Diagnosis & Treatment
Liver Cancer

Liver cancer treatment in Germany: diagnosis, therapy and surgery

Liver cancer treatment in Germany: diagnosis, therapy and surgery

Modern methods of liver cancer treatment in Germany provide the best survival rates in Europe, even with advanced stages of the disease.

Liver cancer is a malignant disease in which liver cells begin to multiply uncontrollably and penetrate into other organs and tissues.

The disease is also called "primary" liver cancer, because the tumor originates from the organ itself.

The most common type is hepatocellular carcinoma (HCC).

In contrast, “secondary” liver cancer is a metastasis originating from malignant tumors of other organs (for example, colon cancer or stomach cancer).

Secondary tumors differ in their course and methods of treatment from primary tumors. Further, only primary liver cancer is discussed.

Statistics and prognosis for liver cancer

In the past, this disease was considered relatively rare in Germany. About 8,790 new cases of HCC are registered annually in the country (6,160 men and 2,630 women) – significantly less compared with lung tumors. The average age of onset is 70 years for men and 72 years for women.

In Germany, other European countries and the United States, the incidence is rapidly increasing: the number of new cases has doubled in the last 35 years. This increase is associated with an increase in the number of patients with cirrhosis, as well as with a high incidence of viral hepatitis, the spread of obesity and type 2 diabetes. In men, HCC occurs 2-3 times more often than in women.

About 7 out of 10 cases of HCC are diagnosed in advanced stages. The prognosis in such cases is unfavorable. Currently, all patients with cirrhosis, patients with chronic viral hepatitis or non-alcoholic steatohepatitis (NASH) require periodic examinations.

Thanks to the monitoring of risk groups, the proportion of early liver cancer cases in Germany increased, while the proportion of HCC at a late stage decreased accordingly. Sonographic detection of HCC leads to a significant increase in survival: 5-year survival now exceeds 50%. On the other hand, the benefit resulting from the use of the AFP tumor marker has not been proven.

Where to go for liver cancer treatment?

Today in Germany there are dozens of medical centers that provide world-class cancer care to foreign patients. Among them are major academic hospitals and private clinics, where experienced specialists work in the field of hepatobiliary neoplasms. Here the best technologies and therapies are available, so most medical tourists seek second opinion and therapy in these centers.

We recommend the following clinics that deal with liver tumors at all stages:

• Charite Hospital in Berlin
• Liver Center at Helios Hospital Berlin-Buch
• Center for Liver Surgery at Asklepios Hospital Barmbek 
• University Medical Center Hamburg-Eppendorf
• Nordwest Hospital in Frankfurt

The listed clinics are famous for high quality treatment and excellent performance.

Diagnosis of liver cancer in Germany

Liver cancer rarely causes discomfort at the beginning of its growth. Small, asymptomatic tumors of the liver are often found by chance during routine examinations, but in the near future, German doctors hope to detect them primarily with a targeted sonographic examination. The first non-specific signs of hepatocellular carcinoma usually occur at a late stage of the disease. Unfortunately, at the time of these symptoms it may be too late to achieve full recovery.

Possible symptoms include:

• Loss of appetite and nausea
• Dull pain in the upper abdomen
• Weakness and decreased performance
• Unexplained weight loss
• Fever of unknown origin
• Jaundice and pruritus

If you observe these symptoms, it does not mean that you have a tumor. All these complaints may also be due to relatively harmless causes. Contact your doctor as soon as possible to find out.

German clinics are equipped with the most advanced diagnostic equipment for the detection of tumors of any localization. Even with advanced disease, rapid diagnosis can prolong life and significantly improve the patient’s quality of life. If liver cancer (HCC) is suspected, a series of diagnostic tests can clarify whether this is really a malignant tumor and how far the disease has spread.

The most important stages of the diagnostic process are:

• Anamnesis
• Physical examination
• Liver ultrasound
• Laboratory blood tests: starting $ 300
• Liver MRI (magnetic resonance imaging): $ 1000-1500 for one area
• Tumor biopsy: starting $ 2200
• Histological examination of tissue samples: starting $ 600
• Computed tomography (CT) to detect metastases
• PET / CT scan: starting $ 2400
• Sometimes it is necessary to perform a gastroscopy and colonoscopy.

Consultation with an experienced liver tumor specialist costs $ 400-500 or more. Comprehensive screening for at-risk patients, including an oncologist consultation, costs about $ 2000-3000.

Only when the results of all diagnostic studies are available, the doctor can choose the optimal tactics for further treatment. If you are not satisfied with the therapy offered at home, any patient can get a second opinion of German oncologists, surgeons and radiologists within a few days.

Liver cancer treatment in Germany: methods and prices

After a diagnosis of liver cancer has been established and the type of tumor and the extent of the spread of the cancer are determined, the doctor agrees with the patient on further treatment.

