Liver metastases from stomach cancer: what they mean, how they are treated, and what is the prognosis?

Liver metastases from stomach cancer mean that tumor cells have spread from the stomach to a distant organ. In the international TNM staging system, this corresponds to stage M1 and stage IV gastric cancer, regardless of the size of the primary tumor and the number of affected regional lymph nodes. Metastatic lesions in the liver remain gastric cancer cells—they are not "new liver cancer." [1]

This is a serious stage of the disease, but the presence of metastases does not mean the absence of treatment. The mainstay of therapy for most patients is systemic treatment—chemotherapy combined with immunotherapy or targeted drugs based on HER2, PD-L1, MSI/MMR, and CLDN18.2. Current guidelines require determining these biomarkers in unresectable or metastatic gastric cancer, as they directly influence the choice of first-line treatment. [2]

Liver surgery is not standard for most patients with stage IV disease. However, a rare situation exists: a solitary liver metastasis without other distant lesions. The 2025 Japanese guidelines allow for surgical removal of such a metastasis as a weak recommendation in the absence of other factors for unresectability, while ESMO emphasizes that resection of metastases should not be recommended routinely and should only be considered in carefully selected patients with oligometastatic disease. [3]

Liver metastasis and gastric cancer spreading to the liver are not the same thing.

This is a fundamentally important distinction.

If a stomach tumor directly invades adjacent liver tissue, it is considered local invasion T4b. If there are no distant metastases, the disease may remain stage III. [4]

A completely different situation occurs when a separate lesion forms in the liver tissue, not a continuation of the primary gastric tumor. This is called hematogenous distant metastasis (M1).

At M1, gastric cancer is classified as stage IV regardless of T and N. [5]

Situation	TNM meaning	Possible stage
A stomach tumor directly invades the adjacent liver.	T4b, but M0	It could be stage III.
A separate tumor node in the liver	M1	Stage IV
Several isolated foci in the liver	M1	Stage IV
Metastases simultaneously in the liver and other organs	M1	Stage IV

This distinction is also important for treatment: potentially radical surgery for T4bM0 and the treatment strategy for true M1 are significantly different.

Why does stomach cancer spread to the liver?

The liver is one of the typical sites for distant spread of gastric cancer. The NCI classifies the liver, lungs, and peritoneum as typical sites for metastasis. [6]

One of the reasons is related to circulatory issues. A significant portion of the blood from the gastrointestinal tract flows through the portal vein to the liver. Tumor cells entering the venous circulation from the primary tumor can thus reach the liver, become trapped in its capillary network, and form secondary lesions. The American Cancer Society specifically notes that gastrointestinal tumors are particularly prone to spread to the liver precisely because of the direction of blood flow from the digestive organs. [7]

However, the entry of a tumor cell into the bloodstream does not guarantee metastasis. For this to occur, the cell must survive the circulation, penetrate the liver tissue, adapt to the new microenvironment, stimulate vessel formation, and begin dividing.

Therefore, the development of metastatic disease depends not only on the size of the primary tumor, but also on its biological characteristics.

What are synchronous and metachronous metastases?

Synchronous metastases are those detected simultaneously with primary gastric cancer or during initial staging.

Metachronous metastases appear later - for example, some time after gastrectomy performed for initially non-metastatic disease.

This distinction has clinical significance. In studies of patients undergoing surgical removal of metastases, metachronous liver lesions have often been associated with more favorable outcomes than synchronous lesions. However, these data were obtained primarily in carefully selected surgical groups and do not imply that the timing of metastasis on its own determines prognosis. [8]

A metachronous solitary lesion after a long period without signs of disease may indicate a less aggressive tumor biology than multiple liver metastases detected simultaneously with spread to the peritoneum and lungs.

How many metastases can there be in the liver?

The picture can be very different:

• one small metastasis;
• several foci in one lobe;
• metastases in both lobes;
• dozens of small foci;
• large metastatic conglomerate;
• liver damage simultaneously with the peritoneum, lungs, bones or distant lymph nodes.

The number and distribution of lesions fundamentally influence the possibility of local treatment.

