Colorectal (large intestine and rectum),lung, pancreas, breast, neuroendocrine, stomach and esophageal cancers are the most common cancers that spread to the liver.
The incidence of colorectal cancer on its own is 3rd in the world. In addition, since the blood and lymph flow of the large intestine and rectum pass through the liver and then join in the circulation, the risk of settling in the liver which is the first stop on the road will be naturally higher.
Metastases develop in the liver in 50% of patients with colorectal cancer. When colorectal cancer is diagnosed, metastasis can be detected in the liver (synchronous metastasis),or metastasis in the liver can be encountered months after the treatment of colorectal cancer (metachronous metastasis).
While the 5-year survival chance is 3-6% in those who are not treated, this rate increases up to 50% in those who can undergo complete surgical resection. However, recurrence rates of liver metastases after treatment are also high. Within two years, the disease recurs in half of the patients. Early diagnosis of CRC liver metastases is still problematic. When diagnosed, only 15-20% of patients are suitable for surgical resection.
As in the diagnosis of all liver metastases, ultrasound, CT and MRI are auxiliary imaging methods for diagnosis. Ultrasound is an inexpensive and easily accessible examination. CT is important in surgical planning in terms of clarifying the size and number of metastases as well as the relationship between the lesion-vessel and biliary tract. MRI is quite superior to others in detecting small lesions in the fatty liver. PET scanning of the whole body is also valuable to assess the presence of metastases outside the liver.
When CRC and liver metastases are detected at the same time (synchronous metastasis),it is first checked whether the cancer in the large intestine or rectum is bleeding or obstructive. If there is a bleeding and occlusive tumor, priority is given to it due to urgency and surgical treatment is often applied. If there is no bleeding and obstruction, radiological and endoscopic examinations are completed to clearly determine the stage of the cancer in the body. The general health status of the patient is evaluated.
In the multidisciplinary oncology council, chemotherapy, chemo-radiotherapy and surgery options are discussed according to the stage of the cancer and a treatment plan is prepared. In metachronous metastases, it is a common approach to start with chemotherapy first (neoadjuvant chemotherapy) in order to see the biological behavior of cancer cells and their response to chemotherapy. Since those who respond to treatment, that is, those whose tumors shrink, have a high chance of benefiting from surgical treatment, this method is used as a selection criterion and those who respond are continued with surgery.
Direct surgery is recommended for metachronous liver metastasis detected when it is single and smaller than 3 cm. Surgical resection and percutaneous radiofrequency (RF) ablation have similar efficacy in these. However, RF ablation is not suitable for metastases with larger size (>3 cm),adjacent to the main vessels or superficial diaphragmatic location. In these, its effectiveness with RF is controversial.
If the metastasis in the lung can be surgically removed with clean margins, surgical treatment may continue as an option.
In metastatic disease, the liver's own structure is assumed to be normal. Of course, there is a risk that chemotherapy and targeted drugs to be taken will impair the quality of the liver parenchyma, and this should be kept in mind in the calculations. As a result, parenchyma-enhancing methods are used in cases where it is thought that the liver that will be left behind will not be sufficient for the patient in terms of volume and quality.
The aim here is to cut off the blood flow to the diseased part of the liver to be removed, to direct all the blood to the part of the liver that is planned to be left behind and to ensure its growth. 2-stage hepatectomy with portal vein embolization or ligation or ALLPS, which has been applied in recent years, are procedures performed to give a chance to patients with small non-tumor liver volume.
Recurrences of CRC metastases after surgical treatment are quite common. In these, re-surgic re-surgery and removal of metastases (re-resection) can be applied for curative purposes. Resection of extrahepatic recurrences (especially in the lung) can also be performed safely, providing a clear survival benefit. Although there are studies reporting survival benefits with peritonectomy and warm intraperitoneal chemotherapy (HIPEC) in peritoneal metastases of colorectal cancer, the treatment of peritoneal metastases is much more problematic.
In addition to the benefits of preoperative chemotherapy, there are also problems it creates. Prolonged chemotherapy applications cause steatosis (fatty growth) in the liver. It is often seen after 5-FU and irinotecan treatment. In treatments with oxaliplatin, sinusoidal obstruction syndrome may develop. Sinusoidal obstruction does not increase the risk of perioperative mortality, but it increases the risk of complications.
With the introduction of biologic agents, the efficacy of chemotherapy in CRC metastases and its positive effects on long-term survival have increased significantly. These are antibodies to vascular endothelial growth factor (VEGF) and epidermal growth factor receptors. Biological agents are especially effective in patients with unmutated KRAS (wild type) in tumor tissue. Patients using bevacizumab, a VEGF receptor blocker, should stop taking bevacizumab 6 weeks before the scheduled operation date, as side effects such as bleeding tendency and delayed wound healing may occur during surgery.
Transarterial chemoembolization (TAKE) is one of the treatments that can be applied in liver metastases of CRC that cannot be surgically performed. TAKE allows high-dose chemotherapy to be administered into the lesion without the risk of systemic toxicity. Although the early response is higher, overall survival outcomes are similar to those of systemic chemotherapy (median survival: 17 months). Another option is to apply direct radiation to the tumor tissue by arterial infusion of Yttrium microspheres.
This method is a good option, especially for patients who do not benefit from CT. It has been shown that early response is achieved in 50% of tumor nodules with yttrium (median survival: 9 months). Thirdly, external radiotherapy is the implementation.
However, the application of radiotherapy to liver masses has been limited for years due to radiation-induced hepatitis. Today, with technological advances, it has been possible to apply radiotherapy only to tumor tissue with new techniques such as 3D conformal radiation therapy and stereotactic body radiation.
When stereotactic body radiation and intrahepatic chemotherapy were applied together, local control was achieved in 77% of cases, and 2-year survival was reported as 50%. This has shown that radiotherapy can be used as an alternative method in cases where curative treatment is not possible.
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Prof. Dr. Sedat Karademir
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