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The investigators sought to determine the down-staging success rate and intention-to-treat outcomes according to uniform criteria in patients with hepatocellular carcinoma.

Successful down-staging to within the Milan criteria was greater than 80% among patients with hepatocellular carcinoma (HCC), with similar efficacy when transarterial chemoembolization (TACE) and Yttrium-90 (Y-90) radioembolization were used as initial treatment, researchers reported in Gastroenterology.

The prospective, multicenter study included consecutive patients with HCC from 7 centers in 4 United Network of Organ Sharing (UNOS) regions. The investigators sought to determine the down-staging success rate and intention-to-treat outcomes according to uniform criteria (UNOS-down-staging [DS] protocol). Additionally, they assessed the influence of the type of initial down-staging treatments and other factors regarding successful down-staging.

From 2016 to 2019, consecutive patients with HCC meeting UNOS-DS eligibility criteria were enrolled and prospectively followed. A total of 209 patients were included; their median age was 63 years (interquartile range [IQR], 58-67 years), and 85.2% were men. During the first down-staging procedure, participants’ median Model for End Stage Liver Disease (MELD) score was 9 (IQR, 7-11), 75.5% were Child’s class A, and 3.0% were Child’s class C.

Among the cohort, 174 patients (83.3%) achieved successful down-staging to within the Milan criteria after a median of 2.6 months (IQR, 1.3-4.8 months); 66.1% were down-staged after 1 local regional therapy (LRT), and 33.9% needed multiple treatments. The cumulative probability of successful down-staging from the first procedure to within the Milan criteria was 67.5% at 6 months, 83.0% at 1 year, and 87.7% at 2 years.

The cumulative probability of dropout resulting from the first down-staging procedure was 22.5% at 1 year and 37.3% at 2 years. Bivariable competing risks analysis revealed that pretreatment with alpha-fetoprotein (AFP)-L3 ≥10% (subhazard ratio, 3.7; 95% CI, 1.27-10.79; P =.02) was associated with increased dropout owing to tumor progression or liver-related death, even after separate adjustment for age or AFP.

More than 90% of the cohort received either TACE (n=132) or Y-90 (n=62) as the initial down-staging treatment. The pretreatment AFP and total tumor diameter were similar in the 2 treatment groups, and no differences were observed in the modified Response Evaluation Criteria in Solid Tumors response, probability of or time to successful down-staging, or probability of waitlist dropout or liver transplant (LT).

The probability of LT at 3 years was 46.6% after a median of 17.2 months. For the explant, 17.5% had vascular invasion and 42.8% exceeded the Milan criteria.

Among the 63 patients who had an LT, the median follow-up was 1.7 years (IQR, 1.2-2.4 years), and Kaplan-Meier post-LT survival at 1, 2, and 3 years was 100%, 95.0%, and 83.1%, respectively. A total of 5 patients (7.9%) have had HCC recurrence to date, with a median time from LT to recurrence of 16.8 months (IQR, 9.7-22.3 months).

The researchers noted limitations to their findings, including the short duration of post-LT follow-up and the relatively small number of LT recipients. Additionally, referral bias is possible, as patients within down-staging criteria who received LRT in the community while also having subsequent disease progression may not have been referred for LT.

“A point of emphasis is the critical importance of precise tumor staging definitions in achieving good outcomes,” stated the investigators. “Since pre-LT viable tumor burden strongly correlates with the risk of tumor under-staging, we advocate down-staging to within Milan criteria as merely a minimal requirement for LT, and performing additional LRT until complete tumor necrosis is achieved prior to LT.”

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Mehta N, Frenette C, Tabrizian P, et al. Down-staging outcomes for hepatocellular carcinoma: results from the Multicenter Evaluation of Reduction in Tumor Size before Liver Transplantation (MERITS-LT) Consortium. Gastroenterol. Published online July 28, 2021. doi: 10.1053/j.gastro.2021.07.033