A localised renal carcinoma is always considered for surgical removal; the whole kidney is removed (nephrectomy) so long as the other kidney is functioning normally and can take over the body’s overall renal function. If the tumour is localised to the kidney then such surgery may alone result in a 67% cure rate. The use of adjuvant systemic therapy (e.g. immunotherapy, see below) after the operation to try to reduce the subsequent incidence of relapse has not been proven and is not standard therapy. There may be a case for nephrectomy even if there is evidence of metastatic disease; some evidence having been assembled to suggest that, particularly lung, metastatic disease may be more likely to respond to other therapy (even to rarely involute without further therapy) if the large mass of primary tumour in the kidney is removed.
For metastatic spread, the options are limited as chemotherapy has a poor track record in this disease. However, for some years, immunotherapy with interferon in particular has had some success with response rates of 15-20% in metastatic disease; the response of lung metastatic disease exceeds that of bone disease; the addition of interleukin probably improves the response rate of interferon alone. The figure shows (left panel) lung metastases from kidney cancer on a chest x-ray and their disappearance after immunotherapy (right panel), demonsatrating the very good (but temporary) responses that can be achieved. In recent years new molecularly based therapies have been developed and the drugs sunitinib and sorafenib and foremost amongst these. They are tyrosine kinase inhibitors that inhibit signalling pathways between aberrant oncogenes and cell mitotic activity.
With the realisation of the common involvement of the VHL gene, has come great interest in the therapeutic use of agents that inhibit VEGF and some of the cell growth promoting factors that are usually under the inhibitory control of the VHL gene. Thus, sunitinib and sorafinib are two such medical therapies that have replaced interferon and interleukin for first place systemic therapy in this disease.
Thus, the first systemic drug therapy for relapsed kidney cancer is now a tyrosine kinase inhibitor such as sunitinib or sorafenib (or newer tyrosine kinase inhibitors), followed by an m-TOR inhibitor, possibly backed up by a VEGF inhibitor such as bevacizumab. Immunotherapy is kept in reserve.
First line therapy would now usually be with sunitinib for all advanced clear cell kidney cancer patients. If the patient responds, he/she continues this therapy for a year or so - it is a simple tablet.
Bevacizumab is an antibody that inhibits tumour growth by blocking the formation of new tumour blood vessels. It can be considered for first-line therapy in combination with interferon-α in patients with advanced and/or metastatic RCC.
Sorafenib inhibits the development of tumour blood vessels and tumour cell proliferation. It may be considered for the treatment of patients with advanced RCC whose condition has failed to respond to interferon-α or interleukin-2 therapy or who are considered unsuitable for such therapy.
Sunitinib also inhibits the development of tumour blood vessels and tumour cell proliferation. Temsirolimus/ everolimus or other m-TOR inhibitors are selective inhibitors of a protein that regulates a signalling pathway controlling growth factor-induced cell proliferation. Sunitib and Temsirolimus may be considered for the treatment of patients with advanced and/or metastatic RCC, temsirolimus/everolimus usually being trialled after a trial period on sunitinib.
When/if the patient relapses after such therapy, there is little that alters the natural history of the disease further; thus far, conventional chemotherapy has not had success in treating this particular cancer..
Following the observation that oestrogens could promote the incidence of renal carcinoma in hamsters, it was usual to prescribe hormonal therapy (particularly progestogens) in therapy of metastatic disease and it is true that occasional responses have been well documented following this approach. However, it is a rare and poorly maintained response for the most part.
Occasionally, radiotherapy to the flank/loin after surgery is employed if the cancer is particularly aggressive in the flank region but it has not been shown to alter the survival statistics significantly. Local radiotherapy for painful bony metastases or for brain metastases is good for the immediate problem that they bring but do not treat the problem as a whole.