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| | __NOTOC__ |
| '''For patient information click [[{{PAGENAME}} (patient information)|here]]''' | | '''For patient information click [[{{PAGENAME}} (patient information)|here]]''' |
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| {{DiseaseDisorder infobox | | | {{Renal cell carcinoma}} |
| Name = Renal cell carcinoma |hh
| | {{CMG}}; {{AE}} {{YD}}, {{SSK}}, {{SC}} |
| ICD10 = {{ICD10|C|64||c|64}} |blah
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| ICD9 = {{ICD9|189.0}} |
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| ICDO = {{ICDO|8312|3}} |
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| Image = Renal clear cell ca (1) Nephrectomy.jpg |
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| Caption = Histopathologic image of clear cell carcinoma of the kidney. Nephrectomy specimen. Hematoxylin-eosin stain. |
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| OMIM = |
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| OMIM_mult = |
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| MedlinePlus = 000516 |
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| DiseasesDB = 11245 |
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| }} | |
| {{Kidney cancer}} | |
| {{SCC}} | |
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| '''Contributors:''' [[C. Michael Gibson]], M.S., M.D., [[User:zorkun|Cafer Zorkun]] M.D., PhD.
| | {{SK}} RCC; Renal cell CA; Kidney cancer; Kidney carcinoma; Kidney CA; Grawitz tumor; Hypernephroma |
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| {{Editor Join}}
| | ==[[Renal cell carcinoma overview|Overview]]== |
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| '''''Synonyms and Key Words:''''' RCC, renal cell, renal cell CA, renal cell carcinoma, kidney cancer, kidney carcinoma, kidney CA, Grawitz tumor, hypernephroma
| | ==[[Renal cell carcinoma historical perspective|Historical Perspective]]== |
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| ==[[Kidney cancer overview|Overview]]== | | ==[[Renal cell carcinoma classification|Classification]]== |
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| ==[[Kidney cancer historical perspective|Historical Perspective]]== | | ==[[Renal cell carcinoma pathophysiology|Pathophysiology]]== |
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| ==[[Kidney cancer pathophysiology|Pathophysiology]]== | | ==[[Renal cell carcioma causes|Causes]]== |
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| ==[[Kidney cancer epidemiology and demographics|Epidemiology & Demographics]]== | | ==[[Renal cell carcinoma differential diagnosis|Differentiating Renal cell carcinoma from other Diseases]]== |
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| ==[[Kidney cancer risk factors|Risk Factors]]== | | ==[[Renal cell carcinoma epidemiology and demographics|Epidemiology and Demographics]]== |
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| ==[[Kidney cancer screening|Screening]]== | | ==[[Renal cell carcinoma risk factors|Risk Factors]]== |
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| ==[[Kidney cancer causes|Causes]]== | | ==[[Renal cell carcinoma screening|Screening]]== |
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| ==[[Kidney cancer differential diagnosis|Differentiating Kidney cancer]]== | | ==[[Renal cell carcinoma natural history, complications, and prognosis|Natural History, Complications and Prognosis]]== |
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| ==[[Kidney cancer natural history|Complications, & Prognosis]]==
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| ==Diagnosis== | | ==Diagnosis== |