The most unusual and potentially favorable situation is a solitary metastasis, that is, a single metastasis without other distant foci. It is for this small group that Japanese guidelines allow surgical treatment with strict selection. [9]

In multiple bilateral metastases, systemic treatment is almost always the mainstay of therapy.

What are the symptoms of liver metastases?

Small metastases may not cause any symptoms at all. Metastatic cancer can generally remain asymptomatic for a long time, and symptoms depend on the size and location of the lesions. [10]

Therefore, metastases are often first detected on CT scans during gastric cancer staging or follow-up examinations after treatment.

With an increase in tumor load, the following may appear:

• loss of appetite;
• weakness and fatigue;
• weight loss;
• discomfort or pain on the right side under the ribs;
• abdominal enlargement;
• ascites;
• jaundice;
• itchy skin;
• swelling of the legs. [11]

The American Cancer Society also lists jaundice as a possible symptom of stomach cancer that has spread to the liver.[12]

But the absence of jaundice or pain does not exclude metastases.

Why does jaundice usually not appear immediately?

The liver has a large functional reserve. One or more small tumor nodules may not interfere with its function for a long time, causing noticeable clinical symptoms.

Jaundice often appears with a significant tumor load or with a violation of the outflow of bile.

The NCI and the American Cancer Society list yellowing of the skin and sclera and abdominal distension as possible manifestations of liver metastases. [13]

So the logic is:

"Bilirubin is normal, meaning there are no liver metastases."

Incorrect.

To detect metastases, imaging is used, not just blood chemistry.

How are liver metastases detected?

The main study in staging gastric cancer is contrast-enhanced computed tomography of the chest, abdomen and pelvis.

ESMO recommends this complex in the initial staging, in addition to gastroscopy, blood tests and assessment of liver and kidney function. [14]

CT allows us to determine:

• number of suspicious lesions;
• their sizes;
• location;
• lymph node damage;
• the presence of metastases in other organs;
• signs of peritoneal spread.

The American Cancer Society notes that CT scanning for stomach cancer can detect spread to the liver and is used for staging and treatment planning.[15]

When is magnetic resonance imaging of the liver needed?

Magnetic resonance imaging is particularly useful when CT has revealed a small or ill-defined liver mass and it is necessary to determine whether it is a metastasis.

MRI better characterizes soft tissue and, in certain situations, allows for a more accurate assessment of small liver lesions. The American Cancer Society notes its usefulness in assessing liver tumors. [16]

Chinese national guidelines for gastric cancer also suggest using MRI if CT scan cannot reliably determine the nature of suspected liver metastasis.[17]

This is especially important with a single small lesion, as a mistake can completely change the stage:

M0 → potentially localized disease

Or

M1 → stage IV.

Is PET-CT necessary?

Positron emission tomography combined with computed tomography is not a mandatory examination for every patient with stomach cancer.

ESMO does not recommend the routine use of FDG-PET-CT for initial staging.[18]

One reason is that some types of gastric cancer poorly accumulate fluorodeoxyglucose, so a negative result does not rule out metastases. The American Cancer Society also notes that PET is less useful for certain histological types of gastric tumors. [19]

However, PET-CT may be used selectively, for example if there remains uncertainty regarding other distant lesions and the result may change the treatment strategy.

Is it necessary to do a biopsy of liver metastases?

Not always.

If a patient has already been morphologically confirmed to have gastric adenocarcinoma, and CT or MRI shows a typical picture of multiple metastases, additional puncture of each lesion is usually not necessary.

A biopsy may be useful if:

• a single atypical lesion was detected;
• there is doubt that this is a metastasis at all;
• another liver tumor is possible;
• it is necessary to obtain additional material for molecular research;
• The result will fundamentally change the treatment strategy.

Computed tomography can be used to guide needle biopsy of a suspicious metastatic lesion.[20]

Therefore, the presence of a formation in the liver on ultrasound or even CT does not always automatically mean metastasis.

What else can a lesion in the liver look like?

In a person with stomach cancer, any new liver growth requires oncological alertness, but not every growth is a metastasis.

