Abstract
Background: ENDORISK is a Bayesian network that can assist in preoperative risk estimation of lymph node
metastasis (LNM) risk in endometrial cancer (EC) with consistent performance in external validations. To reflect
state of the art care, ENDORISK was optimized by integrating molecular classification and preoperative
assessment of myometrial invasion (MI).
Methods: Variables for POLE, MSI, and preoperative assessment of MI, either by expert transvaginal ultrasound or
pelvic magnetic resonance imaging (MRI), were added to develop ENDORISK-2. The p53 biomarker, part of the
molecular classification, was already included in ENDORISK. External validation of ENDORISK-2 for LNM prediction was performed in two independent cohorts from: Brno (CZ), (n = 581) and Tübingen (DE), (n = 247).
Findings: ENDORISK-2 yielded AUCs of 0⋅85 (95 % CI 0⋅80–0⋅90) (CZ) and 0⋅86 (95 % CI 0⋅77–0⋅96) (DE) for
predicting LNM. In patients with low-grade histology, 83 % (CZ) and 89 % (DE) were estimated having less than
10 % risk of LNM, with false negative rates (FNR) of 4⋅3 % (CZ) and 2⋅2 % (DE). The previously defined set of
minimally required variables, i.e.: preoperative tumor grade, three of the four immunohistochemical (IHC)
markers, and one clinical marker, could be interchanged with the new variables, with comparable validation
metrics, including AUC values of 0⋅79–0⋅87 for LNM prediction.
Interpretation. Incorporation of molecular data and preoperative MI improved the flexibility of ENDORISK with
comparable diagnostic accuracy for estimating LNM as when based on low-cost immunohistochemical biomarkers. In addition, the high diagnostic accuracy in patients with low-grade EC demonstrates how ENDORISK-2
could aid clinicians in identifying patients in whom surgical lymph node assessment may safely be omitted. These
results underline its power for clinical use in both high and low resource countries.
metastasis (LNM) risk in endometrial cancer (EC) with consistent performance in external validations. To reflect
state of the art care, ENDORISK was optimized by integrating molecular classification and preoperative
assessment of myometrial invasion (MI).
Methods: Variables for POLE, MSI, and preoperative assessment of MI, either by expert transvaginal ultrasound or
pelvic magnetic resonance imaging (MRI), were added to develop ENDORISK-2. The p53 biomarker, part of the
molecular classification, was already included in ENDORISK. External validation of ENDORISK-2 for LNM prediction was performed in two independent cohorts from: Brno (CZ), (n = 581) and Tübingen (DE), (n = 247).
Findings: ENDORISK-2 yielded AUCs of 0⋅85 (95 % CI 0⋅80–0⋅90) (CZ) and 0⋅86 (95 % CI 0⋅77–0⋅96) (DE) for
predicting LNM. In patients with low-grade histology, 83 % (CZ) and 89 % (DE) were estimated having less than
10 % risk of LNM, with false negative rates (FNR) of 4⋅3 % (CZ) and 2⋅2 % (DE). The previously defined set of
minimally required variables, i.e.: preoperative tumor grade, three of the four immunohistochemical (IHC)
markers, and one clinical marker, could be interchanged with the new variables, with comparable validation
metrics, including AUC values of 0⋅79–0⋅87 for LNM prediction.
Interpretation. Incorporation of molecular data and preoperative MI improved the flexibility of ENDORISK with
comparable diagnostic accuracy for estimating LNM as when based on low-cost immunohistochemical biomarkers. In addition, the high diagnostic accuracy in patients with low-grade EC demonstrates how ENDORISK-2
could aid clinicians in identifying patients in whom surgical lymph node assessment may safely be omitted. These
results underline its power for clinical use in both high and low resource countries.
| Original language | English |
|---|---|
| Article number | 116058 |
| Number of pages | 10 |
| Journal | European Journal of Cancer |
| Volume | 231 |
| Early online date | 1 Oct 2025 |
| DOIs | |
| Publication status | Published - 9 Dec 2025 |