| [[Kidney cancer history and symptoms|History and Symptoms]] | [[Kidney cancer physical examination|Physical Examination]] | [[Kidney cancer staging|Staging]] | [[Kidney cancer laboratory tests|Laboratory tests]] | [[Kidney cancer electrocardiogram|Electrocardiogram]] | [[Kidney cancer x ray|X Rays]] | [[Kidney cancer CT|CT]] | [[Kidney cancer MRI|MRI]] [[Kidney cancer echocardiography or ultrasound|Echocardiography or Ultrasound]] | [[Kidney cancer other imaging findings|Other images]] | [[Kidney cancer other diagnostic studies|Alternative diagnostics]] | | [[Renal cell carcinoma staging|Staging]] | [[Renal cell carcinoma history and symptoms|History and Symptoms]] | [[Renal cell carcinoma physical examination|Physical Examination]] | [[Renal cell carcinoma laboratory findings|Laboratory Findings]] | [[Renal cell carcinoma CT|CT]] | [[Renal cell carcinoma MRI | MRI]] | [[Renal cell carcinoma echocardiography or ultrasound| Ultrasound]] | [[Renal cell carcinoma other imaging findings|Other Imaging Findings]] | [[Renal cell carcinoma other diagnostic studies|Other Diagnostic Studies]] |
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| ==Treatment== | | ==Treatment== |
| [[Kidney cancer medical therapy|Medical therapy]] | [[Kidney cancer surgery|Surgical options]] | [[Kidney cancer primary prevention|Primary prevention]] | [[Kidney cancer secondary prevention|Secondary prevention]] | [[Kidney cancer cost-effectiveness of therapy|Financial costs]] | [[Kidney cancer future or investigational therapies|Future therapies]] | | [[Renal cell carcinoma medical therapy|Medical Therapy]] | [[Renal cell carcinoma surgery|Surgery]] | [[Renal cell carcinoma primary prevention|Primary Prevention]] | [[Renal cell carcinoma cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Renal cell carcinoma future or investigational therapies|Future or Investigational Therapies]] |
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| ==Diagnostic Findings==
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| ===Pathology===
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| Gross examination shows a hypervascular lesion in the renal cortex, which is frequently multilobulated, yellow (because of the lipid accumulation) and calcified.
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| Light microscopy shows tumor cells forming cords, papillae, tubules or nests, and are atypical, polygonal and large. Because these cells accumulate [[glycogen]] and [[lipid]]s, their cytoplasm appear "clear", lipid-laden, the nuclei remain in the middle of the cells, and the cellular membrane is evident. Some cells may be smaller, with eosinophilic cytoplasm, resembling normal tubular cells. The stroma is reduced, but well vascularized. The tumor grows in large front, compressing the surrounding parenchyma, producing a pseudocapsule.<ref>http://www.pathologyatlas.ro/Renal%20Clear%20Cell%20Carcinoma.html</ref>
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| Secretion of vasoactive substances (e.g. [[renin]]) may cause [[arterial hypertension]], and release of [[erythropoietin]] may cause [[polycythemia]] (increased production of [[red blood cell]]s).
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| [[Image:Renal cell ca.jpg|thumb|left|350px|Renal cell carcinoma: This 8-centimeter carcinoma of the lower pole of the kidney shows extension beyond the cortical surface, but it does not infiltrate the perinephric adipose tissue. Microscopically, it is of the clear cell type.]] | | ==Case Studies== |
| <br clear="left"/>
| | [[Renal cell carcinoma case study one|Case #1]] |
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| ===Radiology=== | | ==Related Chapters== |
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| The characteristic appearance of renal cell carcinoma (RCC) is a solid renal lesion which disturbs the renal contour. It will frequently have an irregular or lobulated margin. 85% of solid renal masses will be RCC. 10% of RCC will contain calcifications, and some contain macroscopic fat (likely due to invasion and encasement of the perirenal fat). Following intravenous contrast administration ([[computed tomography]] or [[magnetic resonance imaging]]), enhancement will be noted, and will increase the conspicuity of the tumor relative to normal renal parenchyma.
