Espenel S, Pointreau Y, Genestie C, Durdux C, Haie-Meder C, Chargari C
Département de radiothérapie, Gustave-Roussy, 114, rue Édouard-Vaillant, 94805 Villejuif, France.
Département de radiothérapie, ILC-Institut interrégionaL de cancérologie, centre Jean-Bernard, 72000 Le Mans, France; Département de radiothérapie, centre régional universitaire de cancérologie Henry-S.-Kaplan, 37044 Tours, France.
Cancer Radiother. 2022 Oct;26(6-7):931-937. doi: 10.1016/j.canrad.2022.06.007. Epub 2022 Aug 26.
In Europe, endometrial cancer is the fourth most common cancer among women. The majority of patients are diagnosed at a localized stage. For these patients, the standard of care is based on an hysterectomy with salpingo oophorectomy±lymph node staging. Through the assessment of histopathologic features, risk groups are determined: low, intermediate, high-intermediate, and high risk. Adjuvant strategies are guided by these risk groups. While the prognosis of low-risk and high-risk is well known, that of intermediate and high-intermediate risk is more heterogeneous, and the therapeutic index of adjuvant treatments is more questionable. Several trials (PORTEC [Post Operative Radiation Therapy in Endometrial Carcinoma] I, GOG [Gynecologic Oncology Group] 99, ASTEC [A Study in the Treatment of Endometrial Cancer] EN.5, PORTEC II, Sorbe et al trial) have assessed observation, vaginal cuff brachytherapy and/or pelvic external beam radiotherapy in this population. Vaginal cuff brachytherapy reduces the local recurrence rate, and pelvic external beam radiotherapy the pelvic recurrence rate. However, no benefit in terms of overall survival or occurrence of distant metastases is highlighted. Compared to observation, brachytherapy and above all external beam radiotherapy are associated with an increased morbidity, and with a decreased quality of life. In order to improve the therapeutic ratio and to optimize medico-economic decisions, therapeutic de-escalation strategies, based on the molecular profiles, are emerging in clinical trials, and in the recommendations for the management of intermediate and high-intermediate risk endometrial cancers. The four main molecular profiles highlighted by the genomic analyzes of The Cancer Genome Atlas (TCGA) - POLE (polymerase epsilon) mutation, non-specific molecular profile, MMR (MisMatch repair) deficiency, and p53 mutation - but also the quantification of lymphovascular space invasion (absent, focal or substantial), and the assessment of L1CAM (L1 cell adhesion molecule) overexpression represent growing concerns. Thus, the use of molecular-integrated risk profile to determine the best adjuvant treatment represent a major way to personalize adjuvant treatment of endometrial cancers, with therapeutic de-escalation opportunity for around half of the high-intermediate risks. However, in the absence of prospective data, inclusion in clinical trials assessing molecular profile-based treatment remains the best therapeutic opportunity.
在欧洲，子宫内膜癌是女性中第四大常见癌症。大多数患者在疾病局限期被诊断出来。对于这些患者，标准治疗方案是行子宫切除术加双侧输卵管卵巢切除术±淋巴结分期。通过评估组织病理学特征，确定风险组：低风险、中风险、高中风险和高风险。辅助治疗策略依据这些风险组来制定。虽然低风险和高风险患者的预后情况较为明确，但中风险和高中风险患者的预后则更为异质，辅助治疗的治疗指数也更值得怀疑。多项试验（子宫内膜癌术后放射治疗[PORTEC]I、妇科肿瘤学组[GOG]99、子宫内膜癌治疗研究[ASTEC]EN.5、PORTEC II、索贝等人的试验）对该人群的观察、阴道残端近距离放射治疗和/或盆腔外照射放疗进行了评估。阴道残端近距离放射治疗可降低局部复发率，盆腔外照射放疗可降低盆腔复发率。然而，在总生存期或远处转移发生率方面未显示出益处。与观察相比，近距离放射治疗尤其是外照射放疗会增加发病率，并降低生活质量。为了提高治疗比率并优化医疗经济决策，基于分子特征的治疗降阶梯策略正在临床试验以及中风险和高中风险子宫内膜癌管理建议中出现。癌症基因组图谱（TCGA）的基因组分析突出显示的四种主要分子特征——POLE（聚合酶ε）突变、非特异性分子特征、错配修复（MMR）缺陷和p53突变——以及淋巴管间隙浸润的量化（无、局灶性或大量）和L1细胞粘附分子（L1CAM）过表达的评估都越来越受到关注。因此，使用分子综合风险特征来确定最佳辅助治疗是使子宫内膜癌辅助治疗个性化的主要方式，约一半的高中风险患者有治疗降阶梯的机会。然而，在缺乏前瞻性数据的情况下，纳入评估基于分子特征治疗的临床试验仍是最佳治疗选择。
