Management of liver metastases from colorectal cancer
What is it?
The liver is often the site of metastases of primary tumors of the digestive system but in fact it can be affected by the localization of any type of tumor due to the significant amount of blood that passes through it, and the function it performs – filtration. Surgical removal of secondary liver tumors (metastases) may be appropriate to increase survival in cases of primary colorectal cancer or neuroendocrine cancer metastases. In other secondary tumors, liver resection does not significantly affect the patient’s survival, and, therefore, is not recommended in principle, although with some exceptions that can be evaluated on a case-by-case basis (for instance, kidney, breast, ovarian, stomach cancer, melanoma). And at the same time, different pharmacological treatment programs (chemotherapy) are needed, depending on the nature and location of the primary tumor.
The liver is the most common site of metastases in colorectal cancer, and in most cases, liver damage determines the duration and quality of life of the patient. Approximately 50% of patients with colorectal cancer develop or will develop liver metastases during the course of the disease (15-20% of patients have liver metastases at diagnosis, while in the remaining cases, liver metastases occur at different periods of clinical development of the disease). That is why this is a very common problem. Significant advance in surgery and pharmacology, as well as advances in knowledge about the disease, have made metastatic liver cancer more treatable, to the extent that approximately one in three patients with liver metastases in colorectal cancer can undergo treatment to cure the disease, which is very likely not to return in the next ten years.
Currently, surgical resection is the primary treatment method for patients with metastases in colorectal cancer. No alternative methods of treatment, both local (radiofrequency thermal ablation, alcoholization) and general (chemotherapy), have yet yielded similar results equal to surgical intervention. In fact, the 5-year survival rate after surgery in patients who have undergone liver resection due to the presence of metastases in colorectal cancer ranges from 16% to 49%. This is a percentage that represents encouraging results compared to the survival rate of untreated patients (0-3%). Surgical resection also provides significant and long-term survival (17-33% after 10 years). And finally, it should be noted that, although the rate of recovery of liver metastases after resection is quite high (40%), further removal surgery still has a significant advantage for survival (30% after 5 years) and, therefore, should be taken into account.
The chances of success of resection surgery in the case of colorectal metastases vary depending on various factors, some of which are related to the primary tumor (biological aggression, the stage of the tumor at the time of diagnosis), others are related to the metastases themselves (number, size, distribution in the liver). Various factors that affect patient survival after surgical removal of colorectal cancer can be combined to create risk estimates for long-term recurrence of the disease. The most famous are estimates of the Sloan-Kettering Memorial Cancer Center in New York (Fong score), the France score (Nordlinger score), and the Japan score (Makuuchi score).
It is always useful to remember that the diagnosis and treatment of a patient with liver metastases from colorectal cancer requires a multidisciplinary approach with the synergistic intervention of surgeons, radiologists, oncologists and radiotherapists: the choice of treatment (surgery, chemotherapy) should be approved by various specialists from the team and the patient in order to optimize the course of treatment and get good results in the short and long term.
Which are the symptoms?
In many cases, liver metastases remain asymptomatic for a long time and cannot be detected by simple palpation until they reach a significant size. However, over time, the presence of metastases can disrupt liver function and cause symptoms such as subfebrile fever, a feeling of heaviness in the upper abdomen, pain in the right side, fatigue, loss of weight and appetite, nausea, jaundice, confusion, etc. Currently, there are no effective preventive measures (other than chemotherapy) to prevent the tumor from metastasizing to the liver. Therefore, the best prevention is the early detection of primary cancer and regular check-ups for timely detection of relapses. Moreover, since liver metastases can develop months or years after the primary tumor is diagnosed, liver tests are common for many types of cancer (primarily colorectal cancer) even after treatment is discontinued.
How is it diagnosed?
