Role of adjuvant therapy de-escalation for low-grade endometrioid endometrial cancer with adnexal only metastasis: call for research.

The 2023 International Federation of Gynecology and Obstetrics revision introduced stage IA3 to recognize a biologically favorable subset of low-grade endometrioid endometrial cancers characterized by superficial myometrial invasion, absence of substantial lymphovascular space invasion, and unilateral, intra-capsular ovarian involvement. This reclassification reflects an evolving understanding, shaped by pathology, molecular profiling, and outcomes research that many uterus-ovary endometrioid pairs are clonally related yet clinically indolent, challenging historical assumptions that all adnexal involvement warrants intensified adjuvant treatment. Emerging molecular data suggest that this pattern of disease reflects a form of restricted metastatic spread limited to the endometrium-ovary interface, where a uniquely compatible microenvironment allows localized implantation without widespread peritoneal dissemination. In this narrative review, we synthesize the current literature and prevailing schools of thought regarding the prognostic meaning of adnexal involvement, the distinction between synchronous double primaries and limited metastatic spread, and the implications of molecular classification for risk assessment. We summarize evidence indicating favorable survival in rigorously defined IA3 cohorts, while underscoring persistent uncertainties arising from retrospective study designs, variable pathologic thresholds, and incomplete molecular annotation. Rather than prescribing definitive management, this review frames IA3 as a testing ground for risk-adapted care that integrates meticulous pathology with molecular context, acknowledges areas of controversy, and identifies priorities for future research. Collectively, these perspectives aim to support thoughtful, individualized decision-making as the field converges on when "less may be more" for appropriately selected IA3 patients. Given the limited and retrospective nature of available data, definitive treatment recommendations cannot yet be made, reinforcing the need for prospective, molecularly stratified studies to inform future practice.