Assign classic Milan from a transparent lesion ledger, then separately reason about diagnosis, treatment response, OPTN policy, transplant eligibility and prognosis. Never use the binary label as an autonomous transplant decision.
{
"applicability": {
"use_for": "HCC_tumor_burden_selection_context_for_liver_transplantation",
"classification_unit": "one_patient_at_one_named_imaging_timepoint",
"required_inputs": [
"number_of_viable_HCC_observations",
"longest_viable_diameter_cm_for_each_observation",
"macrovascular_invasion",
"extrahepatic_spread",
"treatment_and_response_status",
"imaging_date_and_modality"
],
"clinical_context_required_but_not_part_of_binary_geometry": [
"cirrhosis_and_liver_function",
"portal_hypertension",
"performance_status",
"AFP_value_and_trajectory",
"resection_eligibility",
"transplant_contraindications",
"allocation_jurisdiction_and_center_protocol"
]
},
"categories": [
{
"outcome_code": "within-milan",
"all_required": [
"no_macrovascular_invasion",
"no_extrahepatic_spread"
],
"tumor_burden_any_of": [
"one_viable_HCC_with_longest_diameter_less_than_or_equal_to_5_cm",
"two_or_three_viable_HCCs_each_with_longest_diameter_less_than_or_equal_to_3_cm"
]
},
{
"outcome_code": "beyond-milan",
"any_of": [
"one_viable_HCC_greater_than_5_cm",
"two_or_three_viable_HCCs_with_any_lesion_greater_than_3_cm",
"four_or_more_viable_HCCs",
"macrovascular_invasion_present",
"extrahepatic_spread_present"
]
}
],
"assignment_algorithm": [
{
"step": 1,
"rule": "Confirm that observations are HCC by the applicable diagnostic pathway; do not count every indeterminate LI-RADS observation as HCC."
},
{
"step": 2,
"rule": "Create a lesion ledger with segment, viability, longest viable diameter, imaging date, modality and prior treatment."
},
{
"step": 3,
"rule": "If macrovascular invasion or extrahepatic spread is present, assign beyond Milan and state that decisive reason."
},
{
"step": 4,
"rule": "Otherwise apply the inclusive number-and-size branches exactly: one at most 5 cm, or two to three each at most 3 cm."
},
{
"step": 5,
"rule": "For post-treatment assessment, report both presenting/pre-treatment burden and current residual viable burden; never erase an originally beyond-Milan state after response."
}
],
"lesion_accounting_and_measurement": {
"untreated": "Count confirmed viable HCC observations and use the longest diameter of each lesion on technically adequate multiphasic CT or MRI.",
"after_locoregional_therapy": "Distinguish treated nonviable tissue from residual viable tumor and state the response framework. Current OPTN downstaging uses viable lesions after therapy, while the original presentation remains a separate eligibility fact.",
"multifocal_rule": "For two or three lesions, every lesion must be 3 cm or smaller; do not use the sum of diameters as the classic Milan test.",
"uncertainty_rule": "Preserve ranges and categorizability. A 3-cm or 5-cm boundary cannot be closed by undocumented rounding."
},
"decisive_boundaries": {
"single_exactly_5_cm": "Within Milan when there is no macrovascular invasion or extrahepatic spread.",
"single_greater_than_5_cm": "Beyond Milan by size.",
"three_each_exactly_3_cm": "Within Milan when every lesion is 3 cm or smaller and there is no macrovascular invasion or extrahepatic spread.",
"four_small_lesions": "Beyond classic Milan by number even if every lesion is smaller than 3 cm.",
"macrovascular_or_extrahepatic": "Beyond Milan regardless of otherwise qualifying intrahepatic number and size."
},
"OPTN_T2_boundary_US_policy": {
"no_equivalence_rule": "Within Milan is not synonymous with OPTN T2 or an automatically approved MELD/PELD exception.",
"current_T2_geometry": [
"one_OPTN_Class_5_lesion_2_to_5_cm_inclusive",
"two_or_three_OPTN_Class_5_lesions_each_1_to_3_cm_inclusive"
],
"AFP_gate": "AFP must be 1000 ng/mL or less for standard T2 exception eligibility; any prior AFP above 1000 invokes the separate post-treatment AFP rule.",
"key_counterexample": "A solitary confirmed HCC smaller than 2 cm can be within Milan but is not OPTN T2 for a standardized exception.",
"imaging_gate": "OPTN exception imaging must meet policy-specific dynamic contrast-enhanced CT or MRI and Class 5 documentation requirements; a generic Milan label is insufficient."
},
"OPTN_downstaging_boundary_US_policy": {
"initial_inclusion_any_of": [
"one_Class_5_lesion_greater_than_5_and_less_than_or_equal_to_8_cm",
"two_or_three_Class_5_lesions_with_at_least_one_greater_than_3_cm_each_less_than_or_equal_to_5_cm_and_total_diameter_less_than_or_equal_to_8_cm",
"four_or_five_Class_5_lesions_each_less_than_3_cm_and_total_diameter_less_than_or_equal_to_8_cm"
],
"success_requirement": "After locoregional therapy, viable lesions must meet OPTN T2 size requirements on dynamic contrast-enhanced CT or MRI.",
"outside_protocol": "A patient outside initial OPTN downstaging inclusion who later reaches T2 is not automatically eligible and requires National Liver Review Board consideration.",
"AFP_after_prior_above_1000": "After treatment AFP must fall below 500 ng/mL and remain below 500 for standardized eligibility; otherwise NLRB consideration is required.",
"no_crosswalk": "UNOS/OPTN downstaging inclusion, successful downstaging, classic Milan and T2 are four related but distinct states. Name the state and policy date."
