Locally-Advanced HCC: Great Debates & Updates in GI Malignancies Debate: Locally-Advanced HCC: Surgery is Optimal Michael A. Choti, MD Department of Surgery UT Southwestern Medical Center Dallas, Texas

Disclosures Beyer Healthcare: research, consultant Bristol Mayer Squibb: research, consultant

Treatment Options for HCC CURATIVE THERAPIES: Liver Resection Liver Transplantation Tumor Ablation PALLIATIVE THERAPIES: Chemoembolization Chemotherapy Radiation Therapy

Management of HCC No cirrhosis Child A Extrahepatic Spread Locally Unresectable Resectable No cirrhosis Resectable Child A T1 or T2 (1/5 or 3/3 rule) with poor liver function (Child, B or C) Biopsy to confirm Small (<5cm) Large (>5cm) RFA PEI Palliative TACE or Systemic Chemotherapy Supportive Care TACE/Y90 Resection RFA Total Hepatectomy or Supportive Care

Operative Mortality for HCC: More Recent Series Author n % Cirr % Mort Torzilli (99) 107 60% 0% Midorikawa (99) 277 68% 0% Fong (99) 154 65% 4% Fan (99) 330 49% 6%

Results of Hepatectomy for HCC Author n 1-year surv (%) 5-year surv (%) Fong (1999) 100 83 42 Llovett (1999) 77 85 51 nl bili, no portal HT 35 91 74 Takayama (2000) 74 100 62 Arii (2000) Stage 1,<2cm 1318 96 72 Stage 1, 2-5cm 2722 95 58 Stage 2, <2cm 502 92 55 Stage 2, 2-5cm 1548 95 58 Grazi (2001) 264 86 40 Wayne (2002) 249 83 41

Milan/UNOS Criteria for Transplantation Single lesion of ≤ 5cm or 2 or 3 lesions, none > 3cm No gross vascular invasion No regional nodal or distant metastases

BCLC Staging System for HCC

BCLC Staging System for HCC A early single <5-cm or 3 nodules <3-cm each B intermediate Large, multi-nodular C advanced vascular invasion and/or extrahepatic disease

Liver Resection vs Intraarterial therapy? Framing the Debate Resectable Disease Child A Anatomically resectable Outside Milan criteria Locally Advanced Large size Multifocal disease Major vascular invasion Nodal involvement Liver Resection vs Intraarterial therapy?

Liver Resection for Multiple HCCs 367 TACE 404 BSC Retrospective cohort comparison National Taiwan University 1065 patients with multiple HCCs Ho et al. Ann Surg Onc (2009)

Resection vs TACE for Multiple HCCs: RCT 2 TUMORS >2 TUMORS

Multifocal HCC Prognosis and management can vary based on biology Satellitosis Multifocal (field defect) Intrahepatic metastases

Liver Resection for HCC Invading Major Portal and/or Hepatic Veins no portal vein involvement distal to second trunk within second trunk first branch main portal trunk

Liver Resection for HCC with Major Vein Involvement Large retrospective cohort study from Japan (94-11) Among 1523 HCC resections, major venous involvement: 153 portal vein 21 hepatic vein 13 IVC Mortality 2-5% Acceptable long-term outcome Worse survival with IVCTT Kokudo et al. J Hepatology (2014)

Liver Resection for Node Positive HCC positive hilar nodes

Potentially Resectable But Locally Advanced? Liver Resection TACE/Y-90/SRT or Liver Resection TACE/Y-90/SRT followed by Defines biology and improves patient selection Response can improve resectability

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