In Early Recurrent Liver Cancer, Surgery and Radiofrequency Ablation Spark Similar Survival Benefits

Because up to 70% of patients experience disease recurrence within five years after surgery to remove liver cancer, finding the best way to treat these relapses is crucial.

Recurrences of this disease are frequently found at an early stage, meaning that patients have options for treatment. But there’s uncertainty about which of the two most common treatments is more effective: additional surgery or percutaneous radiofrequency ablation (PRFA), which involves the insertion of a probe through the skin and into the tumor, where radio waves create heat to destroy the cancerous tissue.

A new study, published in JAMA Oncology, the first randomized clinical trial to compare the two methods, found no statistically significant difference between their effectiveness in prolonging survival in patients with early recurrent liver cancer, but reported that those who received PRFA versus surgery had a higher incidence of additional local or early repeat recurrence. In addition, the researchers found that patients with a slightly more advanced first recurrence got more survival benefit from surgery.

The researchers embarked on the trial because previous studies of the two treatments had been retrospective, looking back at patients’ health records to collect and compare results, and generated conflicting findings. Theirs was the first trial to randomize (divide) patients into groups and track their progress in real time.

A Head-to-Head Comparison

The trial included 240 patients with recurrent disease who otherwise were in fairly good health. Upon enrollment, all had early-stage liver cancer, defined as one cancerous nodule of 5 cm or smaller or up to three nodules, each no larger than 3 cm in diameter, with no spread of disease beyond the liver. The patients had previously been treated strictly with partial hepatectomy (surgery to remove cancerous tissue from the liver).

Mostly men with a median age of 53, the patients were divided into two groups of equal size, one of which was treated with hepatectomy while the other received ultrasound-guided PRFA. Treatment occurred between June 3, 2010 and Jan. 15, 2013.

The aim with both methods was to remove lesions with a cancer-free margin of 0.5 cm or more. Patients whose tumors were positive for cancer at the margins after removal, or who showed evidence of residual disease, received post-surgical treatment with chemoembolization, chemotherapy, radiotherapy, radioembolization, the targeted drug Nexavar (sorafenib) or interferon.

At follow-up visits, patients underwent liver function tests and abdominal ultrasounds once every two months for two years and once every three to six months thereafter. They had CT scans or MRIs at some visits, about every four to six months. Patients were followed for a median of 44.3 months.

The primary goal of the trial was to measure overall survival (OS), meaning the interval from randomization to death from any cause. Secondary goals were to measure repeat recurrence-free survival (RRFS, the interval from randomization to the first repeat recurrence of liver cancer or death, whichever came first); patterns of repeat recurrence (including timing, subtype, size and location); and therapeutic safety.

Data collected in the trial was analyzed in 2018.

Drawing Conclusions

The research team compared data gathered at one, three and five years after randomization for each patient.

In the intention-to-treat population (all the patients randomized), the one-, three- and five-year OS rates were 92.5%, 65.8% and 43.6%, respectively, for the repeat hepatectomy group and 87.5%, 52.5% and 38.5%, respectively, for the PRFA group. For the repeat hepatectomy and PRFA groups, the median OS was 47.1 months versus 37.5 months. There was no statistically significant difference in the five-year OS rate between the two groups.

In the repeat hepatectomy and PRFA groups, the median RRFS was 38.9 months versus 25.8 months. The one-year, three-year and five-year RRFS rates were 85.0%, 52.4% and 36.2%, respectively, for the repeat hepatectomy group and 74.2%, 41.7% and 30.2%, respectively, for the PRFA group.

Those assigned to PRFA compared with surgery were more likely to experience local repeat recurrence (37.8% versus 21.7%) and early repeat recurrence (40.3% versus 23.3%).

In addition, researchers found that, for patients with a cancerous nodule larger than 3 cm in diameter or an alpha-fetoprotein (AFP) level greater than 22 ng/mL (an indicator of liver cancer’s aggressiveness), PRFA was associated with worse OS compared with repeat hepatectomy.

Surgery had a higher complication rate than did ablation (22.4% versus 7.3%). The incidence of serious or severe complications was 6% with surgical treatment versus 1.6% with PRFA, the authors reported. The median hospital stay after surgical treatment was longer than that after PRFA (eight versus three days).

“The results of the present study suggest that repeat hepatectomy is associated with better local disease control and OS than PRFA in patients with a (liver tumor) diameter greater than 3 cm or an AFP level greater than 200 ng/mL,” the authors wrote. “However, the data did not show that repeat hepatectomy was superior to PRFA for the treatment of early-stage (liver cancer). Further studies are needed on the prognostic differences after laparoscopic repeat hepatectomy versus PRFA and a more effective multidisciplinary treatment strategy for (liver cancer).”