Renal cell carcinoma is a malignant disease of the kidney.

Malignant kidney tumours account for around 3% of all malignant neoplasms in adults. In Germany, around 5700 women and 8300 men are newly diagnosed with kidney cancer every year. The average age of onset is 63 years for men and 67 years for women. Men are about 1.5 times more likely to develop the disease than women.

Malignant tumours in the kidney are named after the tissue from which the tumour originated. Around 90% of all kidney tumours are renal cell carcinomas. The remaining 10% are sarcomas, nephroblastomas (Wilms tumour), embryonal carcinomas or neuroblastomas.

The rather rare renal pelvic carcinomas arise from the mucous membrane of the urinary tract and are therefore not renal carcinomas, but belong to the bladder or ureteral carcinomas and are treated differently accordingly.

Renal cell carcinomas usually originate from the cells of the urinary tubules (tubule system), rarely from the cells of the collecting duct system.

In most cases, only one kidney is affected by the tumour. In only about 1.5% of cases are both kidneys affected.

The causes of kidney cancer are not yet clearly understood. However, a number of different factors can increase the risk of developing renal cell carcinoma.

Smoking, obesity and hormonal factors appear to play a role as risk factors. Exposure to cadmium, lead, petrochemical substances, tar and wood preservatives are also considered risk factors. Confirmed factors are chronic renal insufficiency, a positive family history, von Hippel-Lindau's disease and tuberous sclerosis.

Kidney carcinomas rarely cause symptoms in the early stages and are therefore usually discovered by chance, e.g. during an ultrasound examination. Pain in the flank or back, blood in the urine (reddish to brown discolouration) can be an indication of kidney disease, as can colic, weight loss, anaemia, fever, high or low blood pressure, intestinal problems or constant fatigue.

Early detection offers the best chance of a cure for malignant tumours.

The most important examinations for the detection of renal carcinoma include the medical history and physical examination, laboratory tests (blood), ultrasound examination and computerised tomography (CT).

Further examinations such as X-ray examination, magnetic resonance imaging (MRI), angiography (visualisation of the blood vessels), urography or skeletal scintigraphy may also be necessary.

In order to determine the most suitable therapy, the above-mentioned diagnostics must be used to determine exactly how far the tumour has spread before therapy begins, i.e. the tumour stage is determined. The TNM classification is used for this purpose (see table below).

T stands for the size and extent of the primary tumour, N stands for the number of affected regional lymph nodes and M stands for the occurrence and localisation of distant metastases (tumour metastases).

A final assessment of the TNM stage is only possible after tumour surgery.

Two further criteria are decisive for further therapy. Microscopic examination of the tumour tissue provides an indication of the malignancy of the tumour. This involves comparing the similarity of the cancer cells with the organ cells (see table below).

Secondly, it is of decisive importance whether the tumour could be completely removed (see table below).

The treatment methods depend on the stage of the tumour. The earlier a renal cell carcinoma is detected, the more favourable the prognosis for the patient. However, the patient's age and general state of health are also taken into account when choosing a therapy.

Curative surgery

Kidney removal (nephrectomy) with removal of lymph nodes

The standard therapy is the complete removal of the tumour-infected kidney. This provides a chance of cure for renal cell carcinoma. The function of the removed kidney is then taken over by the remaining healthy kidney.

In some patients, it is possible to remove the kidney by laparoscopy (keyhole technique).

Partial kidney removal

The partial removal of tumours up to a diameter of 7 cm (stage pT1) is now an accepted procedure and promises the same survival rate as the complete removal of the kidney.

In any case, organ-preserving tumour removal is aimed for in patients who only have one kidney left or the second kidney is not working properly, as these patients would otherwise have to undergo regular dialysis (blood washing). If the tumour can be completely removed by this operation, further therapy is not necessary and the patient also has a chance of recovery.

Palliative (symptom-relieving) surgery

Tumour resection

Approximately 30% of all renal cell carcinoma patients already have lymph node or distant metastasis at the time of diagnosis. This is referred to as a palliative situation. There are indications that tumour removal in a palliative situation can bring a survival advantage if followed by systemic therapy. Tumour removal can therefore also be offered in the metastatic stage for patients who are not at significantly increased risk of surgery.