},
"management_boundary": {
"within_milan": "Within Milan supports transplant consideration in an otherwise transplant-eligible patient; it does not itself place a patient on the waiting list, award exception points, choose transplant over resection or ablation, or override contraindications and organ availability.",
"transplant_context": "AASLD recommends liver transplantation for transplant-eligible early HCC with clinically significant portal hypertension and/or decompensated cirrhosis, after multidisciplinary assessment.",
"beyond_size_or_number_only": "Patients otherwise transplant eligible but beyond Milan, especially within UNOS downstaging inclusion, may be considered after successful downstaging to within Milan and an observation period of 3 to 6 months.",
"beyond_due_to_invasion_or_spread": "Report macrovascular invasion or extrahepatic spread explicitly and route to multidisciplinary staging and treatment; do not imply that geometric downstaging rules alone restore standard transplant eligibility.",
"policy_scope": "OPTN details apply to US deceased-donor allocation and exception policy. Living-donor practice, expanded criteria and non-US allocation require their own named protocol."
},
"risk_interpretation": {
"construct": "Milan is a selection boundary associated with favorable cohort outcomes, not an individualized recurrence or survival calculator.",
"determinants_outside_binary_label": [
"AFP_and_tumor_biology",
"response_to_locoregional_therapy",
"microvascular_invasion_not_visible_with_certainty",
"wait_time",
"liver_function",
"performance_status",
"donor_and_center_factors"
],
"historical_cohort_guard": "Do not present the original or later cohort survival percentages as this patient's probability.",
"beyond_guard": "Beyond Milan is heterogeneous and does not mean immediate futility, permanent transplant exclusion or one mandatory therapy."
},
"system_collision_boundary": {
"LI_RADS": "LI-RADS characterizes observations and treatment response; Milan aggregates confirmed HCC burden for transplant selection. An LR category is not a Milan result.",
"OPTN_T2": "OPTN T2 is a policy-defined exception stage with minimum lesion sizes and AFP rules; it is narrower than classic Milan in important cases.",
"BCLC": "BCLC integrates tumor stage, liver function and performance status to allocate treatment; Milan alone does not reconstruct BCLC or select therapy.",
"mRECIST_or_LR_TR": "Response frameworks define viable tumor after therapy; name the chosen framework and do not substitute the word viable without method.",
"expanded_criteria": "UCSF, up-to-seven, living-donor and center-specific criteria are separate named frameworks and must not silently redefine Milan."
},
"agent_output_contract": [
"State imaging date, modality, treatment status and the policy/jurisdiction date used.",
"Return a lesion-by-lesion ledger with segment, HCC diagnostic status, viability and longest viable diameter.",
"State macrovascular invasion and extrahepatic spread separately, including unknown when not assessed.",
"Return within or beyond classic Milan, the exact decisive branch and any boundary uncertainty.",
"For treated disease, return both presenting burden and current viable burden plus the response framework.",
"Separately evaluate OPTN T2, OPTN downstaging inclusion/success, AFP gates and NLRB need when US allocation is in scope.",
"Keep transplant eligibility, listing, exception points, treatment choice and individualized prognosis separate from the Milan label."
],
"missing_input_behavior": [
"If lesion count, largest viable diameter, macrovascular invasion or extrahepatic spread is unknown, return Milan_not_final and list the missing gate.",
"If a lesion straddles 3 or 5 cm, return a bounded within-versus-beyond result rather than rounding silently.",
"If post-treatment viability is not reported, do not count the entire treatment cavity as viable tumor or assume complete response.",
"If only within Milan is supplied, do not infer OPTN T2, AFP eligibility, listing status, BCLC stage or a treatment plan.",
"If only beyond Milan is supplied, request the exact reason because size/number excess, macrovascular invasion and extrahepatic spread have different policy and care implications."
],
"supporting_sources": [
{
"role": "classic_primary",
"citation": "Mazzaferro et al. N Engl J Med. 1996;334:693-699",
"doi": "10.1056/NEJM199603143341104"
},
{
"role": "current_clinical_guidance",
"citation": "Singal et al. Hepatology. 2023;78:1922-1965",
"doi": "10.1097/HEP.0000000000000466",
"pmcid": "PMC10663390"
},
{
"role": "current_US_allocation_policy",
"citation": "OPTN Policy 9.5.I, HCC MELD or PELD Score Exceptions, effective October 1, 2025",
"url": "https://www.hrsa.gov/sites/default/files/hrsa/optn/optn-policies.pdf"
}
],
"source_locator": "Mazzaferro et al. NEJM 1996, DOI 10.1056/NEJM199603143341104, Methods selection criteria; Singal et al. AASLD 2023, DOI 10.1097/HEP.0000000000000466, liver transplantation/downstaging sections and recommendations 33-36; OPTN Policies effective 2025-10-01, sections 9.5.I.i-vi, especially T2, downstaging and AFP requirements on pages 198-201."
}