Combined Chemoembolization and Ablation Effective for Early Stage Hepatocellular Carcinoma

(Reuters Health) - Transcatheter arterial chemoembolization combined with radiofrequency ablation works better as an initial treatment for early-stage hepatocellular carcinoma than radiofrequency ablation alone, a new study suggests.

For the study, researchers examined long-term data on 189 clinical trial participants with early-stage hepatocellular carcinoma who had been randomized 1:1 to receive either radiofrequency ablation (RFA) alone or two weeks after receiving transcatheter arterial chemoembolization (TACE). The primary endpoints were overall survival and recurrence-free survival, with a median follow-up period of 56 months in the combination therapy group and 50 months for the group that only received RFA.

Overall survival rates at five years were 52.0% for the TACE and RFA combination therapy group, compared to 43.2% with RFA alone. At seven years, overall survival was 36.4% with combination therapy compared to 19.4% with monotherapy.

Similarly, five-year recurrence-free survival rates were 41.4% with the combination of TACE and RFA, compared to 27.4% with RFA alone. And at seven years, recurrence-free survival rates were 34.5% with combination therapy compared to 18.1% with monotherapy.

There are several reasons combination therapy may be more effective, said senior study author Dr. Zhen-Wei Peng of the department of radiation oncology at the First Affiliated Hospital and Sun Yat-sen University in Guangzhou, China.

"As TACE before RFA decreases blood flow to the tumor from the hepatic artery, it reduces the 'heat sink' effect with resultant increase in the extent of the RFA-induced coagulation zone," Dr. Peng said by email.

TACE also decreases the chance of incomplete ablation, which is a prognostic factor for overall survival after RFA, by eliminating any existing micro-metastases or microvascular invasion through embolization and chemotherapy, Dr. Peng added. TACE also increases the extent of the zone of ablative necrosis by RFA because TACE induces ischemia and inflammation in the treated tumor and its surrounding tissues, Dr. Peng said.

Patients' mean age at baseline was 54.3 years. To be included in the study, they could have a single hepatocellular carcinoma up to 7 cm in diameter or multiple hepatocellular carcinomas up to 3 cm in diameter. People with radiologic evidence of invasion into major portal or hepatic venous branches or extrahepatic metastases were excluded.

In subgroup analysis, recurrence-free survival rates were significantly higher with TACE and RFA combined than with RFA alone for patients with tumors larger than 3 cm (HR 2.03).

Recurrence-free survival was also significantly higher in the combination therapy group for individuals under 60 years old (HR 1.64) and for patients with a single tumor (HR 1.51), the study found.

Beyond its small size, other limitations of the study include having been done at a single center and that fact that results from Chinese patients might not be generalizable to patients elsewhere.

Even so, a 3 cm tumor diameter has previously been shown to be the limit beyond which RFA alone doesn't work optimally for hepatocellular carcinoma, said Dr. Fabio Piscaglia, a professor of internal medicine at the University of Bologna in Italy who wasn't involved in the study.

"It is not surprising that in the study patient population the combination of RFA with TACE works better than RFA alone, because the majority of the study population was suffering from tumors larger than 3 cm, which is known to not achieve a complete response, at least at a microscopic level," Dr. Piscaglia said by email. "This study does not bring convincing evidence that it is worth using the combination in all early-stage tumors including those smaller than 3 cm."

SOURCE: https://bit.ly/3F3Ux3T JAMA Network Open, online September 27, 2021.