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Renal cancer is a relatively rare cancer accounting for approximately 3% of all adult malignancies. There are more than 5000 new cases diagnosed per year in the UK and the incidence is increasing. It most commonly affects people in their fifth to seventh decades with a male-to-female ratio of approximately 2:1.

Renal cell carcinoma (also known as clear cell carcinoma or hyper-nephroma) accounts for 80-85% of all kidney cancers. Papillary renal carcinoma constitutes approximately 10%, with the remainder including chromophobe and collecting duct carcinomas. Transitional cell carcinomas, squamous cell carcinomas and lymphomas can also arise in the kidney.

Risk factors for the development of Renal cell carcinoma include smoking, obesity, adult polycystic kidney disease and long-term renal replacement therapy. Approximately 1% of RCCs are hereditary, the most commonly associated syndrome being the von Hippel-Lindau syndrome. It has recently been demonstrated that most cases of sporadic Renal cell carcinoma have mutations in the von Hippel-Lindau gene, located on the short arm of chromosome three, which normally acts as a tumour suppressor gene.

The most commonly used method of staging renal cancer is the Robson staging system. Stage of disease and prognosis are closely linked. For tumours confined to the kidney (stage I) and with tumours that involve perinephric fat (stage II) the 5-year survival is 50-80% [1]. In patients with distant metastatic disease (stage Intravenous) the median survival is just 8 months with a 5-year survival of less than 10%.

Approximately one quarter of patients present with metastatic disease. A further 30-40% of patients present with apparently localized disease but eventually develop distant metastases . The lung is the most common site of metastasis (50-60%), followed by bone (30-40%), liver (30-40%) and brain (5%).

Whilst radical nephrectomy can be curative in patients presenting with localized disease, the treatment options available to those with metastatic disease remain limited and far from ideal.

Renal cell carcinoma is notoriously resistant to conventional chemotherapy agents and these drugs are not commonly used in disease management. Radiotherapy has a useful palliative role in a limited capacity, used mainly in the treatment of painful bony metastases, localized subcutaneous metastases and brain metastases. Hormonal agents, in particular medroxyprogesterone acetate and tamoxifen (more commonly used in mainland Europe) are often used to palliate the systemic effects of cancer. Their anticancer activity however is very limited, with objective response rates of approximately 1%.

Attention has largely focused on the use of biological agents. Interferon-alpha (IFN-a) and interleukin-2 (IL-2) have both been used extensively in Renal cell carcinoma over the past 2 decades, with encouraging results. It is well established that the use of such agents, termed immunotherapy, can induce complete and durable responses in a small number of patients. In the UK, IFN-a is now widely accepted as standard first-line therapy.

Whilst some progress has been made in recent years, the prognosis for patients with metastatic (m) Renal cell carcinoma remains poor. Thus there remains an urgent need for the development of novel, more active agents. A greater understanding of the biology of this and other cancers has lead to the recent development of a number of new and promising strategies.

Principles of therapy

Drugs available

Future developments

Conclusions

Renal cancer remains amongst the more difficult of cancers to treat. Effective therapies for the majority of patients with mRCC have not been found. Traditional chemotherapy drugs are ineffective and are not commonly used.

Currently, immunotherapy offers the best hope for patients. response rates may be increased by nephrectomy and should be considered before commencing systemic treatment. Standard first-line therapy in the UK is single-agent IFN-a, which has a modest overall RR of approximately 15%.

Atzpodien’s triple therapy is a convenient, relatively well tolerated, outpatient-based regime that has shown high response rates in some studies. The Medical Research Council RE04 study will determine whether it confers a real advantage over single-agent interferon.

Beyond this, there are a wealth of new approaches being developed. A better understanding of the biology of cancer has lead to several novel therapies. Ultimately, success is likely to come from using a combination of agents that simultaneously target the multiple processes that drive the cancer cell.