Resection of metastases

If there are only isolated distant metastases, e.g. in the lungs, metastasectomy may be advisable. This can reduce symptoms and in some cases even achieve a cure.

Special form of therapy - tumour embolisation

Tumour embolisation is mainly performed on older patients who can no longer be operated on. The blood vessel leading to the kidney is closed off by a catheter so that the tumour is cut off from the blood supply and can no longer continue to grow or even regress. Unfortunately, this effect is only short-lived as the blood finds new routes.

Course of the disease (relapse, metastases)

If a relapse of the disease occurs with metastases in several places in the body, various substances can be used to suppress tumour growth.

Chemotherapy

Cytostatic drugs are intended to kill rapidly growing tumour cells in the body. However, chemotherapy is virtually ineffective for renal cell carcinoma and is therefore not used.

Immunotherapy

The human immune system has the task of fighting off foreign substances, e.g. viruses or bacteria, and under certain circumstances it can even destroy pathologically altered cells, e.g. cancer cells.

The aim of immunotherapy is to stimulate the immune system with certain substances (cytokines: e.g. interferons, interleukins) so that tumour cells can be recognised, attacked and eliminated by the patient's own body.

Immunotherapy with interferon or interleukins is one of the standard therapies in the treatment of metastatic renal cell carcinoma, but is only used extremely rarely nowadays, although high-dose interleukin-2 therapy can lead to a cure in a limited percentage (approx. 7%) of affected patients, even in the metastatic stage.

The side effects of this immunotherapy can be similar to the symptoms of flu (fever, chills, night sweats, aching limbs).

Since 2016, a further development of conventional immunotherapy in the form of a venous antibody therapy with the so-called PD-1 inhibitor nivolumab has been approved for the treatment of metastatic renal cell carcinoma after systemic pre-treatment with another drug. By binding to the PD-1 receptor of the immune cells, nivolumab stimulates the immune system and kills tumour cells. In a large randomised study, nivolumab treatment led to a partial regression of the tumour disease in 23% of cases and a complete regression in 1% of cases. Nivolumab led to an extension of survival by approx. 5 months. Research is currently underway to determine whether a combination of two antibody therapies (nivolumab + ipilimumab) is also superior to the current standard therapy with tyrosine kinase inhibitors as initial treatment for metastasised kidney cancer; results are expected in 2018

Molecular, targeted therapy "Targeted Therapy"

Due to the upregulation of a growth factor for vascularisation (vascular endothelial growth factor, VEGF) in renal cell carcinomas, this is a promising starting point for molecular targeted therapy. Other target structures are the receptor for platelet derived growth factor (PDGFR) and a kinase with a key function in the cell, the "mammalian target of rapamycin kinase" (mTOR).

In recent years, therapeutics have been developed that intervene at various points in this signalling cascade and have led to a fundamental change in therapeutic strategies. In principle, antibodies such as bevacizumab (Avastin®), tyrosine kinase inhibitors (TKIs) such as sunitinib (Sutent®), pazopanib (Votrient®), sorafenib (Nexavar®), axitinib (Inlyta®) and mTOR inhibitors such as temsirolimus (Torisel®) or everolimus (Afinitor®) should be distinguished here. Response rates (significant reduction in tumour size) of up to 40% have been achieved in larger studies.

Sutent®, pazopanib (Votrient®), sorafenib (Nexavar®), axitinib (Inlyta®) and everolimus (Afinitor®) are tablets that can be taken at home. However, regular consultations with oncologically experienced doctors are also necessary here in order to control or prevent side effects in advance.

Palliative (symptom-relieving) radiotherapy

Renal cell carcinomas are relatively insensitive to radiation. For this reason, radiotherapy is almost only used at an advanced stage to relieve the pain of metastases

If a relapse of the disease occurs with metastases in several places in the body, various substances can be used to suppress the tumour growth.

