If it is only in the kidneys, which is about 40% of cases, Renal Cell Carcinoma (RCC) can be cured roughly 90% of the time with surgery.
If it has spread outside of the kidneys, often into the lymph nodes or the main vein of the kidney, then it must be treated with adjunctive therapy, including cytoreductive surgery.
RCC is resistant to chemotherapy and radiotherapy in most cases, but does respond well to immunotherapy with interleukin-2 or interferon-alpha, biologic, or targeted therapy. In early stage cases, cryotherapy and surgery are the preferred options.
Watchful waiting
Small renal tumors (< 4 cm) are treated increasingly by way of partial nephrectomy when possible. Most of these small renal masses manifest indolent biological behavior with excellent prognosis.
More centers of excellence are incorporating needle biopsy to confirm the presence of malignant histology prior to recommending definitive surgical extirpation.
In the elderly, patients with co-morbidities and in poor surgical candidates, small renal tumors may be monitored carefully with serial imaging.
Most clinicians conservatively follow tumors up to a size threshold between 3–5 cm, beyond which the risk of distant spread (metastases) is about 5%.
Surgery
Surgical removal of all or part of the kidney (nephrectomy) is recommended. as well as resection of a solitary metastatic lesion. Kidneys are sometimes embolized prior to surgery to minimize blood loss
Medications
RCC elicits an immune response, which occasionally results in dramatic spontaneous remissions. This has encouraged a strategy of using immunomodulating therapies, such as cancer vaccines and interleukin-2 (IL-2), to reproduce this response.
IL-2 has produced "durable remissions" in a small number of patients, but with substantial toxicity.
Another strategy is to restore the function of the VHL gene, which is to destroy proteins that promote inappropriate vascularization.
Bevacizumab, an antibody to VEGF, has significantly prolonged time to progression, but phase 3 trials have not been published. Sunitinib (Sutent), sorafenib (Nexavar), and temsirolimus, which are small-molecule inhibitors of proteins, have been approved by the U.S. F.D.A.
Treatment with tyrosine kinase inhibitors including nexavar, pazopanib, and rapamycin have shown promise in improving the prognosis for advanced RCC since 2004.
Sorafenib, a protein kinase inhibitor, was FDA approved in December 2005 for treatment of advanced renal cell cancer.
A month later, Sunitinib was approved as well. Sunitinib—an oral, small-molecule, multi-targeted (RTK) inhibitor—and sorafenib both interfere with tumor growth by inhibiting angiogenesis as well as tumor cell proliferation.
Sunitinib appears to offer greater potency against advanced RCC, perhaps because it inhibits more receptors than sorafenib.
However, these agents have not been directly compared against one another in a single trial. the first Phase III study comparing an RTKI with cytokine therapy was published in the ''New England Journal of Medicine''.
This study showed that Sunitinib offered superior efficacy compared with interferon-α. Progression-free survival (primary endpoint) was more than doubled.
The benefit for sunitinib was significant across all major patient subgroups, including those with a poor prognosis at baseline. 28% of sunitinib patients had significant tumor shrinkage compared with only 5% of patients who received interferon-α.
Although overall survival data are not yet mature, there is a clear trend toward improved survival with sunitinib. Patients receiving sunitinib also reported a significantly better quality of life than those treated with IFNa.
Temsirolimus (CCI-779) is an inhibitor of mTOR kinase (mammalian target of rapamycin) that was shown to prolong overall survival vs. interferon-α in patients with previously untreated metastatic renal cell carcinoma with three or more poor prognostic features.
The results of this Phase III randomized study were presented at the 2006 annual meeting of the American Society of Clinical Oncology (www.ASCO.org).
Date of Approval: March 30, 2009
Company: Novartis AG
Treatment for: Renal Cell Carcinoma
Afinitor (everolimus) is an oral once-daily inhibitor of mTOR indicated for the treatment of patients with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib.
Afinitor approved in US as first treatment for patients with advanced kidney cancer after failure of either sunitinib or sorafenib - March 30, 2009
Thalomid and Revlimid have been studied in the treatment of renal cell carcinoma.
Chemotherapy
Most of the currently available cytostatics are ineffective for the treatment of RCC. Their use can not be recommended for the treatment of patients with metastasized RCC,as response rates are very low,often just 5-15%,and most responses are short lived.
However, issues of tumor immunosuppression and lack of identified tumor-associated antigens must be addressed before vaccine therapy can be applied successfully in advanced renal cell cancer.
Further Reading
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