Adjuvant immunotherapy after curative-intent treatment for hepatocellular carcinoma: evidence, limitations, and a research framework for molecular residual disease-guided intervention-a narrative review.
- 1Department of Hepatobiliary Surgery, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Abstract
Recurrence remains common after curative-intent treatment of hepatocellular carcinoma (HCC). Immune checkpoint inhibitors (ICIs), which are effective in advanced disease, have been evaluated empirically in patients with no radiologic evidence of tumor. The initial recurrence-free survival (RFS) advantage in IMbrave050 (NCT04102098) was not maintained with longer follow-up, and KEYNOTE-937 (NCT03867084) was negative. This review examines the limits of clinicopathologic risk selection and the potential role of molecular residual disease (MRD) in postoperative treatment decisions. PubMed/MEDLINE, ClinicalTrials.gov, selected journal websites, and the American Society of Clinical Oncology and European Society for Medical Oncology meeting abstract repositories were searched for English-language reports from 1 January 2015 to 1 July 2026. Concepts included HCC, curative-intent treatment, adjuvant or perioperative immunotherapy, circulating tumor DNA (ctDNA), liquid biopsy, and MRD. Earlier landmark studies were traced from references. Guidelines, randomized trials, prospective cohorts, and translational studies were prioritized; non-HCC evidence was used only for methodology or trial design. Imaging-defined absence of tumor encompasses eradication of the index tumor, occult index-tumor-derived disease, and persistent liver-field risk for a new primary HCC. Clinicopathologic features estimate group-level recurrence risk but do not establish an individual's residual-disease state or ICI susceptibility. Updated IMbrave050 and reported KEYNOTE-937 results do not support routine empirical adjuvant ICI, although a phase II sintilimab trial reported benefit in patients with microvascular invasion. In CARES-009 (NCT04521153), resection was achieved in 92% versus 98%, and grade ≥ II surgical complications occurred in 35% versus 16%; the contribution of postoperative treatment cannot be isolated. Post-treatment ctDNA positivity is associated with poorer recurrence outcomes, but prediction of ICI benefit and utility of ctDNA-guided care remain unproven in randomized HCC trials. A nondetected result is informative only when input, assay quality, and baseline trackability are adequate. Future postoperative trials should integrate evidence of residual disease and treatment susceptibility with liver-related and treatment-related risks. Routine adjuvant ICI and treatment allocation based on MRD alone are not supported until biomarker-stratified randomized trials establish clinical utility.
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BibTeX
@article{bai2026adjuvant,
title = {{Adjuvant immunotherapy after curative-intent treatment for hepatocellular carcinoma: evidence, limitations, and a research framework for molecular residual disease-guided intervention-a narrative review.}},
author = {Bin Bai and Xian Su and Feilong Zhou and Haibei Xin and Minfeng Zhang},
journal = {Journal of gastrointestinal oncology},
year = {2026},
month = sep,
doi = {10.21037/jgo-2026-0810},
url = {https://europepmc.org/article/MED/42996872},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Adjuvant immunotherapy after curative-intent treatment for hepatocellular carcinoma: evidence, limitations, and a research framework for molecular residual disease-guided intervention-a narrative review.
AU - Bin Bai
AU - Xian Su
AU - Feilong Zhou
AU - Haibei Xin
AU - Minfeng Zhang
PY - 2026
DA - 2026/09/29
JO - Journal of gastrointestinal oncology
DO - 10.21037/jgo-2026-0810
UR - https://europepmc.org/article/MED/42996872
AB - Recurrence remains common after curative-intent treatment of hepatocellular carcinoma (HCC). Immune checkpoint inhibitors (ICIs), which are effective in advanced disease, have been evaluated empirically in patients with no radiologic evidence of tumor. The initial recurrence-free survival (RFS) advantage in IMbrave050 (NCT04102098) was not maintained with longer follow-up, and KEYNOTE-937 (NCT03867084) was negative. This review examines the limits of clinicopathologic risk selection and the potential role of molecular residual disease (MRD) in postoperative treatment decisions. PubMed/MEDLINE, ClinicalTrials.gov, selected journal websites, and the American Society of Clinical Oncology and European Society for Medical Oncology meeting abstract repositories were searched for English-language reports from 1 January 2015 to 1 July 2026. Concepts included HCC, curative-intent treatment, adjuvant or perioperative immunotherapy, circulating tumor DNA (ctDNA), liquid biopsy, and MRD. Earlier landmark studies were traced from references. Guidelines, randomized trials, prospective cohorts, and translational studies were prioritized; non-HCC evidence was used only for methodology or trial design. Imaging-defined absence of tumor encompasses eradication of the index tumor, occult index-tumor-derived disease, and persistent liver-field risk for a new primary HCC. Clinicopathologic features estimate group-level recurrence risk but do not establish an individual's residual-disease state or ICI susceptibility. Updated IMbrave050 and reported KEYNOTE-937 results do not support routine empirical adjuvant ICI, although a phase II sintilimab trial reported benefit in patients with microvascular invasion. In CARES-009 (NCT04521153), resection was achieved in 92% versus 98%, and grade ≥ II surgical complications occurred in 35% versus 16%; the contribution of postoperative treatment cannot be isolated. Post-treatment ctDNA positivity is associated with poorer recurrence outcomes, but prediction of ICI benefit and utility of ctDNA-guided care remain unproven in randomized HCC trials. A nondetected result is informative only when input, assay quality, and baseline trackability are adequate. Future postoperative trials should integrate evidence of residual disease and treatment susceptibility with liver-related and treatment-related risks. Routine adjuvant ICI and treatment allocation based on MRD alone are not supported until biomarker-stratified randomized trials establish clinical utility.
SN - 2078-6891
SN - 2219-679X
ER -