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| '''Patient #1'''
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| [http://www.radswiki.net Images courtesy of RadsWiki]
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| [[Image:Renal cell carcinoma with intravascular extension 001.jpg|thumb|left|350px|T2: Renal cell carcinoma with intravascular extension]]
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| <br clear="left"/>
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| [[Image:Renal cell carcinoma with intravascular extension 002.jpg|thumb|left|350px|T1 post contrast: Renal cell carcinoma with intravascular extension]]
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| <br clear="left"/>
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| [[Image:Renal cell carcinoma with intravascular extension 003.jpg|thumb|left|350px|T1 post contrast: Renal cell carcinoma with intravascular extension]]
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| <br clear="left"/>
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| [[Image:Renal cell carcinoma with intravascular extension 004.jpg|thumb|left|350px|T1 post contrast: Renal cell carcinoma with intravascular extension]]
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| <br clear="left"/>
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| [[Image:Renal cell carcinoma with intravascular extension 005.jpg|thumb|left|350px|T1 post contrast: Renal cell carcinoma with intravascular extension]]
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| <br clear="left"/>
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| '''Patient #2'''
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| [http://www.radswiki.net Images courtesy of RadsWiki]
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| [[Image:Large renal cell carcinoma 001.jpg|thumb|left|350px|Large renal cell carcinoma]]
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| <br clear="left"/>
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| [[Image:Large renal cell carcinoma 002.jpg|thumb|left|350px|Large renal cell carcinoma]]
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| <br clear="left"/>
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| [[Image:Large renal cell carcinoma 003.jpg|thumb|left|350px|Large renal cell carcinoma]]
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| <br clear="left"/>
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| '''Patient #3'''
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| [http://www.radswiki.net Images courtesy of RadsWiki]
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| [[Image:Renal-cell-carcinoma-003.jpg|thumb|left|350px|Non contrast: Renal cell carcinoma]]
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| <br clear="left"/>
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| [[Image:Renal-cell-carcinoma-004.jpg|thumb|left|350px|Non contrast: Renal cell carcinoma]]
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| <br clear="left"/>
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| [[Image:Renal-cell-carcinoma-001.jpg|thumb|left|350px|Renal cell carcinoma]]
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| <br clear="left"/>
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| [[Image:Renal-cell-carcinoma-002.jpg|thumb|left|350px|Renal cell carcinoma]]
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| <br clear="left"/>
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| '''Patient #4'''
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| [http://www.radswiki.net Images courtesy of RadsWiki]
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| [[Image:Renal cell carcinoma 001.jpg|thumb|left|350px|Renal cell carcinoma]]
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| <br clear="left"/>
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| [[Image:Renal cell carcinoma 002.jpg|thumb|left|350px|Renal cell carcinoma]]
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| <br clear="left"/>
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| [[Image:Renal cell carcinoma 003.jpg|thumb|left|350px|Renal cell carcinoma]]
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| <br clear="left"/>
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| [[Image:Renal cell carcinoma 004.jpg|thumb|left|350px|Renal cell carcinoma]]
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| <br clear="left"/>
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| [[Image:Renal cell carcinoma 005.jpg|thumb|left|350px|Renal cell carcinoma]]
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| <br clear="left"/>
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| At diagnosis, 30% of renal cell carcinoma has spread to that kidney's renal vein, and 5-10% has continued on into the inferior vena cava<ref>Oto A, Herts BR, Remer EM, Novick AC. Inferior vena cava tumor thrombus in renal cell carcinoma: staging by MR imaging and impact on surgical treatment. AJR Am J Roentgenol. 1998 Dec;171(6):1619-24. PMID 9843299.</ref>.
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| Percutaneous biopsy can be performed by a [[radiologist]] using [[medical ultrasonography|ultrasound]] or [[computed tomography]] to guide sampling of the tumor for the purpose of diagnosis. However this is not routinely performed because when the typical imaging features of renal cell carcinoma are present, the possibility of an incorrectly negative result together with the risk of a medical complication to the patient make it unfavorable from a risk-benefit perspective.This is not completely accurate, there are new experimental treatments.
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| [[Image:RCC.jpg|thumb|left|350px|A [[computed axial tomography|CT scan]] showing bilateral renal cell carcinomas]]
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| <br clear="left"/>
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| ==Complications==
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| Patients with renal cell carcinoma are at risk of [[hepatic vein thrombosis]] aka/or [[Budd-Chiari syndrome]]
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| ==Treatment==
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| If the tumor is confined to the kidneys (occurs in about 40% of cases), then RCC can be treated roughly 90% of the time with [[surgery]]. If RCC has spread outside of the kidneys, often into the [[lymph nodes]] or the main vein of the kidney, then it is often treated with [[chemotherapy]] and other treatments.
