The Prediction of Recurrence in Low-Risk Endometrial Cancer: Is It Time for a Paradigm Shift in Adjuvant Therapy?

Five to 10% of patients with stage IA, grade 1 or 2, endometrioid adenocarcinoma subsequently develop locoregional or distant recurrence. These patients have significantly reduced 5-year survival rates and salvage therapy success rates as low as 40%. The aim of this review is to highlight knowledge gaps that could further refine the risk categories of endometrial carcinoma (EC) and guide future randomized trials of adjuvant therapy for low-risk EC. A systematic search of the literature on PubMed and Medline was conducted using the following search terms: endometrial cancer, endometrial adenocarcinoma, endometrioid adenocarcinoma, low grade, early stage, stage IA, low risk, locoregional recurrence, and relapse. Relevant primary studies were extracted and included in this review. Risk factors for recurrence of low-risk EC were epidemiological (age, body mass index, ethnicity), molecular (DNA MMR, MSI, TP53 mutation and P53 defect, CTNNB1 mutation, PTEN and POLE mutation, L1CAM expression), pathological (positive peritoneal cytology, lymphovascular invasion, tumor size), and others like Ki67-percentage, micro-RNA expression, and hormonal receptor expression. CTNNB1 mutation, L1CAM expression, lymphovascular invasion, and tumor size were identified as significant risk factors for recurrence in low-risk EC. There are subsets of low-risk EC patients at high risk of recurrence and should be suspected when having the following risk factors: positive molecular markers, large tumor size, and lymphovascular invasion. A novel scoring system and randomized controlled trials should be conducted to identify these patients who will benefit most from adjuvant therapy to avoid recurrence.