In the case of signs and symptoms that may indicate liver metastases (previous cancer with a tendency to liver metastases, weight and appetite loss, nausea, abdominal pain, jaundice), the doctor will prescribe blood tests to assess liver function and the level of certain cancer markers, such as CEA and CA-19-9, which increase, for instance, in the case of colorectal metastases, even after the removal of the primary tumor. However, to better characterize any liver metastases, diagnostic imaging studies are needed: ultrasound, magnetic resonance imaging, computed tomography (CT), positron emission tomography (PET), which make it possible to understand exactly the number of metastases, how extensive they are and where they are located. A biopsy, i.e., taking liver tissue cells to be analyzed under a microscope, is performed only if there are still doubts after the above tests.
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How is it treated?
As mentioned earlier, surgery is the most optimal solution and the only method of treatment (the gold standard of treatment). The possibility of surgical intervention significantly depends on the coexistence of two conditions: the complete elimination of the disease and the preservation of a sufficient amount of the liver to maintain vital activity in the postoperative period. In fact, it should be remembered that the liver has the ability to recover, returning to its original size and function after surgery, but this process takes several months. The risk of liver failure after surgical resection is considered low if at least 40% of the liver is preserved, moderate for residual liver amounts from 40% to 25%, high for volumes less than 25%. In cases where the two conditions mentioned above do not co-exist, surgical excision may be reviewed by applying certain strategies to reduce the volume of metastases before surgery (neoadjuvant chemotherapy) or to increase the volume of the liver to be preserved (preoperative portoembolization). It is also possible to schedule the removal of all metastases with two operations 1-2 months apart (“two-step hepatectomy”) to allow the liver to regenerate between the first operation and the next one, or after a shorter period of time using a new procedure suitable in very select cases called ALPPS (Associating Liver Partitioning and Portal Vein Ligation for Staged Hepatectomy).
As a rule, the operation consists in removing the tumor focus and the surrounding part of the liver so that at least 1 cm of healthy tissue remains between the edge of the tumor and the liver cross-section line, although in certain conditions it is permissible to leave a less thick edge of healthy tissue if this makes it possible to completely remove the tumor while maintaining a sufficient amount of liver.
In patients with liver metastases that are synchronous with colorectal cancer (that is, when metastases are diagnosed simultaneously with primary cancer, during interim tests), the nodules can be removed during colon cancer surgery: thus, the patient undergoes only one operation and is hospitalized once. In addition, in some cases of synchronous metastases, in which it is impossible to intervene directly on both fronts and where the degree of liver disease can significantly affect the patient’s prognosis, liver metastases can be removed before the primary tumor is removed (the “liver first” technique).
Although traditional surgical resection is recommended for patients with metastases exclusively in the liver, recent studies offer promising predictions in the near future for patients with metastases in the liver and extrahepatic abdominal areas (lymph nodes, peritoneum, adrenal glands) or extraabdominal (lungs), provided that all areas of the tumor are removed during the operation.
However, the percentage of patients amenable to surgical treatment at the time of diagnosis is not more than 20-30% of cases; the number of metastases and / or their location in the liver (infiltration of large blood vessels) and / or the degree of replacement of a healthy liver with a tumor often exclude the possibility of surgical resection. In these cases, the appropriate treatment is chemotherapy.
The recent development of more effective chemotherapeutic medicines, such as oxaliplatin and irinotecan, has made it possible to achieve important results in the field of oncology, and in fact has led to a significant reduction in tumor mass and an increase in the survival rate in patients with inoperable metastases, and thus has led to the appearance of 10-20% of initially inoperable patients in addition to those already suitable for surgery.
Systematic chemotherapy is often offered to patients with metastatic colorectal cancer (including candidates for surgery, with some exceptions), before (neoadjuvant chemotherapy) and / or after (adjuvant chemotherapy) liver surgery precisely because it makes it possible to consolidate the long-term results of the operation.
Drugs are usually injected into a vein (intravenously) for distribution throughout the body (systemic chemotherapy). However, if metastases are found only in liver, the possibility of administration directly to the liver (regional chemotherapy) through an arterial blood vessel (intra-arterial chemotherapy) may also be considered. In fact, this method can be used to inject drugs into the liver that are very effective in metastases and that, although highly toxic to the body, are administered in very high doses without much side effects, since the medication is destroyed by the liver itself before it spreads throughout the body.
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