Kidney cancer treatment in Germany: diagnosis, therapy and surgery

Every year, hundreds of medical tourists seek kidney cancer treatment in Germany in order to receive quality and affordable care.

According to the Robert Koch Institute, approximately 16,500 patients develop kidney cancer in Germany each year.

This relatively rare tumor accounts for about three percent of all solid malignant neoplasms; young people are rarely affected.

As a rule, only one of the two kidneys is affected.

Therefore, most patients have no urinary excretion problems for a long time thanks to their healthy second kidney. In 1,5% of all cases, usually in patients with strong genetic predisposition, cancer affects both kidneys.

Malignant tumors of the kidney originate from different tissues.

The most common type is so-called renal cell carcinoma (also known as adenocarcinoma). They make up around 95% of all cases and usually grow from the renal tubule epithelial cells.

About 4% of neoplasms account for a special form – oncocytoma, which appears to be a carcinoma but does not metastasize. Much rarer are tumors of the renal pelvis. They resemble the bladder and ureteral malignant tumors in their tissue structure and therefore treated differently than renal cell carcinoma (RCC). In addition, there are malignant tumors that do not originate from the kidney itself, such as lymphomas (cancer of the lymphatic tissue) and sarcomas that develop in the muscles.

They are extremely rare in adults, as well as nephroblastoma, also known as Wilms' tumor. This is a malignant neoplasm that occurs almost exclusively in children under the age of five. Below we discuss only renal cell carcinoma.

Best clinics for kidney cancer treatment in Germany

The biggest success in the diagnosis and treatment of kidney cancer has been achieved by several large university hospitals, such as the University Hospital Charité in Berlin. There are also several famous private providers that we recommend to medical tourists.

• Universitätsklinikum Essen
• Charité Universitätsmedizin Berlin
• Nordwest Krankenhaus Frankfurt
• Universitätsklinikum Düsseldorf
• Universitätsklinikum Aachen
• Asklepios Klinik Barmbek
• HELIOS Klinikum Berlin-Buch

Some hospitals use experimental procedures and technologies that are not offered anywhere else in the world. Here in Germany, you can find good medical facilities even in small towns. Treatment options, comfort and prices vary greatly, but in general, local clinics compete with each other and try to offer their patients unprecedented quality.

We recommend you contacting only leading certified centers where all the necessary diagnostic and therapeutic instruments are available.

Modern kidney cancer treatment options

Once the diagnosis has been established and the type of tumor has been determined, your doctor will discuss which treatment steps are necessary.

First, the cancer is limited to the kidney. However, as the tumor grows, it can spread through the surrounding connective tissue and occupy nearby tissues, lymph nodes, or nearby organs. Using the bloodstream and lymphatic system, cancer cells can reach distant organs, forming metastases. There they can settle and multiply again Tumor metabolites can then be detected in the patient's blood and urine. At this stage, a complete cure is impossible. Kidney cancer metastases are most common in in the lungs, skeletal system and lymph nodes, more rarely in the brain and liver.

Treatments that may be considered:

• Active surveillance
• Organ-sparing surgery
• Radical surgery (nephrectomy)
• Targeted drug therapy and immunotherapy
• Chemotherapy (in combinations)
• Radiotherapy for metastases
• Palliative care

Treatment choice depends on how advanced the disease is at the time of diagnosis. But the patient's age and overall health are also taken into account when choosing cancer therapy.

The most important treatment option is surgery.

First of all, the procedure is aimed at complete removal of the tumor. This is so called curative surgery, which is only possible when the cancer is limited to the organ. If the tumor has already affected surrounding tissue and lymph nodes or even formed secondary tumors in other organs, surgery is only useful in combination with other methods. In these cases, targeted therapy is actively used. Whether these drugs can really cure kidney cancer completely is still questionable; but usually its growth is slowed down or stopped.

Active surveillance

In elderly patients with comorbidities surgical treatment is not always considered necessary. Often the risk of serious damage from the procedures is greater than the risk of developing metastases or even dying from cancer. As a rule, RCC grows very slowly in old age and do not tend to metastasize; exceptions are possible. When deciding for or against surgery, the biopsy results may be helpful.

In benign tumors (10-20% of the cases) surgery is completely unnecessary. However, if malignant cells are detected during biopsy, your doctor may suggest a different tactic.

Surgical treatment

The treatment of choice in renal cell carcinoma is surgery. The goal of the operation depends on the stage of the cancer. Depending on the size of the neoplasm and its location, attempts will always be made to preserve the affected kidney.

