Many people with kidney cancer do not have obvious symptoms. Some people have very general, perhaps vague, symptoms such as tiredness, loss of appetite, weight loss or persistent fever (often expressed in night sweats). But of course these symptoms can be caused by many other conditions apart from kidney cancer. A more specific symptom that requires careful investigation is blood in the urine (haematuria). This is the most common symptom of kidney cancer, but there can be other reasons for loss of blood, e.g. infections, kidney stones, prostate problems. Any lump or swelling in the area of the kidney, and any persistent low back pain, should also be taken seriously.

If a kidney tumour is large, it can sometimes by felt by hand, but usually tumours are too small to be detected in this way. In some cases low blood counts (anaemia) may be an indication of kidney cancer. Where the disease has spread beyond the kidney, symptoms may first appear from secondary tumours (metastases). Breathlessness and coughing blood, for example, may be symptoms of tumours that have spread to the lungs from the kidney. In this case the secondary tumours are classified as kidney cancer and not lung cancer.

A patient whose kidney cancer is confined to the kidney and has not spread into the lymph nodes or to other organs of the body stands the best chance (in statistical terms) of long-term survival. Some patients in this category will have their kidney and primary tumour removed by surgery and will never have any recurrence of the disease. In that sense they may be deemed ‘cured’.

However, as with all cancers, there can never be complete certainty that cancer cells, carried through the lymphatic system and the blood, will not form into secondary tumours (metastases). Regular check-ups are essential for all kidney cancer patients, including those who, after surgery, are apparently free of disease.

According to medical statistics, patients in whom the disease has spread beyond the kidney are less likely to do well. If the disease has spread to one or more organs, such as the lungs or the liver, it is vitally important, following surgery to remove the kidney and primary tumour, to have access to treatment that can stabilise or even eliminate secondary tumours. Some patients with secondary tumours respond well to further treatment (which is usually in the form of immunotherapy); others do not respond or respond only temporarily. We do not fully understand the reasons for this variation.

One significant factor is that kidney cancer cells vary in their level of aggressiveness from patient to patient. This relates mainly to the degree of abnormality of the cells, i.e. their degree of difference from normal cells. The higher the ‘grade’ of the kidney cancer cells, i.e. the more aggressive they are, the more likely they are to spread quickly and metastasise. Some patients with secondary tumours live with their disease for a long time. A small proportion are ‘cured’ by treatment in the sense that their secondary tumours disappear completely. Even in these cases, however, a recurrence can never be ruled out.

Surgery is usually the first-line treatment for kidney cancer and may be all that is required if the cancer is at an early stage. In an operation called a ‘radical nephrectomy’, the whole kidney is removed along with the primary tumour and the surrounding fatty tissue. Local lymph nodes are also removed to help determine if the cancer has spread. Removal of the adrenal gland on the side of the tumour may also be necessary, depending on the site and size of the tumour.

If the tumour is small, a partial nephrectomy may be performed, whereby only the part of the kidney containing the cancer is removed. If the cancer has spread beyond the kidney to other parts of the body, in some cases further surgery may be considered appropriate to remove secondary tumours, e.g. from the lungs.

Surgeons sometimes perform a procedure known as ‘arterial embolisation’, which aims to cut off the primary tumour’s main blood supply. A special gelatin sponge or other material is injected into the main blood vessels that carry blood to the kidney. This procedure can be used before an operation to shrink a tumour and make surgery easier, or it may be used to restrict further tumour growth, alleviate pain or stop bleeding where a full nephrectomy is not considered to be advisable. A nephrectomy has traditionally been performed with full open surgery, but in recent years there has been increasing use in appropriate cases of ‘keyhole’ surgery using a small incision and an instrument known as a ‘laparoscope’. It is important that all patients should discuss the surgical options with a specialist urologist.

Von-Hippel-Lindau syndrome (von-Hippel-Lindau disease) is a rare condition that affects about 1 in 40,000 people in the UK.

It is due to a faulty gene. In 4 out of 5 cases the gene is inherited from one or other parent, but in 1 in 5 people with von-Hippel-Lindau syndrome it occurs as a result of a new gene change (mutation), with no family history.

