Department of Radiation Oncology, Leiden University Medical Center Centrum, Leiden, Zuid-Holland, The Netherlands
Department of Radiation Oncology, Leiden University Medical Center Centrum, Leiden, Zuid-Holland, The Netherlands.
Int J Gynecol Cancer. 2021 Apr;31(4):594-604. doi: 10.1136/ijgc-2020-001822. Epub 2020 Oct 20.
Endometrial cancer is primarily treated with surgery. Adjuvant treatment strategies for endometrial cancer, such as external beam pelvic radiotherapy, vaginal brachytherapy, chemotherapy, and combined chemotherapy and radiotherapy, have been studied in several randomized trials. Adjuvant treatment is currently based on the presence of clinico-pathological risk factors. Low-risk disease is adequately managed with surgery alone. In high-intermediate risk endometrial cancer, adjuvant vaginal brachytherapy is recommended to maximize local control, with only mild side effects and without impact on quality of life. For high-risk endometrial cancer, recent large randomized trials support the use of pelvic radiotherapy, especially in stage I-II endometrial cancer with risk factors. For women with serous cancers and those with stage III disease, chemoradiation increased both recurrence-free and overall survival, while GOG-258 showed similar recurrence-free survival compared with six cycles of chemotherapy alone, but with better pelvic and para-aortic nodal control with combined chemotherapy and radiotherapy. Recent molecular studies, most notably the work from The Cancer Genome Atlas (TCGA) project, have shown that four endometrial cancer molecular classes can be distinguished; ultra-mutated, microsatellite instable hypermutated, copy-number-low, and copy-number-high. Subsequent studies, using surrogate markers to identify groups analogous to TCGA sub-classes, showed that all four endometrial cancer sub-types are found across all stages, histological types, and grades. Moreover, the molecular sub-groups have proved to have a stronger prognostic impact than histo-pathological tumor characteristics. This introduces an new era of molecular classification based diagnostics and treatment approaches. Integration of the molecular factors and new therapeutic targets will lead to molecular-integrated adjuvant treatment including targeted treatments, which are the rationale of new and ongoing trials. This review presents an overview of current adjuvant treatment strategies in endometrial cancer, highlights the development and evaluation of a molecular-integrated risk profile, and briefly discusses ongoing developments in targeted treatment.
子宫内膜癌主要通过手术治疗。几项随机试验研究了子宫内膜癌的辅助治疗策略，如外照射盆腔放疗、阴道近距离放疗、化疗以及化疗联合放疗。辅助治疗目前基于临床病理危险因素。低危疾病仅通过手术即可充分治疗。在中高危子宫内膜癌中，建议采用辅助阴道近距离放疗以最大限度地控制局部病变，同时副作用轻微，不影响生活质量。对于高危子宫内膜癌，最近的大型随机试验支持使用盆腔放疗，特别是对于有危险因素的 I 期-II 期子宫内膜癌。对于浆液性癌患者和 III 期疾病患者，放化疗增加了无复发生存率和总生存率，而 GOG-258 显示与单独化疗 6 个周期相比，无复发生存率相似，但联合化疗和放疗具有更好的盆腔和腹主动脉淋巴结控制。最近的分子研究，尤其是癌症基因组图谱（TCGA）项目的工作，表明可以区分四种子宫内膜癌分子类型；超高突变、微卫星不稳定高突变、拷贝数低和拷贝数高。随后的研究使用替代标志物来识别类似于 TCGA 亚类的组，表明所有四种子宫内膜癌亚型都存在于所有分期、组织学类型和分级中。此外，分子亚组被证明比组织病理学肿瘤特征具有更强的预后影响。这开创了基于分子分类的诊断和治疗方法的新时代。分子因素和新治疗靶点的整合将导致包括靶向治疗在内的分子综合辅助治疗，这是新的和正在进行的试验的基础。本文综述了子宫内膜癌目前的辅助治疗策略，强调了分子综合风险评估的发展和评估，并简要讨论了靶向治疗的最新进展。
