Focus on Treatment of Large Hepatocellular Carcinoma

Abstract

In this issue of Annals of Surgical Oncology, Wu et al.1 present an initial experience with extracorporeal high intensity focused ultrasound (HIFU) for treatment of patients with cirrhosis and unresectable hepatocellular carcinoma (HCC). Fifty-five patients with predominantly large HCC (only 2/55 had tumors 5 cm) who were considered unresectable (only 4 were considered resectable but refused surgery) were studied; 38% were treated with HIFU because of “failure” of transarterial chemoembolization (TACE). Complications were minor and uncommon, and the 18-month survival rate was 35%. This analysis highlights two areas worthy of further discussion: treatment selection for all patients with large HCC, and advances and limitations of locoregional therapies for unresectable HCC. Morphologic criteria such as tumor size do not accurately predict outcome following surgical treatment of HCC. Despite the association between tumor size and vascular invasion, (one of the strongest determinants of survival), the International Union Against Cancer (UICC) / 6th Edition American Joint Committee on Cancer (AJCC) staging for liver cancer confirms that median survival exceeds 5 years following resection of large solitary tumors (5–10 cm and even 10 cm) without vascular invasion (T1 tumors). This staging system was validated and this specific finding confirmed by Poon et al. in Chinese patients with HCC in a background of Hepatitis B,2 which is pertinent to the study population in the present report. With regard to patients with large tumors, transplantation, TACE and local tumor ablation are usually contraindicated based on existing criteria,3–5 which leaves hepatic resection as the sole treatment shown to provide long-term survival for selected patients in this group.6–9 Lee et al. reported 1-, 3-, and 5-year disease-free survival rates of 42%, 30%, and 28%,7 and Zhou et al. described a 26% 5-year survival rate for patients with tumors equal to or greater than 10 cm; over 17% of patients were alive at 10-years of follow-up in their report.9 Because underlying liver disease compromises posthepatectomy liver function, many patients with technically resectable tumors may not be candidates for safe major hepatic resection. Patients with Child-Pugh A cirrhosis and no portal hypertension may benefit from preoperative portal vein embolization in order to reduce the complications associated with inadequate function of the post-resection liver remnant10 and the risk of death from liver failure.11,12 Despite such advances in preoperative preparation, even when combined with technical advances in surgery, anesthesia and postoperative care, the majority of patients that present with large HCC are not candidates for potentially curative therapy due to tumorrelated factors such as major vascular invasion or to liver factors such as extensive underlying fibrosis. Interpretation of outcome data from tumor ablation studies is difficult for reasons described above—morphologic criteria alone do not accurately predict prognosis for HCC. The natural history of patients with untreated HCC varies widely, with median survival which can range from less than 6 months to 20 months, and estimated tumor doubling time which can range from 1 month to 19 months.13 Further, no rigorous evidence exists to suggest that local tumor ablation provides recurrence-free or overall survival equivalent to hepatic resection for any hepatic tumor (including the most studied technique of ablation, RFA)14,15 whereas RFA has been shown to be associated with inferior disease-free and overall survival compared to resection in patients with cirrhosis and resectable HCC.15 RFA is usually limited to treatment of tumors smaller than 4–6 cm because of the nearly uniform recurrence (persistence) of Received September 20, 2004; accepted October 18, 2004. Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas. Address correspondence to: Eddie K. Abdalla, MD, Assistant Professor of Surgery, Department of Surgical Oncology, Unit 444, The University of Texas M. D. Anderson Cancer Center, PO Box 301402, 1515 Holcombe Boulevard, Houston, Texas 77230-1402; Fax: 713745-1921; E-mail: eabdalla@mdanderson.org