Organ-sparing surgery (cost from $14,000)

It is well known that the organ-sparing surgery (the removal of the tumor leaving the remaining kidney tissue), even with healthy kidney the other side brings significant clinical benefits for the patient. For example, these patients rarely die of heart disease. According to the latest German studies, the risk of cancer recurrence is not higher than after radical surgery (the removal of the entire kidney). Localized small tumors up to 4 centimeters in diameter can usually be removed in this way. An organ-sparing surgery is mandatory if the patient has only one kidney or the second one is not working properly.

It is performed laparoscopically, using tiny incisions on the abdomen (with or without robot-assisted technique). Despite the relative safety, these procedures can lead to complications, especially when tumor is located in the middle of the kidney.

Surgical experience is the main factor for the success of such treatment, regardless of the approach (open surgery or laparoscopic surgery, robot-assisted procedure). If the tumor can be completely removed at the early stage and the kidney function is normal, no further treatment is required. No additional chemo or radiation.

Removal of the kidney (cost from $20,000)

In larger tumors, removal of the affected kidney together with the surrounding fat capsule (radical nephrectomy) is still necessary. It is performed laparoscopically or through a large incision on abdominal wall (open surgery). The current standard in German clinics is a laparoscopic nephrectomy.

During radical surgery, nearby lymph nodes are also removed (hilar or regional lymphadenectomy). This is necessary to accurately determine the spread of the disease. If the tumor tissue could be completely removed, no further treatment is necessary. If the cancer was diagnosed early (single tumor smaller than 7 cm, without lymph node involvement or metastases), then the chances of complete recovery are relatively good.

A significant percent of patients survive long-term after nephrectomy and can be considered cured. The remaining kidney usually copes with its functions for many years.

Ablative therapy

For older people and patients with pre-existing conditions surgery can be very stressful. Therefore, it is possible to treat small tumors up to 4 cm also with local treatment methods. Some German hospitals treat them with cold (cryoablation) or with heat (radiofrequency ablation, RFA). Before starting the ablative therapy a biopsy is made in any case. This will ensure that it is really malignant disease that needs to be treated. Benign tumors or cysts usually require no treatment.

Radiofrequency ablation destroys the tumor by heating to 60-100°C. During the procedure, a probe is inserted directly into the affected tissue. High frequency alternating current generated in the probe ensures a very high temperature in the tissue. Thanks to the special design and modern material of the probe procedure is completely safe for the surrounding tissue.

Cryoablation works on the same principle as radiofrequency ablation. But instead of a probe with alternating current, a freezing probe is placed into the kidney. The tissue is then cooled to about -70°C, which is quickly destroys the malignant cells around the probe.

Treatment of metastatic renal cell carcinoma

According to hospital statistics, 10% of patients already have lymph node and / or organ metastases at the time of diagnosis. In these cases, surgical removal of the tumor-bearing kidney alone can no longer completely cure the disease. Surgery is usually recommended to relatively healthy patients, who will be able to follow up on further treatment to improve outcomes. In addition, kidney removal helps alleviate or prevent cancer-related symptoms and complications such as bleeding and pain.

Surgery can be useful even if only one other organ system is affected by metastases, for example the lungs. Otherwise, conservative management is recommended.

Targeted therapy (cost from $4,000)

The introduction of so-called targeted drugs, which intervene in different signaling pathways of the tumor metabolism and therefore specifically target malignant tissue, is considered a major advance in the treatment of locally advanced or metastatic kidney cancer. Growth factors such as vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) play a key role in the development of renal cell carcinoma. They promote growth of blood and lymph vessels, which supply the tumor with oxygen and nutrients, thereby enabling further cancer progression.



In addition, the growth factors ensure the connection of the tumor to the bloodstream and thus its spread to distant organs. Selective suppression of growth factors by targeted therapies may stop further tumor development.

Since these agents primarily damage the tumor cells and spare healthy organs, they are generally well tolerated. Nevertheless, physicians know about specific side effects of these drugs, which can be very stressful in some cases.

These are some targeted drugs approved for kidney cancer treatment in Germany:

Sunitinib

The multikinase inhibitor sunitinib is approved for the initial treatment of locally advanced and / or metastatic renal cell carcinoma. The decision was based on the results of clinical trial involving a large number of patients, where this drug was able to delay the disease progression much longer than the immunotherapy with interferon-alpha.

Sorafenib

Another multikinase inhibitor sorafenib is approved in Germany for the treatment of patients with advanced renal cell carcinoma if treatment with sunitinib, pazopanib or bevacizumab plus interferon-alpha was unsuccessful. It is used in "second-line therapy", i.e., after failure of previous treatment or as "first-line therapy" in certain groups of patients.

Pazopanib

Like sunitinib and sorafenib, this tyrosine kinase inhibitor is also orally administered. Indications of pazopanib include first-line therapy in patients at low or intermediate risk.

