Renal Cell Carcinoma - Metastatic Renal Cell Carcinoma

Metastatic Renal Cell Carcinoma

The metastatic stage of renal cell carcinoma occurs when the disease invades and spreads to other organs. It is most likely to spread to neighboring lymph nodes, the lungs, the liver, the bones, or the brain. Metastatic renal cell carcinoma presents a special challenge to oncologists, as about 70% of patients develop metastases during the course of their disease, and 5 year survival for patients with metastatic renal cell carcinoma is between 5 and 15%, although it is much improved if metastatectomy and nephrectomy to remove all visible disease is performed. Even if metastases are not removed, cytoreductive nephrectomy is sometimes used in the treatment of metastatic renal cell carcinoma, and at least one study has supported the use of this operation in "some cases", citing improved response rates to interleukin-2 immunotherapy and modestly prolonged survival.

Radiotherapy and chemotherapy have less of a role in the treatment of renal cell carcinoma than in other malignancies; but they are still sometimes used in treatment of the metastatic disease. Radiotherapy is used in in cases of bone metastases, to reduce pain and lower the risk of pathologic fracture, in patients with brain metastases, and to palliate symptoms of metastatic disease to the liver, adrenals, or lungs.

Interleukin-2 has been the standard of care since the 1990s in metastatic renal cell carcinoma, as, although response rates are low, about half of patients that respond have long term disease-free survival, and some of these patients may be completely cured. However,the side effects of interleukin-2 are severe, including decreased neutrophil function, increased risk of disseminated infection, including central venous catheter infections, septicaemia, bacterial endocarditis, and capillary leak syndrome, which can result in myocardial infarction, renal failure, angina, hypotension, reduced organ perfusion, altered mental status, pulmonary failure requiring intubation, cardiac arrhythmias, edema, and gastrointestinal bleeding.

The use of proleukin can also result in lethargy and somnolence; if interleukin-2 therapy is not discontinued lethargy may progress to coma. Interleukin-2 can also worsen preexisting autoimmune diseases. Neurological side effects can also occur, and include ataxia, cortical blindness, hallucinations, psychosis, speech problems, and coma. Other side effects include abdominal pain, rigors, fever, malaise, asthenia, acidosis, tachycardia, vasodilatation, diarrhea, vomiting, mouth sores, loss of appetite, dermatitis, dyspnea, thrombocytopenia, and anaemia. Therefore, patients must be in good health with normal cardiovascular, hepatic, pulmonary,and neurological function to be treated with interleukin-2.

Recently, targeted therapies such as torisel, nexavar, sutent, votrient, and bevacizumab, have been developed, and all are now approved for the treatment of metastatic renal cell carcinoma. The three to five years up to 2009 saw dramatic improvements in treatment for those with metastatic renal cell carcinoma. However, despite these improvements in therapy, overall survival remains poor.

Currently, tumor vaccines and chemotherapeutic, biologic, and immunologic agents are being researched in the treatment of metastatic renal cell carcinoma, and some appear promising. It is not known whether or not detecting metastases earlier improves survival or response to treatment.