Liver Cancer (HCC) Landmark Atlas

What did the researchers want to learn?

In selected small liver cancer (3 cm or less, at most 3 nodules), is surgical removal superior to radiofrequency ablation (burning with heat) in terms of survival or recurrence-free time?

What did this study change?

In selected small liver cancer, surgery could not be shown to be superior to ablation; the choice of treatment depends on tumor location, liver reserve and the patient's condition.

Benefit for patients

Relevant to patients with early-stage HCC.

What did the research find?

The five-year survival rate was 74.6% with surgery and 70.4% with radiofrequency ablation; the five-year recurrence-free survival rate was 42.9% and 42.7%. No significant difference was shown on either measure; that is, superiority could not be proven. This result does not mean equivalence in every patient group.

Who does this apply to?

It does not prove that the two treatments are equivalent in all patient groups; it should not be generalized beyond the study selection criteria.

What did the researchers want to learn?

In liver cancer, does giving sorafenib after surgery or ablation prolong the time before the cancer comes back?

What did this study change?

It did not support routine sorafenib use after curative-intent treatment.

Benefit for patients

Relevant to patients operated for HCC.

What did the research find?

Median time before the cancer came back was 33.3 months and 33.7 months (hazard ratio 0.940); no significant benefit could be shown, that is, the main goal of the study was not met.

Who does this apply to?

Efficacy seen in advanced-stage disease cannot be automatically transferred to use after surgery.

What did the researchers want to learn?

In liver cancer, does atezolizumab + bevacizumab after surgery or ablation prolong the time before the cancer comes back, and does this benefit persist with long follow-up?

What did this study change?

Current evidence does not support routine use of atezolizumab + bevacizumab after surgery or ablation.

Benefit for patients

Relevant to patients with high-risk early HCC.

What did the research find?

A positive result was seen in the first interim analysis (hazard ratio 0.72; p=0.012). However, in the 2026 updated analysis the hazard ratio was 0.90 (95% confidence interval 0.72–1.12); the initial benefit was not maintained. Survival data are not mature.

Who does this apply to?

The first positive interim analysis does not substitute for a benefit that was not maintained at long follow-up. Subgroup signals must be confirmed in separate studies.

What did the researchers want to learn?

In advanced liver cancer that cannot be removed by surgery, does sorafenib prolong survival compared with placebo?

What did this study change?

It opened the era of systemic treatment in advanced HCC; later drugs built on this foundation.

Benefit for patients

Relevant to patients with advanced/unresectable HCC.

What did the research find?

Sorafenib prolonged survival compared with placebo. This is a historic milestone showing that systemic treatment can work in HCC (hepatocellular carcinoma).

Who does this apply to?

For advanced HCC meeting the selection criteria of that era. It does not replace today's immunotherapy era; median times should not be compared directly with modern studies.

What did the researchers want to learn?

Is the survival benefit of sorafenib also confirmed in patients with advanced liver cancer in the Asia-Pacific region?

What did this study change?

It supported the survival benefit of sorafenib in patients with different geographic and clinical characteristics.

Benefit for patients

Relevant to patients with advanced HCC.

What did the research find?

Median survival was 6.5 months with sorafenib and 4.2 months in the placebo group (hazard ratio 0.68).

Who does this apply to?

The patient group and the course of the disease differ from the SHARP study; median times from different studies should not be used directly to compare the efficacy of treatments.

What did the researchers want to learn?

In advanced liver cancer, does lenvatinib show that it is not worse than sorafenib in terms of survival?

What did this study change?

Lenvatinib became one of the first-line alternatives in suitable advanced-stage liver cancer.

Benefit for patients

Relevant to patients with advanced HCC.

What did the research find?

Median survival was 13.6 months with lenvatinib and 12.3 months with sorafenib (hazard ratio 0.92); lenvatinib was shown not to be worse in terms of survival.

Who does this apply to?

Because of exclusion criteria such as main portal vein involvement, tumor in more than half of the liver and bile duct involvement, generalization to these patients is limited.

What did the researchers want to learn?

In advanced liver cancer that cannot be removed by surgery, does atezolizumab plus bevacizumab prolong survival compared with sorafenib?

What did this study change?

It became one of the main first-line systemic treatment options for many suitable patients with advanced HCC.

Benefit for patients

Relevant to the first-line atezolizumab–bevacizumab decision in advanced HCC.

What did the research find?

Overall survival (OS) and progression-free survival (PFS) improved (updated median OS 19.2 vs 13.4 months; hazard ratio [HR] 0.66). Bevacizumab is not suitable for every patient because of bleeding / varices risk; Child-Pugh A liver function and a suitable performance status are typical.

Who does this apply to?

For unresectable HCC with no prior systemic therapy; variceal screening is critical. No head-to-head superiority claim is made over other first-line immunotherapy regimens.

What did the researchers want to learn?

In advanced or inoperable liver cancer, does a single dose of tremelimumab plus durvalumab (STRIDE) prolong survival compared with sorafenib?

