Liver Metastases (Liver Secondary)

Liver metastases (LM) mean spread of tumor from other organs via blood stream to the liver. Liver tumor in such cases is called ‘secondary’ with ‘primary’ tumor being the source from which it has metastasized. Surgical procedure (resection) through which such tumors is removed is called metastatectomy (resection of LM) or partial hepatectomy (resection of part of liver).
In traditional cancer staging systems presence of liver metastases is classified as stage IV disease. However with advancements in surgical techniques, perioperative care and chemotherapy options excellent long survival is possible in patients with LM from following primary tumors:

1.   Cancers of the large intestine (Cancers of colon and rectum)
2.   Gastrointestinal stromal tumors (GIST) of digestive tract
3.   Neuroendocrine tumors (NET) of digestive tract
4.   Soft tissue sarcoma (STS)
5.   Breast cancers

In comparison to other tumors, colorectal LMs (CLM) are common. In the following sections, an overview of management of CLM is presented. In view of general similarities for investigations and surgery, only salient features for other LMs are provided.

1.  Management of Colorectal Liver Metastasis (CLM)

Colorectal cancer (CRC) is the third most common cancer worldwide. In India colorectal cancer ranks amongst top 10 most common cancers. Approximately 30% of CRC patients are likely to develop CLM during the course of their disease.

Liver metastases may be diagnosed either at the time of investigative work up for primary cancer (synchronous) or they may develop late and are diagnosed at investigations during follow up (metachronous).


Currently surgical removal (i.e. resection/ metastectomy/ hepatectomy) is the preferred treatment option in view of its potential of long-term survival and chance of cure.

When resection is not technically feasible due to advanced disease, other modalities may utilized to either reduce (‘shrink’) the size of CLM (e.g. chemotherapy for downstaging of liver metastases), or induce liver hypertrophy of the likely liver remnant (portal vein embolization) and local ablative therapies (radiofrequency ablation) for multiple small LM.

All modalities are aimed at making safe liver resection feasible.

A tumor-free margin of1-cm is desirable for resection of CLM. However, several recent studies have demonstrated that R0 resection with ≥1 mm margin is also adequate particularly when the tumor is close to major blood vessels. Deeply situated or large or multiple CLM frequently require removal of large volume of liver. Liver resection is deemed technically safe as long as 2 contiguous segments of adequate volume (1% of total body weight) with intact biliary drainage and vascular inflow / outflow can be preserved in an otherwise healthy liver (i.e. not significantly affected by cirrhosis or fatty liver or previous chemotherapy).

Proper patient selection is the most important step for reduction of postoperative complications. The important aspects of preoperative workup of patients for major liver resection include:

1.   Assessment of fitness for major surgery
2.   Rule out extrahepatic disease i.e. metastatic tumor in other sites. High resolution CT scan of the chest may be performed to rule out lungs metastasis. A whole body PET-CT scan may also be performed to rule out tumor spread to other organs such as brain. However, PET CT scan is not a substitute for good quality CT of the abdomen.
3.   Assessment of feasibility of margin negative resection for CLM. A triple phase CT scan of the abdomen & pelvis is essential for this purpose.
4.   Assessment of liver function for major resection

a.   Functional status of the liver: Child – Pugh classification is a simple and reliable for this purpose.
b.   Future liver remnant volume (FLRV): Assessed at CT volumetry

In present era, novel surgical strategies such as staged hepatectomy or multiple parenchymal resections combined with local ablative therapies e.g. radiofrequency ablation have been successfully used to treat patients with multiple lesions / bilobar disease.

In patients where R0 resection appears doubtful or prognostic criteria are not favourable then neoadjuvant chemotherapy should be considered.

One of the three different surgical approaches in combination with chemotherapy may be applicable in this setting:

– Colorectal cancer (CRC) surgery followed by liver resection
– Liver first approach (resection of liver metastasis followed by resection of primary of CRC)
– Single stage surgery includes simultaneous CRC & liver resection

The decision regarding sequence of surgery should be individualized and is best determined by multi-disciplinary team.

In select patients with limited extrahepatic disease surgery is feasible and is associated with improved survival. Lung metastasis along with CLM has more favourable prognosis in comparison to peritoneal, periportal or paraaortic nodal metastasis.

Last two decades have witnessed many significant advances in surgical techniques and chemotherapy for colorectal cancers. Owing to these advancements CLM patients in whom surgery is feasible, have 5-year & 10-year survival rate of up to 40% & 25% respectively.

2.  Management of liver metastases in Gastrointestinal stromal tumor (GIST)

Primary GIST metastasizes to liver in up to 15% of patients. The primary treatment for GIST liver metastases is combination of tyrosine kinase inhibitor (TKI) and surgical resection. Metastatectomy should be considered for patients on TKI who have responsive or stable disease. Surgery may also be beneficial in selected patients with unifocal progressive disease.

3.  Management of Neuroendocrine Liver metastases (NELM)

In patients with resectable NELM surgical resection should be the preferred treatment. In these patients’ anatomic liver resection is preferred over metastatectomy because of lower incidence of recurrence.

For unresectable NELM – liver transplant may be the optimal treatment in select patients.

Unresectable NELM of midgut & pancreatic origin – palliative resection of primary tumor only is associated with improved overall survival.

More aggressive approach for unresectable NELM of pancreatic origin may be considered patients with better performance status, less advanced disease & tumors located in body / tail of pancreas.

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4.  Management of liver metastases in Soft Tissue Sarcoma (STS)

Because of ineffective chemotherapy for liver metastases in STS, all patients with resectable liver metastases should be considered for surgery.

Liver metastatectomy is associated with 5-year survival rates of > 40 % patients. The factors associated with favourable prognosis include:

– Complete resection (R0)
– Longer disease-free interval
– No tumor recurrence before liver resection
– Repeat resection for recurrent liver metastases

5.  Management of liver metastases in breast cancer

Approximately 10% of breast cancer patients present with liver metastases that are technically resectable. In this carefully selected group of patients prolonged survival is feasible after surgery for liver metastases with 5-year survival rates reaching up to 40% (similar to CLM).