Stage I endometrial carcinoma with pathogenic POLE or POLD1 exonuclease-domain mutation (...

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`RF-POLE-POLD1-ENDOMETRIAL-LOW-RISK`
Type	Red flag
Status	reviewed 2026-04-29 \| pending_clinical_signoff
Diseases	`DIS-ENDOMETRIAL`
Sources	`SRC-ESGO-ENDOMETRIAL-2025` `SRC-ESMO-ENDOMETRIAL-2022` `SRC-NCCN-UTERINE-2025`

Red Flag Origin

Definition	Stage I endometrial carcinoma with pathogenic POLE or POLD1 exonuclease-domain mutation (POLE-EDM / POLD1-EDM hypermutator phenotype) — TCGA / TransPORTEC integrated classification predicts excellent recurrence-free survival; adjuvant chemotherapy/radiotherapy is NOT indicated. NCCN Uterine 2025 endorses observation only.
Clinical direction	de-escalate
Category	risk-score

Trigger Logic

{
  "all_of": [
    {
      "finding": "stage",
      "value": "I"
    },
    {
      "any_of": [
        {
          "finding": "BIO-POLE-HYPERMUTATOR",
          "value": "positive"
        },
        {
          "finding": "BIO-POLD1-HYPERMUTATOR",
          "value": "positive"
        }
      ]
    }
  ],
  "type": "biomarker_composite"
}

Notes

PORTEC-3 / TransPORTEC pooled analyses showed Stage I POLE-mutated endometrial carcinoma has near-100% recurrence-free survival without adjuvant therapy, even with high-grade morphology. POLD1-EDM is rarer but mechanistically equivalent and grouped with POLE in TCGA / ESGO-ESTRO integrated risk classification. de-escalate direction reflects avoidance of chemo/RT that would otherwise be considered for high-grade Stage I endometrial cancer. Routes care to IND-ENDOMETRIAL-STAGE-I-POLE-OBSERVATION. shifts_algorithm: empty because there is no Stage I endometrial algorithm yet — orchestrator should wire when ALGO-ENDOMETRIAL-STAGE-I lands. NCCN Uterine 2025 §UN-A and ESGO-ESTRO 2025 endometrial guideline both endorse observation for POLE-EDM Stage I.

Used By

Biomarker

BIO-POLD1-HYPERMUTATOR - POLD1 hypermutator phenotype (proofreading-domain mutation)
BIO-POLE-HYPERMUTATOR - POLE hypermutator phenotype (proofreading-domain mutation)