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| ===Watchful waiting===
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| Small renal tumors represent the majority of tumors that are treated today by way of partial [[nephrectomy]]. The average growth of these masses is about 4-5 mm per year, and a significant proportion (up to 40%) of tumors less than 4cm in diameter are benign. 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%.
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| ===Surgery===
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| Surgical removal of all or part of the kidney ([[nephrectomy]]) is recommended. This may include removal of the [[adrenal gland]], retroperitoneal lymph nodes, and possibly tissues involved by direct extension (invasion) of the tumor into the surrounding tissues. In cases where the tumor has spread into the [[renal vein]], [[inferior vena cava]], and possibly the [[right atrium]] (angioinvasion), this portion of the tumor can be surgically removed, as well. In case of metastases surgical resection of the kidney ("cytoreductive nephrectomy") may improve survival<ref>Flanigan RC, Mickisch G, Sylvester R, Tangen C, Van Poppel H, Crawford ED. Cytoreductive nephrectomy in patients with metastatic renal cancer: a combined analysis. J Urol. 2004 Mar;171(3):1071-6. PMID 14767273.</ref>, as well as resection of a solitary metastatic lesion.
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| ===Percutaneous therapies===
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| [[Percutaneous]], image-guided therapies, usually managed by [[radiologists]], are being offered to patients with localized tumor, but who are not good candidates for a surgical procedure. This sort of procedure involves placing a probe through the skin and into the tumor using real-time imaging of both the probe tip and the tumor by [[computed tomography]], [[ultrasound]], or even [[magnetic resonance imaging]] guidance, and then destroying the tumor with heat ([[radiofrequency ablation]]) or cold ([[cryotherapy]]). These modalities are at a disadvantage compared to traditional surgery in that pathologic confirmation of complete tumor destruction is not possible.
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| ===Radiation therapy===
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| [[Radiation therapy]] is not commonly used for treatment of renal cell carcinoma because it is usually not successful. Radiation therapy may be used to palliate the symptoms of skeletal metastases.
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| ===Medications===
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| 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.<ref>{{cite journal |author=Michaelson MD, Iliopoulos O, McDermott DF, McGovern FJ, Harisinghani MG, Oliva E |title=Case records of the Massachusetts General Hospital. Case 17-2008. A 63-year-old man with metastatic renal-cell carcinoma |journal=N Engl J Med. |volume=358 |issue=22 |pages=2389–96 |year=2008 |month=May |pmid=18509125 |doi=10.1056/NEJMcpc0802449 |url=http://content.nejm.org/cgi/content/full/358/22/2389}}</ref>
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| [[Sorafenib]] was FDA approved in December 2005 for treatment of advanced renal cell cancer, the first receptor tyrosine [[kinase]] (RTK) inhibitor indicated for this use.
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| 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. [http://www.cancer.gov/Templates/drugdictionary.aspx?searchTxt=sunitinib][http://www.cancer.gov/Templates/drugdictionary.aspx?searchTxt=sorafenib]
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| Recently 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. <ref name=motzer>{{cite journal | author = Motzer RJ ''et al.'' | title = Sunitinib versus interferon alfa in metastatic renal-cell carcinoma | journal = [[New England Journal of Medicine|N Engl J Med]] | volume = 356 | issue = 2 | pages = 115–124 | year = 2007 | pmid = 17215529 | doi = 10.1056/NEJMoa065044}} </ref> Based on these results, lead investigator Dr. Robert Motzer announced at ASCO 2006 that “Sunitinib is the new reference standard for the first-line treatment of mRCC.” <ref name=motzer2>{{cite conference
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| |author=Motzer RJ ''et al.'' | title=Phase 3 Randomized Trial of Sunitinib malate (SU11248) versus Interferon-alfa as First-line Systemic Therapy for Patients with Metastatic Renal Cell Carcinoma |booktitle=ASCO 2006 |url=http://www.asco.org/portal/site/ASCO/menuitem.34d60f5624ba07fd506fe310ee37a01d/?vgnextoid=76f8201eb61a7010VgnVCM100000ed730ad1RCRD&vmview=abst_detail_view&confID=40&index=y&abstractID=30512}} </ref>
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| Temsirolimus (CCI-779) is an inhibitor of mTOR kinase (mamallian 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).
