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Jump to Key Points The management of endometrial cancer is progressing. But after surgery, one question remains paramount: Should treatment be administered, and if so, how? Until now, the decision was based on tumor, node and metastasis staging, grade, and histologic subtype. This trio is now proving insufficient on its own and is being supplemented by an algorithm developed by UCLouvain, one of the oldest universities in Europe, located in Belgium.
The Cancer Genome Atlas project has shown that in endometrial cancer — particularly in high-grade endometrioid carcinomas — the molecular profile is a better predictor of prognosis than histology alone. The proactive molecular endometrial risk classifier has made this approach accessible in routine clinical practice at a lower cost. As a result, the FIGO 2023 staging system now includes four molecular groups — POLEmut, mismatch repair deficiency (MMRd), abnormal p53, and no specific molecular profile — in addition to the traditional histologic criteria. Today, every patient should be able to benefit from a molecular tumor profile and a lymph node assessment. These two parameters are now the primary determinants of the risk for recurrence.
A Practical Algorithm, Published at Saint-Luc
It is in this context that Jean-François Baurain et al, of the Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium, proposed a tool to guide adjuvant treatment for early-stage disease, which includes four risk groups and four strategies:
- Low risk for recurrence (< 8%): stages IA1/IC, POLEmut stages I–II, low-grade MMRd without invasion. No adjuvant treatment
- Intermediate risk (8%-15%): Vaginal brachytherapy is sufficient — as shown by the PORTEC-2 trial — and offers a better quality of life than external beam radiation therapy. For women under 60, treatment-free observation remains a validated option.
- Intermediate-high risk (15%-25%): The combination of chemotherapy and radiation therapy is indicated, except in patients with an MMRd tumor, for whom PORTEC-3 showed no additional benefit from chemotherapy. New finding: The ENGOT-en11 trial tested pembrolizumab in high-risk MMRd patients and observed a relapse rate of 6% in the experimental arm (hazard ratio, 0.31).
- High risk (> 25%): routine chemoradiotherapy. PORTEC-3 and GOG-258 agree: radiation therapy prevents pelvic relapses, while chemotherapy slows distant metastases. Despite this strategy, nearly one in two patients will relapse. Hence the value of PARP inhibitors (RAINBO Red trial) in patients with p53-abnormal tumors, which share molecular characteristics with ovarian cancer.
What Needs to Change in Practice
Routine lymphadenectomy is losing ground. Sentinel lymph node biopsy is gaining traction, but its role remains debated outside the low-risk category; the ALICE, ENDO-3, and SELECT trials should help settle the matter. In the meantime, the absence of lymph node evaluation should be coded as NX, with no impact on staging.
- Molecular profile now key prognostic factor; FIGO 2023 adds 4 molecular groups.
- Early-stage adjuvant therapy guided by recurrence risk + nodal assessment.
- Low risk (<8%): no adjuvant therapy; POLEmut I-II, low-grade MMRd without invasion.
- Intermediate-high risk MMRd: chemoRT may add no benefit; pembrolizumab trial relapse 6%.
- Sentinel node biopsy rising; routine lymphadenectomy declining, NX if nodes not assessed.
This decision algorithm is not a new national recommendation: It is an operational translation of the 2025 ESGO/ESTRO/ESP recommendations, designed for routine multidisciplinary team meetings. It helps structure a decision that has become difficult to remember without visual aids. This tool was designed to integrate directly into local care pathways.
This story was translated from MediQuality, part of the Medscape Professional Network.