Benign changes are also often found in the liver, for example:

• simple cysts;
• hemangiomas;
• areas of fatty infiltration;
• some vascular and hyperplastic formations.

In addition, the development of a primary liver tumor is possible, although this is a separate disease.

This is why a single small, undefined lesion sometimes requires further examination with MRI or, less commonly, biopsy instead of automatically declaring the disease stage IV.

Is it necessary to determine biomarkers for liver metastases?

Yes. This is one of the most important steps in choosing a treatment.

Current guidelines for unresectable or metastatic gastric cancer recommend testing at least:

• HER2;
• PD-L1 with the definition of a combined positive CPS indicator;
• microsatellite instability or DNA mismatch repair deficiency - MSI/MMR;
• Claudin 18.2 - CLDN18.2. [21]

Liver metastases specifically do not require a separate, specialized drug regimen. Treatment is selected based on the characteristics of the entire gastric cancer, its molecular profile, the extent of its spread, and the patient's condition.

This is one of the reasons why a modern diagnosis of "stomach cancer with liver metastases" must contain more information than just the name of the organ to which the tumor has spread.

How are liver metastases treated in stomach cancer?

For most patients, the basis is systemic antitumor therapy, that is, drugs that affect tumor cells throughout the body, and not just the liver.

The NCI lists for stage IV a combination of chemotherapy, targeted therapy, immunotherapy, and palliative local methods. [22]

The choice of first line depends significantly on biomarkers.

Biological variant	What approaches can be considered?
HER2-negative	Fluoropyrimidine + platinum, often with immunotherapy
PD-L1-positive	The combination of chemotherapy with anti-PD-1 is particularly relevant.
MSI-H/dMMR	High sensitivity of many tumors to immunotherapy
CLDN18.2-positive, HER2-negative	Zolbetuximab + chemotherapy
HER2-positive	HER2-directed therapy + chemotherapy, in some cases with immunotherapy
HER2-positive after prior HER2 therapy	Among the next options is trastuzumab deruxtecan

Specific combinations and regulatory indications vary between countries.[23]

Treatment of HER2-negative cancer

The first-line regimen typically consists of a combination of a fluoropyrimidine and a platinum agent, with current guidelines often favoring oxaliplatin over cisplatin, particularly in patients for whom toxicity is a concern.[24]

For many patients, immunotherapy is added.

ESMO recommends nivolumab with chemotherapy for untreated metastatic gastric cancer with PD-L1 CPS of at least 5; the pan-Asian adaptation also allows pembrolizumab with chemotherapy, especially at higher PD-L1 expression. [25]

In the US, pembrolizumab with a fluoropyrimidine and platinum has FDA approval for first-line HER2-negative locally advanced unresectable or metastatic gastric and gastroesophageal junction cancer.[26]

What is CLDN18.2 and why should I check it?

CLDN18.2 is a protein that can persist on the cell surface of certain gastric adenocarcinomas.

If the tumor:

• HER2-negative;
• CLDN18.2-positive,

The targeted drug zolbetuximab in combination with a fluoropyrimidine and platinum may be considered.

The FDA approved this combination in October 2024 for first-line treatment of locally advanced, unresectable or metastatic gastric/esophagogastric junction adenocarcinoma with CLDN18.2-positive disease.[27]

The 2025 Japanese guidelines also include CLDN18.2 among the four key biomarkers that are desirable to be identified before first-line treatment. [28]

How is HER2-positive cancer treated?

HER2-positive metastatic gastric cancer requires a separate strategy.

The traditional first-line regimen is a combination of trastuzumab with a fluoropyrimidine and platinum. ESMO recommends trastuzumab with chemotherapy for HER2-positive tumors. [29]

In the US, for HER2-positive cancer with PD-L1 CPS of at least 1, the FDA granted conventional approval in March 2025 to the combination of pembrolizumab, trastuzumab, and fluoropyrimidine-platinum chemotherapy. [30]

But in August 2026, another important regulatory news appeared.

What's changing in the treatment of HER2-positive metastatic cancer in August 2026?

On August 25, 2026, the FDA approved zanidatamab for first-line treatment of HER2-positive unresectable or metastatic gastroesophageal adenocarcinoma.