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| ===Chemotherapy===
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| [[Chemotherapy]] may be used in some cases, but cure is unlikely unless all the cancer can be removed with surgery. The use of Tyrosine Kinase (TK) inhibitors, such as [[Sunitinib]] and [[Sorafenib]], and [[Temsirolimus]] are described in a different section.
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| ===Vaccine===
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| In November 2006, it was announced that a [[vaccine]] had been developed and tested with very promising results.(See [http://www.dailymail.co.uk/pages/live/articles/news/news.html?in_article_id=416006&in_page_id=1770]) The new vaccine, called [[TroVax]], works by harnessing the patient's own immune system to fight the disease. Oxford BioMedica[http://www.oxfordbiomedica.co.uk/]. Further vaccine trials are underway.
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| ===Cryoablation===
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| This involves destroying the kidney tumor without surgery, by freezing the tumor. The process can remove 95% of tumors in one treatment and can be tolerated by patients who are not good candidates for surgery (older or weak patients). <ref> <http://www.yourcancertoday.com/news/drnakada.html" title=" Dr. Nakada, on Your Cancer Today</ref>.
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| The outcome varies depending on the size of the tumor, whether it is confined to the kidney or not, and the presence or absence of metastatic spread. The Fuhrman grading, which measures the aggressiveness of the tumor, may also affect survival, though the data is not as strong to support this.
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| The [[five year survival rate]] is around 90-95% for tumors less than 4 cm. For larger tumors confined to the kidney without venous invasion, survival is still relatively good at 80-85%. For tumors that extend through the renal capsule and out of the local fascial investments, the survivability reduces to near 60%. If it has metastasized to the lymph nodes, the 5-year survival is around 5 % to 15 %. If it has spread metastatically to other organs, the 5-year survival rate is less than 5 %.
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| For those that have tumor recurrence after surgery, the prognosis is generally poor. Renal cell carcinoma does not generally respond to chemotherapy or radiation. Immunotherapy, which attempts to induce the body to attack the remaining cancer cells, has shown promise. Recent trials are testing newer agents, though the current complete remission rate with these approaches are still low, around 12-20% in most series.
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| ==Prognosis==
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| The outcome varies depending on the size of the tumor, whether it is confined to the kidney or not, and the presence or absence of metastatic spread. The Furhman grading, which measures the aggressiveness of the tumor, may also affect survival, though the data is not as strong to support this.
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| The [[five year survival rate]] is around 90-95% for tumors less than 4 cm. For larger tumors confined to the kidney without venous invasion, survival is still relatively good at 80-85%. For tumors that extend through the renal capsule and out of the local fascial investments, the survivability reduces to near 60%. If it has metastasized to the lymph nodes, the 5-year survival is around 5 % to 15 %. If it has spread metastatically to other organs, the 5-year survival rate is less than 5 %.
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| For those that have tumor recurrence after surgery, the prognosis is generally poor. Renal cell carcinoma does not generally respond to [[chemotherapy]] or [[radiation]]. [[Immunotherapy]], which attempts to induce the body to attack the remaining cancer cells, has shown promise. Recent trials are testing newer agents, though the current complete remission rate with these approaches are still low, around 12-20% in most series.
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| ==See also==
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| *[[Stauffer syndrome]] | | *[[Stauffer syndrome]] |
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| ==External links==
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| *Photo at: [http://www.pathologyatlas.ro/Renal%20Clear%20Cell%20Carcinoma.html Atlas of Pathology]
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| *[http://www.411cancer.com/syndication/getMainNEW.jsp?type=TNPV&ctypeid=27&lid=1 ''www.411cancer.com''] - General Cancer Information
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| *[http://www.dailymail.co.uk/pages/live/articles/news/news.html?in_article_id=416006&in_page_id=1770 Vaccine for kidney cancer]
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| ==References==
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| {{reflist|2}}
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