Downstaging Outcomes for Hepatocellular Carcinoma: Results From the Multicenter Evaluation of Reduction in Tumor Size before Liver Transplantation (MERITS-LT) Consortium
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Background & aims United Network of Organ Sharing (UNOS) has adopted uniform criteria for downstaging (UNOS-DS) of hepatocellular carcinoma (HCC) before liver transplantation (LT), but the downstaging success rate and intention-to-treat outcomes across broad geographic regions are unknown.Methods In this first multiregional study (7 centers, 4 UNOS regions), 209 consecutive patients with HCC undergoing downstaging based on UNOS-DS criteria were prospectively evaluated from 2016 to 2019.Results Probability of successful downstaging to Milan criteria and dropout at 2 years from the initial downstaging procedure was 87.7% and 37.3%, respectively. Pretreatment with lectin-reactive α-fetoprotein ≥10% (hazard ratio, 3.7; P = .02) was associated with increased dropout risk. When chemoembolization (n = 132) and yttrium-90 radioembolization (n = 62) were compared as the initial downstaging treatment, there were no differences in Modified Response Evaluation Criteria In Solid Tumors response, probability of or time to successful downstaging, waiting list dropout, or LT. Probability of LT at 3 years was 46.6% after a median of 17.2 months. In the explant, 17.5% had vascular invasion, and 42.8% exceeded Milan criteria (understaging). The only factor associated with understaging was the sum of the number of lesions plus largest tumor diameter on the last pre-LT imaging, and the odds of understaging increased by 35% per 1-unit increase in this sum. Post-LT survival at 2 years was 95%, and HCC recurrence occurred in 7.9%.Conclusion In this first prospective multiregional study based on UNOS-DS criteria, we observed a successful downstaging rate of >80% and similar efficacy of chemoembolization and yttrium-90 radioembolization as the initial downstaging treatment. A high rate of tumor understaging was observed despite excellent 2-year post-LT survival of 95%. Additional LRT to reduce viable tumor burden may reduce tumor understaging.
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Successful downstaging indirectly reflects more favourable tumour biology.
“In patients with successful downstaging, which indirectly reflects more-favourable tumour biology, transplantation can be considered145,146.”
From Adjuvant and neoadjuvant immunotherapies in hepatocellular carcinoma (2024) · cites this paper as [145]
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Recent Advances in Liver Transplantation for Hepatocellular Carcinoma
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Self-citationThe Role of AFP-L3 and DCP Biomarkers in the Diagnosis and Management of Hepatocellular Carcinoma
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Upper Limits of Downstaging for Hepatocellular Carcinoma in Liver Transplantation
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Multidisciplinary approaches to downstaging hepatocellular carcinoma: present and future
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From evidence to clinical practice: Bridging the gap of new liver cancer therapies in Latin America.
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The rise of transplant oncology in primary liver cancer and metastatic disease
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Liver Transplantation for Hepatocellular Carcinoma: A Narrative Review and A Glimpse into The Future
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Updates in liver transplantation policy for patients with hepatocellular carcinoma (HCC)
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SBRT for bridging and downstaging HCC before transplant
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Management of hepatocellular carcinoma prior to liver transplantation: latest developments
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Hepatocellular carcinoma and liver transplant: What about neo- and adjuvant immunotherapy
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Hepatocellular Carcinoma Bridging and Downstaging: Advances in Locoregional Therapy
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Arterial Complications in Patients Undergoing Liver Transplantation After Previous TACE Treatment
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Optimal Liver Transplantation Criteria for Hepatocellular Carcinoma
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- Authors
- Mehta, N., Frenette, C., Tabrizian, P., Hoteit, M., Guy, J., Parikh, N., Ghaziani, T. T., Dhanasekaran, R., Dodge, J. L., Natarajan, B., Holzner, M. L., Frankul, L., Chan, W., Fobar, A., Florman, S., & Yao, F. Y.
- Affiliations
- University of California, San Francisco (US)
- Scripps Green Hospital (US)
- Icahn School of Medicine at Mount Sinai (US)
- University of Pennsylvania (US)
- California Pacific Medical Center (US)
- University of Michigan (US)
- Stanford University (US)
- Corresponding author
- Mehta, Neil
- ORCID
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2021-11
- Volume
- 161
- Issue
- 5
- Pages
- 1502-1512
- ISSN
- 0016-5085 (ISSN-L)
- PMC
- PMC8545832
- OpenAlex
- W3184850586
- Cited by
- 154
- References
- 40
- Citations by year
- 2026: 25 · 2025: 29 · 2024: 42 · 2023: 33 · 2022: 20 · 2021: 3
- FWCI
- 13.61
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Exelixis
- National Institute of Diabetes and Digestive and Kidney Diseases
- Liver Center, University of California, San Francisco
- Eli Lilly and Company
- Bayer Fund
- Eisai
- National Institutes of Health (P30 DK026743)
- Genentech
- Topics
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Renal cell carcinoma treatment
- Keywords
- hepatocellular carcinoma, tumor downstaging, liver transplantation, Milan criteria, understaging, transarterial chemoembolization, yttrium-90 radioembolization, alpha-fetoprotein, tumor size, HCC recurrence, post-transplant survival, vascular invasion
- MeSH terms
- Aged, Feasibility Studies, Female, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Male, Middle Aged, Neoplasm Recurrence, Local, Neoplasm Staging, Patient Dropouts, Prospective Studies, Risk Factors, Time Factors, United States, Waiting Lists, Liver Transplantation, Chemoembolization, Therapeutic, Treatment Outcome, Disease Progression, Risk Assessment, Radiopharmaceuticals, Tumor Burden
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