Two schemes have been approved:

• zanidatamab + fluoropyrimidine/platinum for HER2 IHC 3+;
• zanidatamab + tislelizumab + fluoropyrimidine/platinum for HER2 IHC 3+ or IHC 2+/ISH+. [31]

In phase III HERIZON-GEA-01, the addition of zanidatamab and tislelizumab improved both progression-free survival and overall survival compared with trastuzumab and chemotherapy: median overall survival was 26.4 versus 19.2 months in the matched study population.[32]

These results apply to the entire HER2-positive metastatic gastroesophageal cancer study group, and not specifically to patients with liver metastases only.

Additionally, this is a US approval. As of early September 2026, the FDA indicated that the application was still under review in Canada and the UK; national indications in other countries may vary. [33]

Why molecular testing should be done before starting the first line

In the past, metastatic gastric cancer was treated primarily using the "chemotherapy for all" principle.

Nowadays, the same diagnosis can lead to completely different patterns:

HER2+ → HER2-directed therapy;

CLDN18.2+ / HER2− → zolbetuximab is possible;

PD-L1 with high CPS → anti-PD-1 therapy is particularly relevant;

MSI-H/dMMR → particularly high probability of clinical benefit from immune checkpoint inhibitors.

The 2025 Japanese guidelines explicitly recommend testing HER2, CLDN18.2, PD-L1, and MSI/MMR before initiating first-line treatment for unresectable or recurrent disease. [34]

Therefore, it is not advisable to begin modern treatment for metastatic gastric cancer without knowing these characteristics if the clinical situation allows waiting for test results.

Is it possible to remove liver metastases surgically?

For most patients, no. For a small, strictly selected group, it can sometimes be discussed.

ESMO formulates its position rather cautiously: resection of metastases cannot be recommended routinely, but can be considered individually in oligometastatic disease and a good response to systemic therapy. [35]

The 2025 Japanese guidelines are somewhat more specific: surgical resection of a solitary liver metastasis is weakly recommended unless there are other incurable factors. The level of evidence remains C. [36]

This means that the situation:

One small metastasis in the liver, no other metastases

Not equal to the situation:

Dozens of metastases in both lobes of the liver + metastases in the peritoneum.

Although both formally belong to stage IV.

What is oligometastatic gastric cancer?

Oligometastatic disease is an intermediate concept between localized tumor and widespread metastatic process.

There is no single, universal definition for gastric cancer. Typically, it refers to a small number of distant lesions, limited to a single organ or anatomical area, and potentially accessible for complete local control. [37]

The most favorable situation for the liver is considered to be:

• single metastasis;
• absence of peritoneal metastases;
• absence of other distant organs;
• the ability to completely remove the primary tumor and metastases;
• good general status;
• good response to systemic therapy.

Even under these conditions, surgery remains a matter of discussion among a multidisciplinary team, rather than an automatic standard.

What liver surgery studies show

In 2024, a systematic review and meta-analysis of 50 studies was published, including 1966 patients who underwent removal of gastric cancer metastases from the liver.

Among these highly selected surgical patients, the five-year overall survival rate was approximately 25%. More favorable results were observed in solitary and metachronous metastases.[38]

But this figure cannot be interpreted as follows:

"With metastases from stomach cancer to the liver, after surgery, 25% of patients will survive for five years."

Why? Because the studies were mostly retrospective, and surgery was initially offered to patients with the most favorable characteristics:

• small metastatic volume;
• absence of other foci;
• possibility of R0 resection;
• good general condition;
• less aggressive biology of the disease.

This selection bias—the selection effect—can greatly inflate the apparent benefits of an operation.

What the RENAISSANCE randomized trial showed

This question is particularly important because for a long time the arguments for surgery in limited stage IV disease were based primarily on retrospective data.

Phase III RENAISSANCE/AIO-FLOT5 compared continuation of systemic therapy with radical surgery of the primary tumor and metastases after initial chemotherapy in patients with limited metastatic gastric or gastroesophageal junction cancer.[39]

In the presented randomized analysis, the study did not meet the primary endpoint of overall survival. The surgical group had an increased early mortality rate, and patients with peritoneal spread and no response to initial therapy did not benefit.[40]

This is a crucial limitation to the idea that "if there are few metastases, it is better to remove everything."

