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<div class="pre-content"><div><div class="bk_prnt"><p class="small">NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.</p><p>PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002-. </p></div><div class="iconblock clearfix whole_rhythm no_top_margin bk_noprnt"><a class="img_link icnblk_img" title="Table of Contents Page" href="/books/n/pdqcis/"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-pdqcis-lrg.png" alt="Cover of PDQ Cancer Information Summaries" height="100px" width="80px" /></a><div class="icnblk_cntnt eight_col"><h2>PDQ Cancer Information Summaries [Internet].</h2><a data-jig="ncbitoggler" href="#__NBK65815_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK65815_dtls__"><div>Bethesda (MD): <a href="http://www.cancer.gov/" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">National Cancer Institute (US)</a>; 2002-.</div></div><div class="half_rhythm"></div><div class="bk_noprnt"><form method="get" action="/books/n/pdqcis/" id="bk_srch"><div class="bk_search"><label for="bk_term" class="offscreen_noflow">Search term</label><input type="text" title="Search this book" id="bk_term" name="term" value="" data-jig="ncbiclearbutton" /> <input type="submit" class="jig-ncbibutton" value="Search this book" submit="false" style="padding: 0.1em 0.4em;" /></div></form></div></div></div></div></div>
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<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK65815_"><span class="title" itemprop="name">Renal Cell Cancer Treatment (PDQ®)</span></h1><div class="subtitle whole_rhythm">Health Professional Version</div><p class="contrib-group"><span itemprop="author">PDQ Adult Treatment Editorial Board</span>.</p><p class="small">Published online: October 1, 2015.</p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="_abs_rndgid_" itemprop="description"><p id="CDR0000062894__339">This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of renal cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.</p><p id="CDR0000062894__340">This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).</p></div><div id="CDR0000062894__1"><h2 id="_CDR0000062894__1_">General Information About Renal Cell Cancer</h2><div id="CDR0000062894__228"><h3>Incidence and Mortality</h3><p id="CDR0000062894__133">Estimated new cases and deaths from renal cell (kidney and renal pelvis) cancer in the United States in 2015:[<a class="bk_pop" href="#CDR0000062894_rl_1_1">1</a>]</p><ul id="CDR0000062894__134"><li class="half_rhythm"><div>New cases: 61,560.</div></li><li class="half_rhythm"><div>Deaths: 14,080.</div></li></ul></div><div id="CDR0000062894__304"><h3>Follow-up and Survivorship</h3><p id="CDR0000062894__2">Renal cell cancer, also called renal adenocarcinoma, or hypernephroma, can
|
|
often be cured if it is diagnosed and treated when still localized to the
|
|
kidney and to the immediately surrounding tissue. The probability of cure is
|
|
directly related to the stage or degree of tumor dissemination. Even when
|
|
regional lymphatics or blood vessels are involved with tumor, a significant
|
|
number of patients can achieve prolonged survival and probable cure.[<a class="bk_pop" href="#CDR0000062894_rl_1_2">2</a>] When
|
|
distant metastases are present, disease-free survival is poor; however,
|
|
occasional selected patients will survive after surgical resection of all known
|
|
tumor. Because a majority of patients are diagnosed when the tumor is still
|
|
relatively localized and amenable to surgical removal, approximately 73% of all
|
|
patients with renal cell cancer survive for 5 years.[<a class="bk_pop" href="#CDR0000062894_rl_1_3">3</a>] Occasionally, patients with locally
|
|
advanced or metastatic disease may exhibit indolent courses lasting several
|
|
years. Late tumor recurrence many years after initial treatment also occasionally
|
|
occurs.
|
|
</p><p id="CDR0000062894__3">Renal cell cancer is one of the few tumors in which well-documented cases of
|
|
spontaneous tumor regression in the absence of therapy exist, but this occurs
|
|
very rarely and may not lead to long-term survival. </p></div><div id="CDR0000062894__305"><h3>Treatment Modalities</h3><p id="CDR0000062894__306">Surgical resection is the
|
|
mainstay of treatment of this disease. Even in patients with disseminated
|
|
tumor, locoregional forms of therapy may play an important role in palliating
|
|
symptoms of the primary tumor or of ectopic hormone production. Systemic
|
|
therapy has demonstrated only limited effectiveness.
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</p></div><div id="CDR0000062894__274"><h3>Related Summaries</h3><p id="CDR0000062894__275">Other PDQ summaries containing information related to renal cell cancer include the following:</p><ul id="CDR0000062894__276"><li class="half_rhythm"><div><a href="/books/n/pdqcis/CDR0000574548/">Genetics of Kidney Cancer (Renal Cell Cancer)</a></div></li><li class="half_rhythm"><div><a href="/books/n/pdqcis/CDR0000062937/">Transitional Cell
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Cancer of the Renal Pelvis and Ureter Treatment</a></div></li><li class="half_rhythm"><div><a href="/books/n/pdqcis/CDR0000062789/">Wilms Tumor Treatment</a></div></li></ul></div><div id="CDR0000062894_rl_1"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062894_rl_1_1">American Cancer Society: Cancer Facts and Figures 2015. Atlanta, Ga: American Cancer Society, 2015. <a href="http://www.cancer.org/acs/groups/content/@editorial/documents/document/acspc-044552.pdf" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">Available online</a>. Last accessed October 30, 2015.</div></li><li><div class="bk_ref" id="CDR0000062894_rl_1_2">Sene AP, Hunt L, McMahon RF, et al.: Renal carcinoma in patients undergoing nephrectomy: analysis of survival and prognostic factors. Br J Urol 70 (2): 125-34, 1992. [<a href="https://pubmed.ncbi.nlm.nih.gov/1393433" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1393433</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062894_rl_1_3">National Cancer Institute: SEER Stat Fact Sheets: Kidney and Renal Pelvis Cancer. Bethesda, MD: National Cancer Institute, 2014. <a href="http://seer.cancer.gov/statfacts/html/kidrp.html" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">Available online</a>. Last accessed October 26, 2015.</div></li></ol></div></div><div id="CDR0000062894__5"><h2 id="_CDR0000062894__5_">Cellular Classification of Renal Cell Cancer</h2><p id="CDR0000062894__6">Approximately 85% of renal cell cancers are adenocarcinomas, and most of those are
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of proximal tubular origin. Most of the remainder are transitional cell
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carcinomas of the renal pelvis. (Refer to the PDQ summary on <a href="/books/n/pdqcis/CDR0000062937/">Transitional Cell
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Cancer of the Renal Pelvis and Ureter Treatment</a> for more information.)
