HCC is the main kind of primary liver cancer, and it usually grows in a liver already dealing with chronic inflammation, cirrhosis, hepatitis, alcohol damage, or metabolic disease. In other words, the neighborhood is messy before the villain even arrives.
That matters because surgery can remove the main mass, but it cannot guarantee that stray cancer cells have not already scattered. Those microscopic leftovers are the whole horror movie plot.
Enter Perioperative Immunotherapy, Which Means "Around Surgery"
The JHEP Reports piece by Aceituno and Vogel is a commentary on the CARES-009 trial, and the lesson is fairly crisp: maybe the best moment to use immunotherapy is not only after surgery, but before and after it (Aceituno and Vogel, 2026).
Why before? Because an intact tumor is basically a giant, ugly wanted poster. If you give immunotherapy while the tumor is still in place, your immune system gets to see the full criminal lineup before the building disappears.
In CARES-009, patients with resectable HCC at intermediate or high risk of recurrence were randomized to surgery alone or to perioperative treatment with camrelizumab, a PD-1 blocker, plus rivoceranib, a VEGFR2 inhibitor, wrapped around surgery. The regimen improved event-free survival, with a median of 42.1 months versus 19.4 months for surgery alone, and a hazard ratio of 0.59 (Qin et al., 2025).
That is not a subtle shrug. That is a real signal.
Why This Is Interesting, Beyond "Numbers Went Up"
The logic is appealing in a way cancer biology rarely allows. Camrelizumab takes the brakes off T cells. Rivoceranib helps by blocking tumor blood-vessel signaling, which can also make the microenvironment a little less hostile to immune attack. Think fewer escape tunnels, more bodyguards getting inside.
And timing seems to matter. A 2024 patient-level analysis across neoadjuvant ICI studies in HCC found that deeper pathological responses after preoperative immunotherapy were linked with better relapse-free survival (D'Alessio et al., 2024; PMCID: PMC12040480). Translation: if the tumor looks badly damaged under the microscope after pre-op treatment, that tends to be a good sign later. Science loves a preview trailer.
Before We Start High-Fiving the Liver Team
There is a reason experts are still cautious. Adjuvant immunotherapy in HCC has been messy.
The phase 3 IMbrave050 trial initially suggested that atezolizumab plus bevacizumab after curative treatment could reduce recurrence risk (Qin et al., 2023). Then the updated analysis cooled the excitement, and the benefit did not hold up the way people hoped (Yopp et al., 2026). KEYNOTE-937, testing adjuvant pembrolizumab, also failed to improve recurrence-free survival in its 2026 readout.
So the CARES-009 story is not "immunotherapy solved recurrence." It is more specific, and more useful: perioperative strategy may work better than adjuvant-only strategy. That is a much smarter sentence.
What This Could Mean for Actual Humans
If these results hold up across broader populations, perioperative immunotherapy could turn liver cancer surgery from a one-and-done gamble into a more coordinated campaign. Hit the tumor before surgery. Remove what remains. Keep pressure on afterward.
For patients, that could mean fewer recurrences, longer stretches without cancer returning, and maybe a real shift in what "curative-intent" treatment actually delivers. Not bad for a field that has spent years watching HCC come back like a villain in a franchise with too many sequels.
Still, there are real caveats. CARES-009 was done in China, where patient characteristics, staging patterns, viral hepatitis burden, and treatment pathways can differ from Western practice. Toxicity matters. Liver reserve matters. Picking the right patients matters a lot, because immunotherapy in a fragile cirrhotic liver is not casual business.
That is why the current mood is not victory-lap, confetti-cannon optimism. It is something better: disciplined interest. The rare kind that survives contact with follow-up data.
References
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Aceituno L, Vogel A. Perioperative immunotherapy to reduce recurrence in resectable hepatocellular carcinoma - lessons learned from the CARES-009 trial. JHEP Reports. 2026. DOI: 10.1016/j.jhepr.2026.101820
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Qin S, et al. Perioperative camrelizumab plus rivoceranib versus surgery alone in patients with resectable hepatocellular carcinoma at intermediate or high risk of recurrence (CARES-009): a randomised phase 2/3 trial. The Lancet. 2025. DOI: 10.1016/S0140-6736(25)01720-9
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D'Alessio A, Stefanini B, Blanter J, et al. Pathological response following neoadjuvant immune checkpoint inhibitors in patients with hepatocellular carcinoma: a cross-trial, patient-level analysis. The Lancet Oncology. 2024;25(11):1465-1475. DOI: 10.1016/S1470-2045(24)00457-1. PMCID: PMC12040480
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Qin S, Chen M, Cheng AL, et al. Atezolizumab plus bevacizumab versus active surveillance in patients with resected or ablated high-risk hepatocellular carcinoma (IMbrave050): a randomised, open-label, multicentre, phase 3 trial. The Lancet. 2023;402(10415):1835-1847. DOI: 10.1016/S0140-6736(23)01796-8
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Yopp A, Chen M, Cheng AL, et al. Updated data from IMbrave050: Adjuvant atezolizumab plus bevacizumab for high-risk hepatocellular carcinoma. Journal of Hepatology. 2026. DOI: 10.1016/j.jhep.2026.01.006
Disclaimer: The image accompanying this article is for illustrative purposes only and does not depict actual experimental results, data, or biological mechanisms.