The condition leads to changes in the way some blood vessels are formed, and this causes tumours of blood vessels (called haemangioblastomas) in certain parts of the body. The places most often affected are the brain (particularly a part of the brain called the cerebellum), the spinal cord, and the retina (the lining of the back of the eye). These tumours are non-cancerous (benign), but sometimes can be quite serious because of where they develop.

More information on von-Hippel-Lindau syndrome can be found
on the VHL Family Alliance website

More than 6,600 people are diagnosed with kidney cancer each year in the UK. Kidney cancer causes around 3,600 deaths each year in the UK.

In adults in England and Wales almost 90% of malignant kidney tumours arise in the renal parenchyma and the renal pelvis. Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, causing up to 85 percent of all kidney cancers

Kidney cancer affects both men and women with a ratio of 5 new diagnoses in men for every 3 in women. Between 1975 and 2002, the incidence of kidney cancer in the UK has almost doubled for both men and women aged over 65 years.

In men, incidence rates increased by 79% between 1975 and 2002 (from 7.1 in 100,000 in 1975 to 12.7 per 100,000 in 2002), and by 90% in women (from 3.2 to 6.1 per 100, 000) over the same time period, mainly affecting men over 65 and women over 55 years.

When launched in July 2006, sorafenib was the first new kidney cancer treatment in Europe for over 10 years.

Mechanism of Action
Sorafenib is an oral multi-kinase inhibitor that targets both the tumour cell and tumour vasculature. In preclinical models, sorafenib targeted members of two classes of kinases (tyrosine kinases and serine/threonine kinases) known to be involved in both tumour cell proliferation (tumour growth) and tumour angiogenesis (tumour blood supply) - two important cancer growth activities. These kinases included RAF kinase, VEGFR-2, VEGFR-3, PDGFR-β, c-KIT and FLT-2.

Indication
Sorafenib, (200 mg film-coated tablets) is indicated for the treatment of patients with advanced renal cell carcinoma who have failed prior interferon-alpha or interleukin-2 based therapy and also 1st line when patients are considered unsuitable for such therapy.

Sorafenib is being evaluated as a single agent in a Phase III clinical trial for the treatment of advanced hepatocellular carcinoma (HCC), or liver cancer, a study that has completed enrolment. A Phase III clinical trial of Nexavar combined with carboplatin and paclitaxel in non-small cell lung cancer (NSCLC) for treatment-naive patients was initiated in the first half of 2006. In addition to company-sponsored trials, there are a number of sorafenib studies being sponsored by government agencies, cooperative groups, and individual investigators.

Sutent is a novel, oral, multi-targeted cancer therapy that selectively targets multiple receptor tyrosine kinases (RTKs) involved in tumor growth, angiogenesis and the progression of cancer. By inhibiting these RTKs, Sutent targets multiple signaling pathways resulting in a dual action anti-proliferative and anti-angiogenic effect, which may lead to tumour regression and disease stabilisation.

The recommended starting dose for Sutent is 50mg once daily for four weeks followed by two weeks off. The dose can be modified in 12.5mg increments not to exceed 87.5mg or decrease below 37.5mg. Sutent is available in 12.5 mg, 25mg, and 50mg capsules.

Adverse events (AEs) were generally mild to moderate. Most adverse events were reversible, and generally did not result in discontinuation. In clinical trials, the most common treatment related adverse events (>20%) included fatigue; gastrointestinal disorders, such as diarrhoea, nausea, stomatitis, dyspepsia, and vomiting; skin discolouration; dysgeusia (loss of taste); and anorexia. Fatigue, hypertension and neutropenia were the most common grade 3 treatment related adverse events. Increased lipase (2%) was the most common grade 4 treatment related adverse event.

The most important treatment related serious adverse events associated with Sutent treatment of solid tumour patients were pulmonary embolism (1%), thrombocytopoenia (1%), tumor haemorrhage (0.9%), febrile neutropoenia (0.4%), and hypertension (0.4%). Patients should be screened for hypertension and appropriately controlled with medical management. Temporary suspension of Sutent is recommended in patients with severe hypertension that is not controlled with medical management.

Developed by Pfizer, Sutent is being studied alone and in combination with other medicines as a potential treatment for a number of other solid tumours, including breast, lung, prostate, and colorectal cancers. More than 3,000 patients have been treated with Sutent.