Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Gynecol Oncol. 2024 Jun;185:121-127. doi: 10.1016/j.ygyno.2024.02.020. Epub 2024 Feb 24.
The traditional histological classification system for endometrial carcinoma falls short in addressing the disease's molecular heterogeneity, prompting the need for alternative stratification methods. Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) has emerged as a clinically efficient tool to categorize endometrial cancers according to mismatch repair deficiency, POLE exonuclease domain mutations, and p53 expression. However, the application of this classification to fertility-sparing treatments remains unexplored, and current guidelines lack specificity in how it should be used. In this review, we summarize the available literature and establish the framework for future investigations focused on molecular profiling-based risk assessment of endometrial cancer, with the goal of utilizing precision medicine to optimally counsel patients seeking fertility-sparing treatment. While the available evidence is limited and of low quality, it does provide insights and frames future perspectives for managing fertility-sparing approaches on the basis of molecular subtypes. Evidence suggests that mismatch repair-deficient tumors are likely to recur despite progestin therapy, emphasizing the need for alternative treatments, with targeted therapies being a new landscape that still needs to be explored. Tumors with POLE mutations exhibit a favorable prognosis, but the safety of hysteroscopic resection alone requires further investigation. p53 abnormal tumors have an unfavorable prognosis, raising questions about their suitability for fertility-sparing treatment. Lastly, the no specific molecular profile (or p53 wild-type) tumors, while having a relatively good prognosis, are heterogeneous and require more precise biomarkers to effectively guide therapy for those with poorer prognoses. Addressing these research gaps will lead to more precise guidelines to ensure optimal selection for fertility-sparing treatment.
传统的子宫内膜癌组织学分类系统在解决疾病的分子异质性方面存在不足,因此需要替代的分层方法。Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) 已成为一种临床有效的工具,可根据错配修复缺陷、POLE 外切酶结构域突变和 p53 表达对子宫内膜癌进行分类。然而,这种分类方法在保留生育能力的治疗中的应用尚未得到探索,目前的指南缺乏关于如何使用该方法的具体说明。在这篇综述中,我们总结了现有文献,并为基于分子谱分析的子宫内膜癌风险评估的未来研究建立了框架,旨在利用精准医学为寻求保留生育能力治疗的患者提供最佳咨询。尽管现有证据有限且质量较低,但它确实为基于分子亚型的保留生育能力方法的管理提供了见解和未来展望。证据表明,尽管孕激素治疗,但错配修复缺陷肿瘤仍有可能复发,因此需要替代治疗方法,靶向治疗是一个需要探索的新领域。POLE 突变的肿瘤预后良好,但单纯宫腔镜切除术的安全性需要进一步研究。p53 异常肿瘤预后不良,这引发了关于其是否适合保留生育能力治疗的问题。最后,没有特定分子谱(或 p53 野生型)的肿瘤虽然预后相对较好,但具有异质性,需要更精确的生物标志物来有效指导预后较差患者的治疗。解决这些研究空白将有助于制定更精确的指南,以确保为保留生育能力的治疗进行最佳选择。