Percutaneous ethanol injection safe and effective in hepatocellular carcinoma [Classics Series]

1. In a large prospective cohort of patients with hepatocellular carcinoma (HCC) and contraindications to surgical management, the use of percutaneous ethanol injection (PEI) was associated with favorable survival outcomes and few adverse events at five years.

Original Date of Publication: October 1995

This study summary is an excerpt from the book 2 Minute Medicine’s The Classics in Medicine: Summaries of the Landmark Trials, 2e (The Classics Series).

Study Rundown: First described in the mid-1980s, the use of PEI for the treatment of HCC generated significant interest in the oncology community. Though surgical resection or liver transplant have historically been the preferred means of managing HCC patients, PEI was among the first in a subset of minimally-invasive treatment modalities to show promise for patients with contraindications to surgical treatment. Advantages of PEI over surgery include the low cost, short treatment time, lack of need for general endotracheal anesthesia, and the ability to perform the procedure in the outpatient setting. The majority of early PEI trials suggested treatment efficacy and improved patient survival; however, these trials were generally small in size and tracked patient outcomes for only short post-treatment intervals, and thus their validity remained uncertain.

This trial was the first to enroll a large, prospective cohort and follow them over several years after PEI with the goal of more definitively defining the procedure’s outcomes among HCC patients. Conducted at multiple clinical sites in Italy, the trial included patients with absolute or relative contraindications to surgical management and followed them for an average of three years following PEI. Given the large but highly heterogeneous population within the trial, the authors were able to generate survival data stratified according to discrete clinical factors such as tumor size, multiplicity, and Child class. The results showed overall survival trends comparable to surgical resection, and outlined in particular how survival after PEI varied as a function of patient-specific factors, most notably Child class. The rate of major complications was low, and only one death was attributable to the procedure. With these data published, PEI became the de facto standard of care for patients with contraindications to surgery and ushered in, alongside transarterial chemoembolization, the modern era of minimally-invasive HCC therapies.

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In-Depth [case series study]: A total of 746 patients (76% men; mean age 64 years) were prospectively enrolled from nine academic medical centers in Italy. Primary enrollment criteria included a pre-enrollment diagnosis of HCC and either tumor inoperability (as defined by factors such as multiple tumor foci and advanced patients age), patient refusal of surgical intervention, or referral for non-operative management at the request of the primary treating physician. Prior to PEI, all enrolled patients underwent ultrasound and contrast-enhanced computed tomography (CT) to assess disease burden. PEI was performed without general anesthesia in the outpatient setting under ultrasound guidance in one or more sessions. Treatment efficacy was assessed at one month by ultrasound, CT, and serum alpha fetoprotein, and then by imaging at 3-6 month intervals thereafter. Kaplan-Meier survival curves were generated and stratified according to factors such as tumor size, tumor number, and Child class.

The mean follow-up time was 36 months (range 12-90 months). Cumulative five-year survival varied from 26-40% among patients with one or more HCC lesions without extrahepatic involvement, and was 47% and 29% for Child class A and B patients, respectively. Among those patients with extrahepatic disease or Child class C cirrhosis, cumulative five-year survival was 0%. Local recurrence at the site of prior PEI was noted in 17% of lesions, the majority of which were treated with repeat PEI. The 30-day mortality rate was 0%, and the overall procedure-specific mortality rate was 0.1%. Major complications such as significant bleeding occurred in 1.3% of patients. Though not formally evaluated, the average cost of PEI at the participating centers was approximately $1,000 USD, as compared to $30,000 USD for surgical resection.

Livraghi T, Giorgio A, Marin G, Salmi A, de Sio I, Bolondi L, et al. Hepatocellular carcinoma and cirrhosis in 746 patients: long-term results of percutaneous ethanol injection. Radiology. 1995 Oct 1;197(1):101–8.

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