RENAISSANCE data do not support the use of routine surgery in all oligometastatic stage IV disease.

This is why ESMO maintains a very cautious position, and Japanese guidelines limit surgical recommendation in the liver to a virtually ideal situation - solitary metastasis without other incurable factors. [41]

Why do Japanese and European guidelines differ slightly in their results?

Japan has accumulated extensive surgical experience in the treatment of gastric cancer and liver metastases, including long-term retrospective series of carefully selected patients.

Therefore, the Japanese Gastric Cancer Association 2025 allows surgical resection of a single liver metastasis in the absence of other incurable factors - however, the recommendation itself remains weak and has a level of evidence of C. [42]

ESMO formulates the recommendation more broadly and cautiously: metastasectomy is not generally a standard, but can be discussed in very carefully selected patients with oligometastases, especially after response to chemotherapy. [43]

In fact, international positions are not as contradictory as they might seem:

Conventional multiple metastatic cancer → systemic therapy;

Very rare liver-only/solitary disease → discussion of local treatment in a specialized center.

Is it possible to destroy metastases by ablation?

Thermal ablation is the destruction of a tumor site using high or low temperatures without the classic removal of a section of the liver.

Radiofrequency and microwave ablation are used in general liver oncology. The American Cancer Society considers ablation as one of the local treatment options for a small number of liver metastases. [44]

But for metastases from stomach cancer, the evidence base is much weaker than, for example, for colorectal cancer.

Therefore, ablation should not be considered as a standard alternative to systemic therapy.

It may be discussed at a multidisciplinary consultation in selected patients with very limited disease if the anatomy of the metastasis and the patient's condition allow local intervention.

What about radiation therapy for liver metastases?

Stereotactic radiotherapy allows for the delivery of a high dose of radiation to a small, localized area.

In general practice for the treatment of liver metastases, this strategy is used in some patients with a limited number of lesions, especially if surgery is not possible. [45]

However, in gastric cancer it does not replace systemic treatment and is not considered a proven cure for standard metastatic disease.

With multiple metastases, the main problem is not only the visible liver nodes, but the systemic nature of the disease.

Is it worth removing the stomach itself if there are already metastases in the liver?

Routinely - no, if the operation is needed only to reduce the tumor volume.

ESMO does not explicitly recommend gastrectomy for metastatic gastric cancer except when needed to relieve symptoms. [46]

Japanese guidelines also emphasize that so-called reduction surgery—removal of the stomach for incurable metastases solely to reduce tumor mass—should not be performed in a patient who is able to receive systemic chemotherapy.[47]

The basis was, among other things, the randomized REGATTA trial, in which the addition of gastrectomy to chemotherapy did not improve survival compared with chemotherapy alone. [48]

Surgery may still be necessary to control:

• severe bleeding;
• obstruction;
• perforations;
• other local complications.

In this case, the purpose of the operation is primarily palliative.

What is a conversion operation?

Sometimes, initially unresectable cancer responds very well to systemic therapy: metastases shrink or disappear on imaging, and the surgeon begins to consider the possibility of completely removing the residual disease.

This strategy is called conversion surgery.

The 2025 Japanese guidelines acknowledge its potential but highlight the lack of sufficient randomized evidence and do not provide a clear recommendation for all patients with stage IV. [49]

Retrospective studies have indeed shown long-term survival of individual patients after R0 conversion surgery, but here again a strong selection effect is at work: predominantly people with an exceptional response to drugs and favorable tumor biology progress to surgery.

Therefore, the disappearance of a metastasis after chemotherapy on CT does not automatically mean that surgery will now necessarily improve the prognosis.

How is treatment response assessed?

After several cycles of systemic therapy, repeat imaging is usually performed.

Main questions:

• have liver metastases decreased;
• have new outbreaks appeared;
• what happens to the primary tumor;
• have metastases appeared in other organs;
• How is the treatment tolerated?
• Is liver function preserved?
• Have the symptoms changed?