Treatment methods available in German clinics:

• Surgery (partial liver removal)
• Liver transplantation: starting $ 120,000
• Percutaneous injection of ethanol or acetic acid (PEI)
• Radio frequency ablation (RFA, RFTA): $ 15,000
• Microwave ablation (MWA) and irreversible electroporation (IRE)
• Ablation using high intensity focused ultrasound (HIFU)
• Transarterial chemical embolization (TACE): starting $ 40,000
• Selective internal radiation therapy (SIRT) or radioembolization: $ 23,000-35,000
• External radiation therapy, brachytherapy, and innovative proton therapy (PT)
• Drug treatment with sorafenib, regorafenib or lenvatinib
• Immunotherapy with PD1 / PD-L1 inhibitors
• Cytotoxic chemotherapy: starting $ 3500 per course

Which therapy is used in a particular case depends on the stage of the disease at the time of diagnosis and the condition of the liver.

The patient's age and chronic diseases are also taken into account when choosing a treatment.

The most important surgical procedures for the treatment of liver cancer are removal of a part of the liver or removal of the entire organ, followed by liver transplantation. However, transplantation is possible in less than 5% of patients. The purpose of the surgery is to completely remove the tumor. However, surgery is considered only in cases where the tumor is limited to the liver. In addition, a good liver function and a number of other conditions are required in order for the patient to benefit from the surgery. In more than three-quarters of cases, a tumor cannot be surgically removed at the time of diagnosis. Alternatively, as well as a stage before liver transplantation, local tumor-destroying (local ablative) treatments are used. These are radio frequency ablation (RFA) and microwave ablation (MWA).

Radiofrequency ablation is equivalent to surgical resection in terms of life extension for small liver tumors (up to 3.0 cm in diameter). In principle, this method can completely cure the disease. If liver tumor cannot be surgically removed or completely destroyed by ablation, transarterial (chemo- or radio-) embolization and / or drug therapy are used.

Treatment with the multikinase inhibitors sorafenib (first-line) and regorafenib (second-line) is useful, but it cannot cure advanced liver cancer. Sorafenib and regorafenib can slow tumor growth for a period of time, relieving tumor-related symptoms.

Local ablative treatments

Radiofrequency ablation

Radiofrequency ablation (radiofrequency thermotherapy) requires the insertion of a probe into a tumor under the control of an ultrasound or CT scan. Radiofrequency waves heat tumor tissue to 100 ° C or more. With this method, liver tumors with a diameter of 4-5 cm can be completely destroyed. If there are several tumors, more than one session is performed under anesthesia. The procedure can be repeated many times.

Currently, RFA has almost completely replaced obsolete and less efficient injections of ethanol and acetic acid. This method of treatment is available in all major clinics in Germany.

Microwave ablation and irreversible electroporation

Microwave ablation (MWA) and irreversible electroporation (IRE) have become reliable and well-studied methods for treating inoperable liver tumors. Compared to RFA, microwave ablation can provide even higher temperatures up to 160 ° C. Therefore, tumors that are located near large and well perfused vessels (eg, portal vein) are preferably treated with microwave ablation.

Irreversible electroporation is a novel, minimally invasive technique for the targeted destruction of cells by strong, localized electric fields. Experience suggests that in contrast to other local treatment methods, IRE specifically destroys tumor cells. Other structures such as blood vessels are not permanently damaged.

Liver cancer treatment in Germany: methods and prices

Due to its technical complexity and limited clinical experience, the use of the IRE is limited to a few centers including University Hospital Regensburg.

Ablation using high intensity focused ultrasound

High-intensity focused ultrasound (HIFU) is a new safe and effective treatment for small liver tumors (less than 2-3 cm). HIFU can prolong life, but this method does not cure cancer completely. Ultrasound ablation is generally well tolerated by patients with cirrhosis.

The choice between HIFU and radiofrequency ablation is based on a variety of factors. Currently, the use of HIFU is limited to several medical centers. The use of local ablative procedures does not exclude the possibility of a subsequent operation. Sometimes these procedures even shorten the time of a liver transplant.

Local ablative procedures are increasingly used in combination with transarterial chemoembolization (TACE). In particular, in liver tumors with a diameter of 3-5 cm, the neoplasm is first reduced by chemoembolization, and then finally destroyed by RFA.

German doctors call such combined treatment approaches "multimodal therapy."

Transarterial embolization (TAE / TACE)

Transarterial chemoembolization (TACE) is a method that combines the principles of embolization and chemotherapy. An interventional radiologist performs local anesthesia, then inserts a catheter through the femoral artery, reaching the hepatic artery. Each tumor is supplied with blood through one or more of smaller blood vessels.

During embolization, small plastic particles are introduced through the catheter into the vessel supplying the tumor, until the vessel is clogged and the blood supply to the tumor stops. Since essential nutrients and oxygen are missing, tumor cells in this area die. This is embolization.

If a chemotherapeutic agent is inserted through the catheter and placed directly into the tumor, this is called chemoembolization. A chemotherapeutic agent (cytostatic) causes death of tumor cells.

Currently, transarterial embolization (TAE) and chemoembolization (TACE) are considered equivalent in terms of their effectiveness. These methods are widely used in Germany.

