Post-resection adrenocortical carcinoma with high recurrence-risk features — ENSAT stage...

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

ID	`RF-ACC-HIGH-RECURRENCE-RISK-BIOLOGY`
Type	Red flag
Status	reviewed 2026-07-11 \| pending_clinical_signoff
Diseases	`DIS-ADRENOCORTICAL-CARCINOMA`
Sources	`SRC-ADIUVO-TERZOLO-2023` `SRC-ENSAT-ACC-2018` `SRC-ESMO-ACC-2020`

Red Flag Origin

Definition	Post-resection adrenocortical carcinoma with high recurrence-risk features — ENSAT stage III, Ki-67 proliferation index >10%, or incomplete/uncertain (R1/RX) resection margin — defines the population for whom adjuvant mitotane is recommended. The randomized ADIUVO trial found no significant recurrence-free-survival benefit from adjuvant mitotane in the low/intermediate-risk group it enrolled (ENSAT stage I-III, R0 resection, Ki-67 <=10%).
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-ACC-1L

Trigger Logic

{
  "any_of": [
    {
      "finding": "acc_ensat_stage",
      "value": "III"
    },
    {
      "comparator": ">",
      "finding": "ki67_proliferation_index_pct",
      "threshold": 10
    },
    {
      "finding": "resection_margin_status",
      "value": "R1"
    },
    {
      "finding": "resection_margin_status",
      "value": "RX"
    }
  ],
  "type": "composite_clinical"
}

Notes

ADIUVO (Terzolo 2023, Lancet Diabetes Endocrinol) defined its low/intermediate-risk enrollment population as ENSAT stage I-III, R0 resection, Ki-67 <=10%, and found no significant recurrence-free- survival benefit from adjuvant mitotane in that population (5-yr RFS 79% mitotane vs 75% surveillance, HR 0.74, not significant). By extension, this RedFlag fires on the features that place a resected patient OUTSIDE the ADIUVO low/intermediate-risk definition: stage III, Ki-67 >10%, or incomplete/uncertain resection margin (R1/RX). This is this KB's first-pass operationalization of "high recurrence risk" for adjuvant mitotane and is STUB / pending clinical co-lead confirmation against the primary ENSAT/ESMO guideline text — those guidelines may specify additional or more granular risk criteria (e.g. tumor rupture, vascular invasion, mitotic count / Weiss-Helsinki score components) not yet encoded here. The finding keys used (acc_ensat_stage, ki67_proliferation_index_pct, resection_margin_status) are newly introduced in this authoring pass and not yet wired to any intake questionnaire — a mechanical/data-availability gap, not a clinical-content gap.

Used By

Algorithms

ALGO-ACC-1L - ALGO-ACC-1L

Drug

DRUG-MITOTANE - Mitotane

Indications

IND-ACC-1L-RESECTION-MITOTANE - IND-ACC-1L-RESECTION-MITOTANE

Regimens

REG-MITOTANE-ADJUVANT-ACC - Mitotane adjuvant monotherapy (ACC)

Sources

SRC-ADIUVO-TERZOLO-2023 - Adjuvant mitotane versus surveillance in low-grade, localised adrenocortical carcinoma (A...