CT remains the primary method for assessing disease spread.[50]

It is especially important to distinguish between:

Reduction of metastasis and complete destruction of all tumor cells.

Even if the lesion is no longer detectable on CT, microscopic tumor tissue may remain.

What is the survival rate for liver metastases?

There is no exact universal figure for metastases of stomach cancer specifically to the liver.

The American SEER statistics include all patients with distant spread of gastric cancer, regardless of whether the metastases are in the liver, lungs, peritoneum, or multiple organs.

For distant gastric cancer, the five-year relative survival rate among patients diagnosed in 2015–2021 is approximately 8%. [51]

This figure cannot be translated as:

"A person with liver metastasis has five years or less to live."

It describes a large historical group of patients with very different diseases.

In addition, the American Cancer Society specifically emphasizes that people starting treatment now may have a more favorable prognosis, since statistics inevitably reflect treatment in previous years. [52]

Why is the prognosis for one and ten metastases completely different?

Formally, both situations are M1 and IV stage.

But their biological and medicinal meanings differ significantly.

More favorable signs in studies of patients with liver metastases were considered:

• single lesion;
• damage to only one lobe of the liver;
• small size of metastasis;
• absence of other distant metastases;
• metachronic appearance;
• possibility of complete R0 resection;
• lower stage of primary tumor;
• good response to systemic therapy. [53]

Stage IV therefore defines a general category of disease, but within it there remains enormous prognostic heterogeneity.

Is it possible to cure stomach cancer with a single liver metastasis?

Sometimes, in exceptionally selected patients, long-term survival without visible disease is achieved, but a guaranteed cure cannot be guaranteed.

A 2024 meta-analysis of surgical series showed approximately 25% five-year overall survival after resection of liver metastases in a highly selected group.[54]

However, these results do not prove that surgery itself was responsible for the better outcome.

The randomized RENAISSANCE did not demonstrate an overall benefit of radical surgery for the entire category of limited metastatic disease.[55]

Therefore, it is more correct to say:

Standard stage IV disease is usually treated with the aim of long-term disease control, and a potentially radical multimodal strategy may only be considered in very rare oligometastatic situations.

What influences the prognosis the most?

For an individual prognosis, it is much more useful to know not only the fact “there are metastases in the liver,” but the entire clinical picture.

The following are important:

The extent of metastatic disease. A single metastasis and multiple bilateral lesions are fundamentally different situations.

The presence of other organs. Liver-only disease has a different local therapy potential than combined liver, peritoneum, and lung therapy.

Response to first-line therapy. A significant reduction in tumor burden after systemic therapy is a favorable sign.

General condition of the patient. Current Japanese guidelines consider systemic chemotherapy primarily in patients with preserved functional status and acceptable organ function. [56]

Biomarkers HER2, PD-L1, MSI/MMR, and CLDN18.2 may provide access to effective targeted or immune therapy. [57]

The possibility of local control. For rare solitary liver metastases, this may be an additional factor.

What to do if a metastasis is detected for the first time

After the phrase “a CT scan revealed a lesion in the liver,” it is useful to move not immediately to the question of surgery, but gradually.

To make sure that the lesion is truly metastatic

If the lesion is solitary or appears atypical, an MRI of the liver and sometimes a biopsy may be required.[58]

Determine the total volume of distribution

It is necessary to evaluate not only the liver, but also the chest, lymph nodes, peritoneum, and other potential sites of metastasis. Contrast-enhanced CT of the chest, abdomen, and pelvis is the basis for this assessment. [59]

Check HER2, PD-L1, MSI/MMR, and CLDN18.2

These results have the potential to completely change the choice of first-line treatment.[60]

Determine the general condition and function of organs

The tactics depend on the physical condition, nutrition, liver and kidney function, concomitant diseases and the ability to tolerate combination treatment.

Initiate appropriate systemic therapy

For most patients, this is the main first step.

Re-evaluate the disease after treatment

If metastases have significantly decreased, the further strategy is discussed again.

In case of a single liver-only metastasis, obtain the opinion of a specialized team

It is advisable to include a medical oncologist, a gastric cancer surgeon, and a hepatobiliary surgeon in this team.

