Better Long-Term Prognosis: Comparison Between Surgery and TACE as Initial Treatment for Operable Huge HCCs (≥10 cm) After More Than 5 Years of Follow Up

Surgical treatment for hepatocellular carcinoma (HCC), including liver resection and transplantation,¹ is the first therapeutic choice for the cancers. However, patients with HCC ≥10 cm often are treated with nonsurgical approaches because of the presumed higher risks associated with surgery.² However, the reported 5-year survival rate after transarterial chemoembolization (TACE) for very large HCCs is only 7% to 10%.^3–5 Thus, liver resection appears to be associated with better prognosis than TACE, with 5-year survival rates reaching 35%.^5,6 However, few data are available on the long-term survival of patients with very large HCCs treated with surgical resection compared directly with TACE.

In this study, we proposed to determine the long-term outcome of patients with HCC ≥10 cm treated with surgical resection or TACE. We also analyzed risk factors for disease-specific overall survival after the 2 treatments.

Materials and Methods

Results

Clinical features and tumor characteristics of the 2 groups of patients are summarized in Table 1. No differences between the hepatic resection group and the TACE group were identified. The diseased-specific overall survival curves of the 2 patient groups are illustrated in Fig. 1. The median survival time was significantly longer in the resection group than in the TACE group (30.2 versus 9.33 months; P = 0.05). The 1-, 3-, and 5-year survival rates for patients in the resection group were 57.8%, 36.1%, and 28.9%, respectively, which were significantly better than for patients in the TACE group (1-, 3-, and 5-year survival rates of 33.3%, 11.1%, and 0, respectively). Most patients in the TACE group died within 20 months, but 1 patient, who underwent palliative hepatic resection after 3 courses of TACE, survived 57 months.

Table 1 Clinical features of the hepatic resection group and the TACE group

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The details of the 16 patients in the surgical group are listed in Table 2. In summery, patient age was between 34 and 79 years. Most of the tumors were located at the right lobe (13 of 16). Most of them were a single tumor. The tumor size was between 10 and 18 cm. The only mortality was caused by liver failure. There were 4 morbidities including pneumonia in 2 patients and bile leakage in 2 patients. The follow-up period was between 0.2 and 83.2 months. Only 1 patient was still free of recurrence after a 73.1-month follow-up period. Most recurrences were located in the liver. However, 6 of them were combined with extrahepatic recurrence including the lung (5 patients) and spleen (1 patient). Most of the patients with recurrence received TACE as their primary treatment. Only 1 patient received re-resection and was still alive after an 83.2-month follow-up.

Table 2 Details of patient of operation group

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Table 2 Extended

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We analyzed prognostic factors for the 25 HCC patients (Table 3). Univariate analysis identified 3 negative prognostic factors for overall survival including age <50 years, preoperative portal vein thrombosis, and TACE.

Table 3 Prognostic factors for patients with HCC ≥10 cm

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Discussion

This study had 2 objectives: (1) determine the long-term outcome of patients with HCC ≥10 cm treated with surgical resection compared with TACE and (2) analyze risk factors for disease-specific overall survival after the 2 treatments.

Previous studies had suggested that resection is superior to TACE in the treatment of very large HCCs, but ours is the first study to our knowledge that directly compared the 2 treatments with follow-up for as long as 5 years. Min et al.⁷ directly compared the prognosis between surgery and TACE and found significantly higher 1-, 2-, and 3-year overall survival rates for operated patients than for TACE-treated patients followed for a median time of 14.5 months. Other studies have reported that the 5-year survival rate of patients with HCCs ≥10 cm who underwent surgical interventions varied from 16.7% to 54.0%,^2,5,8–12 whereas the reported 5-year survival rate of TACE-treated patients for similarly large HCCs is less than 10%.^3,4 Yamashita et al.⁵ and Mok et al.¹³ have reported that the 5-year survival rate in patient with HCC ≥10 cm who had resection was significantly better than in those who did not have resection.

We first found that patients who had surgical resection had a significantly better overall survival that did patients treated with TACE (median survival, 30.2 versus 9.33 months; P = 0.05). Survival rates at 1, 3, and 5 years also were superior in the patients who had resection (1YOS: 57.8% versus 33.3%, 3YOS: 36.1% versus 11.1%, and 5YOS: 28.9% versus 0). The 2 patient groups were well matched for age, sex, comorbidity, hepatitis virus type, liver function, tumor characteristics, and tumor stage. Most patients in the TACE group died within 20 months. Only 1 patient in the TACE group who survived more than 20 months received surgery following the first TACE treatment. Therefore, we considered that tumor resection is still the best treatment policy for huge HCCs. Surgeons should carefully evaluate these patients. Once the patient was fit for surgery, surgical resection should be done for the best prognosis for patients.

However, another concern is perioperative morbidity and mortality. The technical demand is higher for resection of huge HCCs, and the following mortality and morbidity rates may be possibly higher than surgical resection for smaller HCCs. The reported mortality for resection of HCCs ≥10 cm is 2% to 15%,^5–7 and the complication rates were about 24.5% to 50%.^5,6 Previously, our group compared surgical results including postoperative mortality, incidence, and severity of morbidity between operation for huge HCC and smaller (less than 10 cm) HCCs.¹⁴ Although higher perioperative stress included longer operative time, more blood loss, and more blood transfusions, there was no difference in perioperative mortality or rates and severity of complications between surgery for huge HCCs or smaller HCCs. In our opinion, although resection is technically demanding, the mortality and morbidity rates in patients operated for HCC ≥10 cm compare favorably with those operated for HCCs <10 cm.

Our study has limitations. First, it is a retrospective nonrandomized study, and the choices of TACE or surgery were based on surgeons' evaluation and the patients' clinical condition. Second, the sample size is relatively small. Despite the small size, however, the survival difference between the TACE group and surgical group is significant. Moreover, the length of follow-up time for our study is more than 5 years. The follow-up period of a previously published similar study⁷ is 3 years. Further larger sample, multicenter, and even randomized control trials are necessary to corroborate the findings here.

Conclusions

We conclude that surgical resection for HCCs ≥10 cm appears superior to TACE as it provides a higher rate of longer long-term survival. Although resection is technically demanding, the operation is still safe for selected patients. Patients, especially young patients, with advanced-stage tumors and unfavorable biological behavior of the tumor should not necessarily be excluded from undergoing liver resection with the possibility of a cure. However, larger series should be studied to validate our results.