Table 1.

Application Rules for Staging and Allocation

1	The system applies only to early and intermediate stage HCC presenting in compensated cirrhosis/chronic liver diseases (stages BCLC‐A and BCLC‐B). Exclusion criteria are vascular invasion, extrahepatic spread and comorbidities. HCC arising in decompensated (Child‐Pugh class C) cirrhosis is determined by laboratory MELD score and receives priority accordingly.
2	In principle, any HCC arising in compensated cirrhosis is considered as TT once inclusion/exclusion criteria are satisfied. Morphology criteria (i.e., tumor size and number) used for transplantation eligibility should be defined a priori at a regional level depending on the dynamics of the waiting list, proportion of enlisted HCC versus non‐HCC patients, harm to patients who remain on the waiting list, donor availability, etc., and should not be modified at any time during patient follow‐up (i.e., up to LT, dropout, or death). Morphology criteria reported objectively should be integrated with pathologic/biologic information (e.g., tumor biopsy, AFP levels) when available, and all information should be discussed before the tumor transplantation board (see points 3 and 4 below). AFP cutoff levels able to exclude transplantation eligibility even in presence of permissive tumor morphology conditions should be defined a priori as well, as that limit currently ranges from 200 to 1000 ng/mL21, 32, 39, 41, 42, 43 or according to steady increase over time.32
3	All TT should be treated with the single/combined best available treatment according to internal protocols and/or accepted guidelines and should be reconsidered for class assignment at the end of each treatment course. Accordingly, any decision regarding treatment of a TT should take into account the transplantation implications before and after therapy courses.
4	Reproducible criteria for imaging, diagnosis, classification, and reporting in HCC before and after treatment should follow common accepted standards determined a priori 30, 31 and should also consider the contribution of tumor growth rate49 and patterns of residual disease determination.50 Digital imaging should be accessible for internal or external audits.
5	If TT are not treatable due to technical or medical reasons not captured by MELD score (i.e., ascites), the patient should be classified as having untreatable HCC (TTUT) and prioritized accordingly.
6	Point assignment and priority class should be managed dynamically, because disease status may change over time depending on biology and therapy. Stepwise assessments should be undertaken at a minimum of four possible time points: a) at tumor presentation (baseline assessment), if TT meets points n.1 and 2 above; b) in stabilized tumor conditions (i.e., stable disease for a sufficient period of time [at least 3 months])7, 17, 21; c) in case of tumor progression during treatment;a d) at the end of each treatment course.
7	Patients included in downstaging protocols should be considered as TT0NT (intermediate priority) in case of complete response at the end of treatment—due to the initial tumor stage exceeding conventional criteria—or as TTDR (high priority) in case of suboptimal downsizing and/or residual tumor remaining reasonably stable over time in patients still meeting transplantation criteria. For patients included in “extended limits for downstaging” protocols, LT listing could be considered only after complete response and if part of prospective investigations.
8	Because changes that occur in serum AFP levels while patients are on the waiting list correspond closely to changes in posttransplantation mortality,51 AFP trends should parallel radiologic tumor response (or progression) of a transplantable tumor during treatment and/or follow‐up. In principle, patients who have a major drop in AFP level after treatment should be considered at a more significant level than those who do not. In patients included in downstaging protocols (see point 7 above), differential drop and absolute APF level could help in discriminating various levels of response—and priority‐among different patients with similar radiology‐assessed posttreatment response.
9	Recurrent HCC should be approached similarly to naïve HCC, with identical treatment aims and general requirements as listed above in points 1‐5. Recurrent HCC may be classified as TTFR or TTDR according to the time of recurrence, whether this is ≤2 years (i.e., early recurrence) or >2 years (i.e., late recurrence) from the original curative treatment. This yields different priorities because of the higher risk of dropout in early recurring tumors. • Early recurrences should be listed only if the tumor meets transplantable criteria both at the time of original treatment and after cumulative staging, which is calculated at the time of transplantation consideration. The cumulative stage of an early recurring HCC considers one tumor entity as the sum of the first presenting HCC + recurrent tumor. • Late recurrences should be listed if meeting transplantation criteria at the time of transplantation consideration, as they could be rated as TTFR regardless of the stage of the first‐presenting HCC curatively removed >2 years ago.
10	Exceptions to the general frame of stage progression and priorities are allowed with approval from a regional reviewer board. In the current scenario, exceptions may be related to: experimental de principe transplantation strategies applied to resected tumors (TT0c); observational strategies pausing treatment for <2 cm lesions (TT1); downgrade in priority for recurrent although nontreatable HCCs; complete posttreatment responses of segmental portal vein thrombosis; and salvage surgery to achieve complete response in TTPR tumors (and consequent reduction in TTNT stage, etc.).

Rules apply to the system shown in Fig. 1.

^aHCC progression should be rated in order of severity as (A) progression of the treated tumor; (B) appearance of an additional nodule; (C) evidence of vascular invasion; or (D) extrahepatic tumor spread. In this model, tumor progression types A and B may indicate further treatment, upgrade in priority, or dropout depending on whether the detected progression still meets transplantation criteria; progression types C and D exclude the patient from transplantation consideration (i.e., dropout from the waiting list).