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

Abstract

Objectives To identify the preoperative risk factors for prediction of non-transplantable recurrence (NTR) after tumor resection for early-stage hepatocellular carcinoma (HCC) to assist in patient selection relative to upfront liver resection (LR) versus liver transplantation (LT). Methods Patients who underwent curative resection for transplantable HCC and chronic liver disease were identified from an international multi-institutional database. NTR was defined as recurrence beyond the Milan or UCSF criteria, and the preoperative risk factors of NTR were investigated. Results Among 293 patients with transplantable HCC within Milan criteria and 320 within UCSF criteria, 113 (38.6%) and 131 (40.9%) patients developed tumor recurrence, respectively. Among patients who recurred, NTR was present in 32 (28.3%) patients within Milan and 35 (26.7%) within UCSF criteria. When either Milan or UCSF criteria was adopted, three preoperative risk factors including liver cirrhosis, tumor size > 3 cm, and multiple lesions were consistently identified as risk factors associated with NTR after curative resection. By summing up the three factors, a scoring model was established and the incidence of NTR among patients with 0, 1 or ≥ 2 risk factors incrementally increased from 4.5%, 13.3% to 20.5% when Milan criteria was used, and from 4.5%, 12.4% to 33.9% when UCSF criteria was adopted. The model demonstrated very good discriminatory power on internal validation (n = 5,000) (c-index 0.689 for Milan criteria, and 0.715 for UCSF criteria). Conclusions Whereas surgical resection may be optimal first-line treatment for patients with no or one risk factor, patients with ≥ 2 risk factors should be considered for upfront liver transplantation.

Predictors of non‐transplantable recurrence in hepatocellular carcinoma patients treated with frontline liver resection

“…26 However, the fundamental premise to support this strategy is to know how many HCC recurrences are actually transplantable. In line with previous research, 9,10,[27][28][29][30][31][32] we demonstrated that, in patients with single HCC ≤5 cm receiving LR, recurrence beyond MC occurred in only 18.0% of patients at the first recurrence episode and in 30.3% at any time during the follow-up. In both cases, recurrence was classified beyond MC for HCC size/number in the majority of patients.…”

“…Some Authors demonstrated that the presence of cirrhosis, tumour multifocality and AFP levels are predictive of an increased risk of NTR. 29,31 A definite association between tumour size and risk of NTR has not been clearly demonstrated so far. Fuks et al 28 and Zhang et al 31 found that HCC size >3 cm was independently associated with NTR, while this was not confirmed by other researchers.…”

“…29,31 A definite association between tumour size and risk of NTR has not been clearly demonstrated so far. Fuks et al 28 and Zhang et al 31 found that HCC size >3 cm was independently associated with NTR, while this was not confirmed by other researchers. 29 Our study indicates that tumour size is an important determinant of both the type and the time of recurrence in patients with single HCC ≤5 cm treated with frontline LR.…”

Frontline resection or liver transplantation in patients with single‐nodule hepatocellular carcinoma

“…18 Inarecentstudy,Limaetal.trainedandinternallyvali-datedtheNTRscoreaimedtopredictnon-transplantablerecurrence inpatientswithHCCundergoingliverresection. 18 UnlikePelizzaro etal.,patientswithmorethanoneHCCnoduleenteredthestudy providedthatthetumourwasconsideredresectable.TheNTRscore combined serum alpha-fetoprotein >400 ng/mL, albumin-bilirubin grade (ALBI) and tumour burden score, thus sharing most predic-torswiththestudybyPelizzaro.HigherNTRscorewasassociated with incrementally worse 5-year non-transplantable recurrence rates(low11.3%,medium28.8%,high37.5%).Anothermulticenter study including 293 patients with early-stage HCC under Milan criteriaundergoingupfrontliverresection 19 foundunderlyingliver cirrhosis,tumourdiameterlargerthan3 cmandmultiplelesionsas riskfactorswithincrementallyworsenon-transplantablerecurrence rates: 4.5% without risk factors, 13.3% in presence of 1 risk factor,and20.5%inpresenceof2or3riskfactors.Theauthorscon-cludedthatpatientswith≥2riskfactorswouldbebettercandidates forupfrontLTinsteadofliverresection,eventhoughthereported non-transplantable recurrence rates for this subpopulation were lowerthanthatobservedinthehigh-riskgroupsofPelizzaroetal. 1 andLimaetal.…”

Prognosis of repeat hepatectomy for liver transplantable hepatocellular carcinoma recurrence after hepatectomy: A Retrospective Cohort Study with the Hiroshima Surgical Study Group of Clinical Oncology (HiSCO)

“…Risk factors for non-transplantable recurrence after hepatectomy have already been reported 11,12 . However, there are no reports on the outcomes of repeat hepatectomy for transplantable and nontransplantable recurrence.…”