Axitinib

Axitinib can also be taken in tablet form. It is the recently approved targeted agent against renal cell carcinoma and can be used if there has been a failure of previous therapy with sunitinib. Therefore, it is a drug for second-line therapy.

Temsirolimus

mTOR inhibitor temsirolimus is another targeted drug that has been shown to be effective against advanced kidney cancer.

It is approved for first-line treatment of advanced RCC in patients with poor prognosis. Temsirolimus is given intravenously (IV); antihistamine pretreatment is sometimes recommended.

Everolimus

mTOR inhibitor everolimus is administered orally and has been approved for second-line therapy following treatment with tyrosine kinase inhibitors. Sometimes cancers develop resistance to tyrosine kinase inhibitors by creating new signaling pathways or infiltrating healthy surrounding tissue. Thus, the tumor cells bypass the induced by the TKI nutrient deficiency. Everolimus can be useful in such cases.

The compatibility of these agents seems to be good.

Lenvatinib

Tyrosine kinase inhibitor lenvatinib is approved in combination with everolimus for the treatment of patients with advanced RCC as a second-line treatment following previous vascular endothelial growth factor inhibitors (anti-VEGF) therapy. According to German S3-guideline, this combination in the situation described above represents a better option compared to the treatment with nivolumab or cabozantinib.

Cabozantinib

This oral targeted drug is aimed against different tyrosine kinases. According to the current evidence-based S3-guideline (2017) it is the best option after anti-VEGF therapy failure. Since 2018, cabozantinib has also been included in first-line therapy for patients with advanced renal cell carcinoma of medium or high risk.

Traditional immunotherapy

Traditional (unspecific) immunotherapy fights against kidney cancer using the patient's own immune system. Interferon alpha and interleukin-2, two messengers of the immune system, have been successfully by German oncologists used over the last 20 years. They activate our defense mechanisms, thereby inhibiting the growth of malignant cells. However, immunotherapy for RCC should be used in combination with other methods.

Interleukin-2 is still used for the IV or subcutaneous route of administration, but this immunotherapeutic drug only plays a very minor role in modern therapeutic landscape.

On the other hand, traditional immunotherapy, in particular interferon-alpha, can be combined with becacizumab. The monoclonal antibody bevacizumab is aimed against VEGF, and thus prevents the formation of new blood vessels feeding the tumor.



Bevacizumab is given intravenously every two weeks. The patient injects the interferon-alpha himself under the skin three times a week. Currently, this therapeutical combination is mainly offered to patients with a good prognosis.

Modern immunotherapy (cost from $5,000)

This therapy includes substances that do not directly attack the tumor but force the patient's leukocytes to fight against cancer by "releasing the brake of the immune system". This “brake” can be released by antibodies (so-called immune checkpoint inhibitors). Anti-PD-1 antibody nivolumab is now approved after pretreatment, i.e., as the second-line therapy. Oncologists expect relatively high response rate using this treatment in VEGF- and TKI-pretreated patients compared to older second-line regimens.

Nivolumab is administered every two weeks as an infusion and demonstrates an excellent tolerability. Immune-related side effects may not occur even months after the therapy.

Important considerations

• The clinical effect of the immunotherapeutic drugs depends to varying degrees on the histological type of renal cell carcinoma.
• The optimal duration of treatment is still unclear; there are data according to which the longest possible treatment may be useful to stop cancer spreading.
• The management of the very rare side effects requires a special experience. Treatment with immune checkpoint inhibitors requires special knowledge of the rare but potentially threatening side effects.

Radiation therapy for metastases

Radiation damages cancer DNA and vital cellular structures. This method is only used in advanced stages of the disease to treat metastases, to relieve discomfort and pain. Radiotherapy cannot completely cure kidney cancer.

What if cancer returns?

If the tumor occurs again (local recurrence), another surgery or ablation is performed. The physicians will discuss the pros and cons of reoperation with you. If metastases have already formed in other places, it must be decided whether they can be surgically removed. In some cases, the removal of secondary tumors can add several years of life.

Otherwise it may be better to choose conservative treatment (such as immunotherapy).

Palliative care

In the advanced stages of kidney cancer, the patient is often in pain, which can limit the quality of life. The most important in this case is to provide adequate pain relief. Pain ambulances and palliative care units, which are available at leading cancer clinics in Germany, have particularly competent specialists in this area. Prescription pain relievers (including strong opioid medications), antidepressants, anti-seizure drugs, steroids, innovative nerve-stimulating devices, physical therapy – the pain management will be tailored according to the latest recommendations.

If you want more information about kidney cancer treatment in Germany, visit our website and stay updated on the latest oncology developments!

© Analytical reviews and oncology news by K. Mokanov: clinical pharmacist and professional medical translator