What did this study change?

Using two immunotherapy drugs together created another first-line option in advanced liver cancer.

Benefit for patients

Relevant to the STRIDE (durvalumab+tremelimumab) option in advanced HCC.

What did the research find?

STRIDE median overall survival (OS) 16.4 vs 13.8 months (hazard ratio [HR] 0.78). No head-to-head superiority over atezolizumab + bevacizumab was shown.

Who does this apply to?

Superiority cannot be inferred directly versus IMbrave150 / CheckMate-9DW.

What did the researchers want to learn?

In previously untreated, inoperable liver cancer, does nivolumab + ipilimumab prolong survival compared with lenvatinib or sorafenib?

What did this study change?

It supported the first-line efficacy of dual immunotherapy; there is US approval.

Benefit for patients

Relevant to the first-line nivolumab+ipilimumab option in advanced HCC.

What did the research find?

Median overall survival (OS) 23.7 vs 20.6 months (hazard ratio [HR] 0.79). Serious immune-related side effects and liver / general condition are evaluated together. US FDA April 2025; EMA / Turkey are separate.

Who does this apply to?

Child-Pugh A; no ranking against other first-line immunotherapies; licensing in Turkey is not automatically equivalent.

What did the researchers want to learn?

Does adding durvalumab and bevacizumab to transarterial chemoembolization (TACE; blocking the vessel that feeds the tumor through a blood vessel) prolong the time before the disease progresses?

What did this study change?

It showed that TACE plus a systemic combination can improve disease control.

Benefit for patients

Relevant to the decision to add systemic therapy in TACE-candidate intermediate-stage HCC.

What did the research find?

The median time before the disease progressed (progression-free survival) was 15.0 months vs 8.2 months. This result does not mean that patients' total survival time (overall survival) was also definitely prolonged.

Who does this apply to?

Prolongation of progression-free survival does not mean prolongation of overall survival. Bleeding / toxicity and patient selection are critical.

What did the researchers want to learn?

Does adding lenvatinib and pembrolizumab to transarterial chemoembolization (TACE; blocking the vessel that feeds the tumor through a blood vessel) prolong the time before the disease progresses?

What did this study change?

It showed the potential of combining local and systemic treatment in intermediate-stage patients who are candidates for embolization; a survival benefit has not yet been proven.

Benefit for patients

Relevant to TACE-candidate HCC patients.

What did the research find?

The median time before the disease progressed (progression-free survival) was 14.6 months and 10.0 months. Prolongation of the time before progression is not the same thing as prolongation of survival.

Who does this apply to?

Side effects and patient selection must be evaluated. A direct comparison in terms of survival with the EMERALD-1 study cannot be made.

What did the researchers want to learn?

In liver cancer that has progressed after sorafenib, does regorafenib prolong survival?

What did this study change?

It showed a survival benefit in the second line after sorafenib.

Benefit for patients

Relevant to patients with advanced HCC previously treated with sorafenib.

What did the research find?

Median survival was 10.6 months with regorafenib and 7.8 months in the placebo group (hazard ratio 0.63).

Who does this apply to?

It cannot be generalized to all patients who cannot tolerate sorafenib; it applies only to selected patients who have tolerated sorafenib.

What did the researchers want to learn?

In previously treated advanced liver cancer, does cabozantinib prolong survival?

What did this study change?

It provided an additional targeted-therapy option in previously treated advanced liver cancer.

Benefit for patients

Relevant to patients with previously treated advanced HCC.

What did the research find?

Median survival was 10.2 months with cabozantinib and 8.0 months in the placebo group (hazard ratio 0.76).

Who does this apply to?

The patient group and treatment line are not exactly the same as in RESORCE; the two studies cannot be compared directly.

What did the researchers want to learn?

In liver cancer that cannot be operated on, does blocking the vessel that feeds the tumor through a blood vessel (embolization) or blocking it with drugs (chemoembolization) prolong survival compared with symptom treatment alone?

What did this study change?

It supported chemoembolization being one of the core treatments in selected inoperable liver cancer.

Benefit for patients

Relevant to early HCC surgical candidates.

What did the research find?

The study was stopped early because a survival benefit was seen. Two years later, the survival rate was 63% with chemoembolization and 27% in the control group.

Who does this apply to?

Belongs to the era before modern immunotherapy and combination treatments. It does not examine the same question as EMERALD-1 and LEAP-012.

What did the researchers want to learn?

Is embolization with drug-eluting beads (DEB-TACE) superior to conventional chemoembolization (cTACE) in tumor response?

What did this study change?

It suggested that DEB-TACE may have some safety and tolerability advantages; it cannot be said to be more effective in all patients.

Benefit for patients

Relevant to HCC patients planned for TACE.

What did the research find?

At six months, complete response was about 27% and 22%, and overall response about 52% and 44%. The prespecified superiority criterion was not met; that is, the main goal of the study was not met.

Who does this apply to?

The main superiority goal was not met. It was conducted in a context before the modern era of systemic treatment.