The metastatic stage of the 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 with renal cell carcinoma develop metastases during the course of their disease, and 5 year survival for patients with metastatic renal cell carcinoma is between 5-15%, though 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 1 study has supported the use of cytoreductive nephrectomy in "some cases" of metastatic renal cell carcinoma, citing improved response rates to interleukin-2 immunotherapy and modestly prolonged survival.
Radiotherapy and chemotherapy have less of a role in therapy of renal cell carcinoma then in other malignancies; but they are still sometimes used in treatment of metastatic renal cell carcinoma.
Radiotherapy is used in bone metastases from renal cell carcinoma 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 from renal cell carcinoma.
Interleukin-2, has been the standard of care since the 1990s in metastatic renal cell carcinoma, as although response rates are low 7-16%, about half of patients that respond have long term disease free survival, and some of these patients may be cured of their disease.
However,the side effects of interleukin-2 are very severe, including decreased neutrophil function, increased risk of dissemenated infection, including central venous catheter infections, septicaemia, and bacterial endocarditis, 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.
Proleukin also can result in lethargy and somnolence; if interleukin-2 therapy is not discontinued lethargy may progress to coma. Interleukin-2 can also worsen pre-existing autoimmune diseases.
Exacerbation of scleroderma, diabetes mellitus, thyroiditis, inflammatory bowel disease, myesthinisa gravis, nephritis, and other autoimmune diseases have been reported.
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, vasodialation, diarrhea, vomiting, mouth sores, loss of appetite, dermatitis, dyspnea, thrombocytopenia, and anaemia.
Also, patients must be in good health with normal cardiovascular, hepatic, pulmanary,and neurological function to be treated with interleukin-2.
Recently, targeted therapys including torisel, nexavar, sutent, and bevacizumab have been developed, and all are now approved for the treatment of metastatic renal cell carcinoma.
Also, votrient was approved for the treatment of metastatic renal cell carcinoma in October 2009.
This is the sixth drug to be approved for metastatic renal cell carcinoma since 2005.
The last 3–5 years have seen dramatic improvements in treatment for those with metastatic renal cell carcinoma, Richard Pazdur, MD, director of the office of oncology drugs at the U.S. Food and Drug Administration (FDA).
However, despite these improvements in therapy, overall survival in metastatic renal cell carcinoma remains quite poor.
Currently, tumor vaccines and chemotheraputic, 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 metastatic renal cell carcinoma earliar improves survival or response to treatment.
Symptoms of metastatic renal cell carcinoma are often mistaken for other, less severe illness,and include: for bone metastases, pain, stiffness, bruit, and pathologic fracture; for liver metastases, abdominal pain, jaundice, elevations in AST and ALT, and vomiting, for lung metastases, cough, dyspnea, and abnormal chest radiograph.
Brain metastases produce diplopia, personality changes, headache, ataxia, vertigo, and seizures.
Systemic symptoms occur in some people with metastatic renal cell carcinoma, and include anorexia, fatigue, fever of unknown origin, weight loss, and malaise.
Given that many diseases can cause these symptoms, extensive testing is typically required to diagnose metastatic renal cell carcinoma.
Differential diagnoses include leukaemia, arthritis, any other neoplastic disease, locomotor ataxia, Lyme disease in the case of unexplained malaise, fatigue, and bone pain, and other chronic infections.
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