自 PORTEC-2。大多数为 FIGO-2009 期 I EEC（97.2%）。中位随访时间为 11.3 年。在具有致病性 DNA 聚合酶 ε 突变的 EC（mut EC）中未观察到局部区域复发。在错配修复缺陷（MMRd）EC 中，EBRT（94.2%）、VBT（94.2%）和无辅助治疗（90.3%；=.74）后的局部区域无复发生存率相似。在具有 p53 异常（p53abn EC）的 EC 中，EBRT（96.9%）明显优于 VBT（64.3%）和无辅助治疗（72.2%；=.048）。在无特定分子谱（NSMP EC）的 EC 中，EBRT（98.3%）和 VBT（96.2%）的局部区域控制效果均优于无辅助治疗（87.7%；<.0001）。
EC 的分子分类可预测 I 期 EEC 对放疗的反应，可能指导辅助治疗决策。在 mut EC 中，省略放疗似乎是安全的。在 MMRd EC 中，放疗的益处似乎有限。在 p53abn EC 中，EBRT 比 VBT 或无辅助治疗有更好的局部区域无复发生存率。对于 NSMP EC，VBT 是首选治疗方法，因为它与 EBRT 一样有效，并且在局部区域肿瘤控制方面明显优于无辅助治疗。
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