It is this rare situation that potentially lends itself to discussion of resection or another local approach.[61]

What questions should you ask your oncologist?

In the case of liver metastases, it is more useful to get specific answers than to limit yourself to the phrase “stage four”:

1. Is the metastasis definitely confirmed or is an MRI/biopsy needed?
2. How many metastases are there in the liver?
3. Are they in one share or in both?
4. Are there any metastases anywhere else?
5. Are HER2, PD-L1 CPS, MSI/MMR and CLDN18.2 tested?
6. What is the first line of treatment suggested and why?
7. How will the answer be assessed?
8. Is the disease oligometastatic?
9. Is there any point in discussing the case with a hepatobiliary surgeon?
10. If surgery is not indicated now, can the strategy be changed if there is a good response?

These questions help distinguish the common, widespread M1 from the small group of patients for whom a more aggressive multimodal strategy is potentially considered.

When urgent medical care is needed

The mere presence of liver metastases is usually not a reason to call emergency services. However, complications of the disease or treatment may require prompt assistance.

Urgent assessment is needed when:

• severe or rapidly increasing jaundice;
• sudden confusion or unusual drowsiness;
• severe abdominal enlargement with difficulty breathing;
• repeated vomiting and inability to drink;
• significant gastrointestinal bleeding;
• sudden weakness or fainting;
• high temperature during antitumor treatment, especially if neutropenia is possible.

In severe liver damage, the accumulation of toxic products can lead to hepatic encephalopathy with drowsiness, confusion and, in extreme cases, coma. [62]

What is often misunderstood

"Liver metastasis means liver cancer." No. The tumor cells remain the cells of the original stomach cancer; the disease is called metastatic stomach cancer. [63]

"If a stomach tumor touches the liver, it's automatically stage IV." No. Direct T4b invasion into the adjacent liver and a separate M1 metastasis are different categories. [64]

"If there is only one metastasis, it must be removed." No. Japanese guidelines only allow such an operation as a weak recommendation, and ESMO does not recommend metastasectomy routinely. [65]

"If a metastasis disappears on a CT scan after chemotherapy, the cancer is cured." No. A radiological complete response does not guarantee the absence of microscopic tumor cells.

"The stomach must be removed first to prevent the tumor from metastasizing further." Once the asymptomatic metastatic stage has been established, routine gastrectomy to reduce tumor burden has not improved survival and is not the standard. [66]

"Local surgery is pointless at any stage IV." That's also too categorical. For a very small group with a single liver-only metastasis, local treatment can be discussed individually. [67]

Key points from experts

Kohei Shitara is a medical oncologist and Chief, Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Japan. The National Cancer Center of Japan acknowledges his leadership of the Department of Gastrointestinal Oncology and his leading role in international drug therapy research for gastric cancer. [68]

In the pan-Asian adaptation of the ESMO guidelines, first authored by Shitara, metastatic gastric cancer is considered primarily as a systemic disease: biomarker-guided drug regimens are recommended, gastrectomy is not recommended without palliative indications, and removal of metastases is allowed only as an individual option for carefully selected oligometastatic disease.[69]

Masanori Terashima, MD, PhD, FACS, is a gastric surgeon and Deputy Director of Gastric Surgery at Shizuoka Cancer Center, Japan. The center's official profile lists his specialization as gastric cancer surgery. [70]

A 2024 meta-analysis from the Shizuoka Cancer Center group, including Terashima, summarized data from 1966 patients who underwent resection of liver metastases. The authors demonstrated the potential for long-term survival in carefully selected patients, particularly with solitary and metachronous metastases, while highlighting the uncertainty surrounding optimal selection criteria and the role of perioperative therapy. [71]

Salah-Eddin Al-Batran is Professor and Medical Director of the Institute of Clinical Cancer Research, Krankenhaus Nordwest/University Cancer Center Frankfurt, and a specialist in gastrointestinal oncology. His current position is endorsed by UCT Frankfurt and Krankenhaus Nordwest. [72]

The Al-Batran research group conducted the randomized RENAISSANCE trial, which directly tested the idea of radical surgery after chemotherapy for limited metastatic gastric and gastroesophageal junction cancer. The presented results showed no overall survival benefit of the surgical strategy for the entire study population and demonstrated additional early surgical risk, strengthening the arguments against automatic surgery for oligometastases. [73]

Frequently Asked Questions

What stage is liver metastasis in stomach cancer?

