A Simple Measure of Hepatocellular Carcinoma Burden Predicts Tumor Recurrence After Liver Transplantation: The Recurrent Hepatocellular Carcinoma–Initial, Maximum, Last Classification

Abstract

Risk of recurrent hepatocellular carcinoma (rHCC) after liver transplantation (LT) depends on the pre‐LT HCC burden, tumor behavior, and response to locoregional therapy (LRT). In December 2017, LT priority for HCC was expanded to select patients outside the Milan criteria who respond to LRT. Our aims were to develop a novel objective measure of pre‐LT HCC burden (model of recurrent hepatocellular carcinoma–initial, maximum, last [RH‐IML]), incorporating tumor behavior over time, and to apply RH‐IML to model post‐LT rHCC. Using United Network for Organ Sharing data from between 2002‐2014 (development) and 2015‐2017 (validation), we identified adult LT recipients with HCC and assessed pre‐LT HCC tumor behavior and post‐LT rHCC. For each patient, HCC burden was measured at 3 points on the waiting list: initial (I), maximum (M) total tumor diameter, and last (L) exception petition. HCC burden at these 3 points were classified as (A) <Milan, (B) Milan, (C) >Milan to University of California, San Francisco (UCSF), and (D) >UCSF, resulting in each patient having a 3‐letter RH‐IML designation. Of 16,558 recipients with HCC, 1233 (7%) had any post‐LT rHCC. rHCC rates were highest in RH‐IML group CCC (15%) and DDD (18%). When M and L tumor burdens did not exceed Milan (class B or A), rHCC was low (≤10%) as in AAA, ABA, ABB, BBA, BBB; rHCC was also low (≤10%) with successful downstaging when L was A (<Milan) and M tumor burden did not exceed I, as in BBA, CCA, and DDA. In conclusion, the RH‐IML classification system is a simple summative measure of HCC burden that incorporates tumor behavior over time. RH‐IML also estimates post‐LT rHCC risk and is a useful tool for evaluating risk for rHCC post‐LT.

Non-transplantable Recurrence After Resection for Transplantable Hepatocellular Carcinoma: Implication for Upfront Treatment Choice

“…Tumor size and number have been well-recognized risk factors associated with tumor recurrence and long-term survival among patients after curative resection or transplantation for HCC. [27][28][29][30][31][32][33] In fact, both tumor size and number are surrogates of tumor aggressiveness, being strongly associated with presence of microvascular invasion, satellite lesions, and vessels that encapsulate tumor cluster. 34,35 Multifocal HCC may represent either intrahepatic metastasis or multiple primary tumors, suggesting aggressive biological behavior at the time of presentation.…”

Prognostic role of selection criteria for liver transplantation in patients with hepatocellular carcinoma: a network meta-analysis

“…Fifty-eight studies that compared the Milan criteria with other criteria were included in the study. Of these, 41 studies compared the Milan and UCSF criteria 33–45 , 47–51 , 53 , 55–60 , 63 , 64 , 67 , 68 , 70–73 , 76–79 , 83 , 85 , 86 , 90 , 16 studies compared the Milan and UPTS criteria 46 , 52 , 54 , 59 , 61 , 62 , 65 , 66 , 68 , 73 , 74 , 78 , 83 , 84 , 86 , 87 , seven studies compared the Milan and AFP criteria 69 , 75 , 80–82 , 87 , 88 , four studies compared the Milan and MT2 criteria 82 , 87–89 , one study compared the UPTS and MT2 criteria 87 , one study compared the UPTS and AFP criteria 87 , three studies compared the MT2 and AFP criteria 82 , 87 , 88 , and six studies compared the UCSF and UPTS criteria 59 , 68 , 73 , 78 , 83 , 86 .…”

Essential updates 2018/2019: Liver transplantation

“…17 Essential and the last 2-year updates of downstaging HCC before LT are summarized in Table 2. [18][19][20][21][22][23] A recent retrospective cohort of 23 and HCC-specific survival (HR 0.76 [0.59-0.98]) after LT. 18 RFA was highly beneficial for OS and HCC-specific survival after adjusting for related factors. On the other hand, the Kyoto group recently reported that any pretreatment significantly increased the recurrence rate after LT compared with no pretreatment.…”

“…The problem is that the inclusion criteria and downstaging protocols are not systematically fixed . Essential and the last 2‐year updates of downstaging HCC before LT are summarized in Table …”

“…The same group clarified the efficacy of USCF downstaging criteria compared with patients who had an initial tumor burden exceeding USCF criteria . Vutien et al advocated a useful tool for evaluating risk for recurrent HCC after LT by classifying HCC burden as Milan and UCSF criteria at initial, maximum, and last exception petition. Regarding pathological responses after LRT, complete pathological responses were significantly associated with lower post‐transplant recurrence and superior survival (5.2% vs 16% at 5‐year; P < .001) .…”