Since the new guidelines for endometrial cancer risk classification have been published, many reviews have proposed a critical re-evaluation. In this review, we look back to how the molecular classification system was built and its evolution in time to highlight the major flaws, particularly the biases stemming from the inherent limitations of the cohorts involved in the discoveries. A significant drawback in some cohorts is the inclusion criteria, as well as the retrospective nature and the notably sparse numbers, especially in thePOLEmut(nonsynonymous mutation in EDM domain of POLE) risk groups, all of which impact the reliability of outcomes. Additionally, a disregard for variations in follow-up duration leads to a non-negligible bias, which raises a substantial concern in data interpretation and guideline applicability. Finally, according to the results that we obtained through a re-analysis of theconfirmation cohort, thep53abn(IHC positive for p53 protein) subgroup, which is predominant in non-endometrioid histology (73–80%), loses its predictivity power in the endometrioid cohort of patients. The exclusion of non-endometrioid subtypes from the cohort led to a complete overlap of three molecular subgroups (all exceptPOLEmut) for both overall and progression-free survival outcomes, suggesting the need for a more histotype-specific approach. In conclusion, this review challenges the current ESGO/ESTRO/ESP guidelines on endometrial cancer risk classification and highlights the limitations that must be addressed to better guide the clinical decision-making process.
自新版子宫内膜癌风险分类指南发布以来，诸多综述提出需对其进行批判性重估。本文通过回溯分子分型系统的构建历程及时序演变，重点剖析其核心缺陷，特别是受限于原始研究队列自身特性所产生的偏倚。部分队列存在显著缺陷：纳入标准存在局限、回顾性研究设计固有偏倚、关键亚组样本量严重不足（尤其POLEmut风险组），这些因素均影响研究结论的可靠性。此外，对随访时长差异的忽视导致不可忽略的偏倚，对数据解读与指南适用性构成实质性挑战。通过对验证队列的再分析发现，在非子宫内膜样组织学中占主导地位（73-80%）的p53abn亚组，在纯子宫内膜样癌队列中失去预后预测效力。剔除非子宫内膜样亚型后，除POLEmut组外其余三个分子亚组的总生存期与无进展生存期曲线完全重叠，提示需要建立更具组织学特异性的分型策略。本研究对现行ESGO/ESTRO/ESP子宫内膜癌风险分类指南提出质疑，并指出必须解决现有局限性以优化临床决策指导。
肿瘤(癌症)患者之家