Stage IV, if we are talking specifically about a separate distant metastasis - M1. [74]

What if the stomach tumor has simply grown into the liver?

It may be T4bM0 and not necessarily stage IV. Direct invasion of an adjacent organ differs from a separate metastasis. [75]

Can there be only one metastasis?

Yes. Both single and multiple liver metastases are possible. [76]

If there is only one metastasis, can it be removed?

Sometimes. Japanese guidelines weakly recommend resection of a single liver metastasis in the absence of other incurable factors. ESMO suggests considering this approach only on an individual basis in carefully selected patients. [77]

Is it possible to cure stage IV with one operation?

Generally, no. Metastatic cancer is considered a systemic disease, and drug treatment remains the mainstay of treatment. The randomized RENAISSANCE trial did not confirm the benefit of a routine radical surgical approach for the entire limited M1 group. [78]

How are liver metastases treated?

First of all, systemic therapy selected based on HER2, PD-L1, MSI/MMR and CLDN18.2. [79]

Is it necessary to do an MRI of the liver?

Not for everyone. It is especially useful when CT reveals a small or ill-defined lesion whose nature needs to be clarified. [80]

Is a biopsy of every metastasis necessary?

No. It is used selectively if the diagnosis is unclear or the result could change the treatment.

Can a metastasis not hurt?

Yes. Liver metastases often do not cause symptoms in the early stages. [81]

Does jaundice mean there are a lot of metastases?

Not necessarily, but jaundice may occur with significant liver damage or bile flow obstruction and requires evaluation. [82]

What is the five-year survival rate?

For the entire category of distant gastric cancer, US statistics from 2015-2021 indicate a five-year relative survival rate of approximately 8%. This is not a specific indicator for liver-only metastases or a personal prognosis. [83]

Why do they say the five-year survival rate is 25% after surgery for liver metastases?

This is the result of a meta-analysis of very carefully selected surgical patients, not the entire stage IV population. Such figures cannot be directly compared to the general metastatic cancer population or used to predict the outcome of a specific individual. [84]

Which is better - surgery or chemotherapy?

For most patients, systemic therapy is the treatment of choice. Surgery is considered only in rare oligometastatic cases and has no proven benefit for all stages IV. [85]

Should I check HER2 if I already have metastases?

Yes, HER2 directly influences treatment choice, as do PD-L1, MSI/MMR, and CLDN18.2. [86]

Will there be new treatments in 2026?

Yes, on August 25, 2026, the FDA approved zanidatamab with chemotherapy, and the combination of zanidatamab, tislelizumab, and chemotherapy for certain HER2-positive metastatic gastroesophageal adenocarcinomas. Regulatory status in other countries may vary.[87]

Main

Liver metastases from gastric cancer represent distant M1 metastases and stage IV if they are isolated metastatic lesions. This must be distinguished from direct T4b tumor growth into the adjacent liver, which, at M0, may remain stage III. [88]

The mainstay of treatment for most patients is systemic antitumor therapy, the choice of which is now largely determined by HER2, PD-L1, MSI/MMR, and CLDN18.2. In 2026, the first-line spectrum continued to expand: new combinations with zanidatamab became available in the United States for HER2-positive metastatic disease. [89]

Liver surgery is the exception, not the rule. ESMO does not recommend routine removal of metastases, and Japanese guidelines allow resection of a single liver metastasis only as a weak recommendation in the absence of other lesions. The randomized RENAISSANCE trial further demonstrated why the results of retrospective surgical series cannot be used as a universal standard.

For a specific prognosis, it is much more important to know how many metastases there are, whether there is disease outside the liver, how the tumor responds to systemic treatment, what the HER2/PD-L1/MSI/CLDN18.2 levels are, and whether it is possible to completely control the disease locally, than to rely solely on the words “stage four.”