In early liver cancer, chemoembolization is usually not recommended; Promising local ablative procedures and surgeries are used here. Chemoembolization can delay tumor growth and prolong life. However, treatment should be prescribed only to patients with sufficient liver function. Chemoembolization is also increasingly used in recent years as a step before liver transplantation.

Transarterial chemoembolization (TACE) is often combined with drug therapy (sorafenib) or with other local ablative procedures (for example, radiofrequency ablation).

The recently reported results of the TACTICS study showed for the first time that long-term sequential TACE therapy can be successfully combined with sorafenib, significantly increasing survival. The concepts of multimodal therapy, combining local and systemic approaches, are now increasingly being investigated and applied by German clinics.

The role of "drug-eluting beads (DEB)" (usually loaded with doxorubicin, DC Bead) has not been sufficiently clarified.

The present and published studies showed no superiority over embolization alone (without chemotherapy).

Selective Internal Radiotherapy (SIRT)

For patients with liver cancer without metastases who are not candidates for surgery or ablative therapy, the new method shows promising results. This is transarterial radioembolization (TARE), also called selective internal radiation therapy (SIRT). Selective internal radiation therapy is a type of radiation therapy acting on a liver tumor from the inside. In this method, small granules containing a radioactive substance are injected directly into the blood vessels of the tumor.

For this, 90-yttrium encapsulated into the microsphere (the so-called β-emitter) is inserted through the catheter into the hepatic artery or its small branches. Then the blood vessels of the tumor are sealed, due to which the cancer cells are exposed to a high dose of radiation.

The precise placement of the microspheres in the hepatic artery or its branches is crucial, since the outflow of radioactive microspheres into other blood vessels can lead to significant side effects.

In recent years, SIRT has acquired great importance in the treatment of non-metastatic and inoperable liver cancer. The advantage of SIRT compared with transarterial chemoembolization is that the method is sufficient to use once. As a rule, it does not require a long hospital stay.

External radiation therapy and proton therapy

For large tumors that cannot be removed either surgically or using minimally invasive ablative procedures, external radiation therapy (3D-conformal or stereotactic radiation therapy) is used. Treatment is characterized by a high frequency of clinical response; Currently radiation therapy for liver cancer in Germany is being used as part of research, including combinations with SIRT.

A recently published Phase III study has shown that doxorubicin is undesirable in systemic liver cancer treatment in Germany

With proton therapy, tumors can be controlled more effectively than with conventional radiation. However, to date, there have been no adequate controlled studies on the use of this method in HCC.

Small pilot studies show encouraging results and demonstrate the effectiveness of this approach.

The biggest problem is the cost of proton therapy for foreign patients, which can be hundreds of thousands of dollars. This method is available only in a few high-tech proton therapy centers.

Immunotherapy with PD1 / PD-L1 inhibitors

Immunotherapy using innovative drugs, including the so-called checkpoint inhibitors, is one of the most promising areas of German oncology.

For example, the PD-1 inhibitor nivoluumab in HCC shows a good safety profile even in patients with active viral hepatitis B and C. In the phase I / II studies published to date, a sustained clinical response was observed at all doses. Survival rates after 12 months reached 62%.

Nivolumab is currently being tested with sorafenib as part of the phase III NCT02576509 study, the results of which are expected in 2019. Unfortunately, it has not yet been established immunohistochemical or laboratory markers that could reliably predict the response to nivolumab. The possibility of such a prediction would be valuable, given the high cost of immunotherapy.

In addition to nivolumab, novel PD1 / PD-L1 inhibitors (control point inhibitors) and various antibodies (CTLA-4) are being actively studied in patients with HCC in phase I / II studies.

Chemotherapy of liver cancer

In this developed country, chemotherapy does not play an important role in the treatment of liver cancer in patients with cirrhosis (Child-Pugh B or C). However, in Asia and Africa, many patients with chronic viral hepatitis B develop hepatocellular carcinoma without cirrhosis.

For these patients, doctors offer different chemotherapy regimens, including cisplatin + gemcitabine, cisplatin + interferon + doxorubicin + 5-fluorouracil, doxorubicin + cisplatin, as well as doxorubicin monotherapy, capecitabine monotherapy and 5-fluorouracil + oxaliplatin. The combination of 5-fluorouracil (5-FU) and oxaliplatin has already acquired some clinical status in Asian countries. In Hong Kong and China, the FOLFOX4 and SECOX (sorafenib, oxaliplatin, capecitabine) regimens are mainly used for advanced hepatocellular carcinoma.

In Germany and other Western countries, there is still no evidence that the addition of a cytostatic drug (such as doxorubicin) leads to a further improvement in survival achieved with sorafenib. The combination of sorafenib and doxorubicin causes an increase in side effects and toxicity.

A recently published Phase III study has shown that doxorubicin is undesirable in systemic liver cancer treatment in Germany. In general, this confirms the opinion of leading European experts that cytotoxic chemotherapy should not be used in HCC patients.

In patients with good liver function who have had to stop sorafenib therapy due to side effects and who are not candidates for second-line regorafenib therapy, conventional chemotherapy may be appropriate in some cases (German S3 clinical guidelines).

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