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Liver resection should be the primary therapeutic option for patients with early multinodular hepatocellular carcinoma (HCC) who are ineligible for transplant, a retrospective cohort study suggested.

In this cohort of 720 patients, a multivariable Cox model of overall survival (OS) in a matching-adjusted indirect comparison (MAIC)-weighted population showed that percutaneous radiofrequency ablation (PRFA) and transarterial chemoembolization (TACE) had higher risks of mortality compared with liver resection:

• PRFA: HR 1.41, 95% CI 1.07-1.86, P=0.01
• TACE: HR 1.86, 95% CI 1.29-2.68, P=0.001

After MAIC weighting, 1-, 3-, and 5-year survival rates were 89.11%, 70.98%, and 56.44% with liver resection; 94.01%, 65.20%, and 39.93% with PRFA; and 90.88%, 48.95%, and 29.24% with TACE, reported Alessandro Vitale, PhD, MD, of the University of Padua in Italy, and colleagues in .

Median OS was 69 months for patients who had liver resection, 54 months for those who had PRFA, and 34 months for those who had TACE.

"This clear superiority of LR [liver resection] over nonsurgical therapies in patients with early multinodular HCC is at variance from three previous studies indicating a clear superiority of LR only for RFS [recurrence-free survival]," wrote Vitale and colleagues. "However, as these results are robustly supported by an adequately large sample size and by the use of the MAIC technique that reduced the selection bias in comparing treatment groups, the findings of this study are more probative than the previous ones."

In explaining the rationale behind the study, the authors noted that suggest evaluating liver resection before other therapies in all patients with HCC and compensated cirrhosis without extrahepatic metastases, irrespective of vascular invasion, tumor size, and number of nodules, while the updated states that when transplant is not feasible, PRFA is recommended, and if this is not feasible, TACE is recommended, excluding liver resection as a therapeutic approach.

In addition, "although a large amount of solid indirect evidence suggests the superiority of LR over PRFA or TACE regardless of Barcelona Clinic Liver Cancer stage, direct evidence comparing these three treatments in the subgroup of early multinodular HCC is relatively poor," Vitale and team observed. "Based on these premises, an observational study on this topic is justified."

In an , Yuman Fong, MD, and Jonathan Kessler, MD, both of the City of Hope Cancer Center in Duarte, California, said the clinical situation involving the treatment of early multinodular HCC "is usually much more complicated than deciding which of these 3 suitable local therapies is best," and most patients in clinical practice will likely receive more than one therapy unless cured.

For example, "most patients on recurrence will have additional local therapies, which could range from embolization of multifocal disease to re-resection or transplant for solitary lesions," they wrote. They also pointed out it is increasingly likely that surgery will be used with percutaneous ablation for patients with multifocal disease involving peripheral and deep lesions -- percutaneous ablation for deep lesions and minimally invasive laparoscopic or robotic liver resection for superficial lesions.

"All of our local therapies are getting better," Fong and Kessler added. "Making each available under different clinical circumstances and combining these when appropriate provides patients with the best chance at cure with the least invasiveness."

This study used data from two Italian databases -- one for liver resection and the other for PRFA and TACE -- that included patients from multiple centers from 2008 to 2020.

Of the 720 included patients, 75.4% were men, and 48.6% were older than 70; 296 patients underwent a liver resection, 240 underwent PRFA, and 184 underwent TACE.

Liver resection included anatomic (38.18%), major (6.76%), and laparoscopic (30.74%) cases.

Vitale and colleagues also conducted competing risk-weighted and subgroup survival analyses, and found that in patients with Child-Pugh class B cirrhosis, OS was significantly better with liver resection compared with TACE (HR 2.79, 95% CI 1.56-5.00, P=0.001), but there was no significant difference compared with patients undergoing PRFA (HR 1.44, 95% CI 0.82-2.54, P=0.21).

Patients who underwent liver resection also had a numerically lower risk of HCC-related death than those who underwent PRFA or TACE, but there was no difference in non-HCC-related deaths.

In addition, a subgroup analysis of the 318 patients undergoing only first-line therapy showed that liver resection led to significantly better survival compared with PRFA and TACE.

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