Chemotherapy

Cytostatic drugs are intended to kill fast-growing tumour cells in the body. However, chemotherapy is virtually ineffective for renal cell carcinomas and is therefore not used.

Immunotherapy

The human immune system has the task of fighting off foreign substances, e.g. viruses or bacteria, and under certain circumstances it can even destroy pathologically altered cells, e.g. cancer cells.

The aim of immunotherapy is to stimulate the immune system with certain substances (cytokines: e.g. interferons, interleukins) so that tumour cells can be recognised, attacked and eliminated by the patient's own body.

Immunotherapy with interferon or interleukins is one of the standard therapies in the treatment of metastatic renal cell carcinoma, but is now only used extremely rarely, although high-dose interleukin-2 therapy can lead to a cure in a limited percentage (approx. 7%) of affected patients, even in the metastatic stage.

The side effects of this immunotherapy can be similar to the symptoms of flu (fever, chills, night sweats, aching limbs).

Since 2016, a further development of conventional immunotherapy in the form of a venous antibody therapy with the so-called PD-1 inhibitor nivolumab has been approved for the treatment of metastatic renal cell carcinoma after systemic pre-treatment with another drug. By binding to the PD-1 receptor of the immune cells, nivolumab stimulates the immune system and kills tumour cells. In a large randomised study, nivolumab treatment led to a partial regression of the tumour disease in 23% of cases and a complete regression in 1% of cases. Nivolumab led to an extension of survival by approx. 5 months. Research is currently underway to determine whether a combination of two antibody therapies (nivolumab + ipilimumab) is also superior to the current standard therapy with tyrosine kinase inhibitors as initial treatment for metastasised kidney cancer; results are expected in 2018

Molecular, targeted therapy "Targeted Therapy"

Due to the upregulation of a growth factor for vascularisation (vascular endothelial growth factor, VEGF) in renal cell carcinomas, this is a promising starting point for molecular targeted therapy. Other target structures are the receptor for platelet derived growth factor (PDGFR) and a kinase with a key function in the cell, the "mammalian target of rapamycin kinase" (mTOR).

In recent years, therapeutics have been developed that intervene at various points in this signalling cascade and have led to a fundamental change in therapeutic strategies. In principle, antibodies such as bevacizumab (Avastin®), tyrosine kinase inhibitors (TKIs) such as sunitinib (Sutent®), pazopanib (Votrient®), sorafenib (Nexavar®), axitinib (Inlyta®) and mTOR inhibitors such as temsirolimus (Torisel®) or everolimus (Afinitor®) should be distinguished here. Response rates (significant reduction in tumour size) of up to 40% have been achieved in larger studies.

Sutent®, pazopanib (Votrient®), sorafenib (Nexavar®), axitinib (Inlyta®) and everolimus (Afinitor®) are tablets that can be taken at home. However, regular consultations with oncologically experienced doctors are also necessary here in order to control or prevent side effects in advance.

Palliative (symptom-relieving) radiotherapy

Renal cell carcinomas are relatively insensitive to radiation. For this reason, radiotherapy is almost only used at an advanced stage to relieve the pain of metastases

Aftercare

Forfollow-up care, a scheme based on the guidelines of the DGU and the German Cancer Society can be used after surgical tumour removal.

*According to the EAU guidelines, CT is only recommended in the case of an increased risk of contralateral metachronous RCC (chromophilic RCC, Von Hippel-Lindau disease) and in the case of partial kidney resection (imperative and elective) and locally advanced T3 and T4 tumours.

Rehabilitation

The necessity of inpatient follow-up treatment (AHB) should be decided on an individual basis, as there are no disease-specific rehabilitation measures for renal cell carcinoma.

The decisive factor for the prognosis of renal cell carcinoma is metastasis. The median survival probability is 19 months after the appearance of metastases, but varies greatly from individual to individual. Thanks to the use of sonography, most tumours are now detected at an early stage; the prognosis then depends mainly on the presence of lymph node or organ metastases and less on the tumour category or tumour size.