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Adenocarcinomas may be separated into clear-cell and granular-cell carcinomas; however, the two cell types may occur together in some tumors. Some
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investigators have found that granular-cell tumors have a worse prognosis, but
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this finding is not universal. Distinguishing between well-differentiated
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renal adenocarcinomas and renal adenomas can be difficult. The diagnosis is
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usually made arbitrarily on the basis of size of the mass, but size alone
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should not influence the treatment approach, since metastases can occur with
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lesions as small as 0.5 centimeter.
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</p></div><div id="CDR0000062894__7"><h2 id="_CDR0000062894__7_">Stage Information for Renal Cell Cancer</h2><p id="CDR0000062894__8">The staging system for renal cell cancer is based on the degree of tumor spread
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beyond the kidney.[<a class="bk_pop" href="#CDR0000062894_rl_7_1">1</a>-<a class="bk_pop" href="#CDR0000062894_rl_7_3">3</a>] Involvement of blood vessels may not be a poor
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prognostic sign if the tumor is otherwise confined to the substance of the
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kidney. Abnormal liver function test results may be caused by a paraneoplastic
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syndrome that is reversible with tumor removal, and these types of results do not necessarily represent
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metastatic disease. Except when computed tomography (CT) examination is
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equivocal or when iodinated contrast material is contraindicated, CT scanning
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is as good as or better than magnetic resonance imaging for detecting
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renal masses.[<a class="bk_pop" href="#CDR0000062894_rl_7_4">4</a>]
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</p><div id="CDR0000062894__10"><h3>Definitions of TNM</h3><p id="CDR0000062894__227">The American Joint Committee on Cancer has designated staging by TNM
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classification to define renal cell cancer.[<a class="bk_pop" href="#CDR0000062894_rl_7_5">5</a>]</p><div id="CDR0000062894__222" class="table"><h3><span class="title">Table 1. Primary Tumor (T)<sup>a</sup></span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK65815.2/table/CDR0000062894__222/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000062894__222_lrgtbl__"><table class="no_margin"><tbody><tr><td colspan="1" rowspan="1" style="vertical-align:top;">TX</td><td colspan="1" rowspan="1" style="vertical-align:top;">Primary tumor cannot be assessed.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T0</td><td colspan="1" rowspan="1" style="vertical-align:top;">No evidence of primary tumor.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T1</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor ≤7 cm in greatest dimension, limited to the kidney.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T1a</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor ≤4 cm in greatest dimension, limited to the kidney.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T1b</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor >4 cm but not >7 cm in greatest dimension, limited to the kidney.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T2</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor >7 cm in greatest dimension, limited to the kidney.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T2a</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor >7 cm but ≤10 cm in greatest dimension, limited to the kidney.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T2b</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor >10 cm, limited to the kidney.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T3</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor extends into major veins or perinephric tissues but not into the ipsilateral adrenal gland and not beyond Gerota fascia.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T3a</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor grossly extends into the renal vein or its segmental (muscle containing) branches, or tumor invades perirenal and/or renal sinus fat but not beyond Gerota fascia.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T3b</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor grossly extends into the vena cava below the diaphragm.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T3c</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor grossly extends into the vena cava above the diaphragm or invades the wall of the vena cava.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T4</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor invades beyond Gerota fascia (including contiguous extension into the ipsilateral adrenal gland).</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin"><sup>a</sup>Reprinted with permission from AJCC: Kidney. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 479-89.</p></div></dd></dl></div></div></div><div id="CDR0000062894__291" class="table"><h3><span class="title">Table 2. Regional Lymph Nodes (N)<sup>a</sup></span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK65815.2/table/CDR0000062894__291/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000062894__291_lrgtbl__"><table class="no_margin"><tbody><tr><td colspan="1" rowspan="1" style="vertical-align:top;">NX</td><td colspan="1" rowspan="1" style="vertical-align:top;">Regional lymph nodes cannot be assessed.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">N0</td><td colspan="1" rowspan="1" style="vertical-align:top;">No regional lymph node metastasis.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">N1</td><td colspan="1" rowspan="1" style="vertical-align:top;">Metastases in regional lymph node(s).</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin"><sup>a</sup>Reprinted with permission from AJCC: Kidney. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 479-89.</p></div></dd></dl></div></div></div><div id="CDR0000062894__245" class="table"><h3><span class="title">Table 3. Distant Metastasis (M)<sup>a</sup></span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK65815.2/table/CDR0000062894__245/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000062894__245_lrgtbl__"><table class="no_margin"><tbody><tr><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td><td colspan="1" rowspan="1" style="vertical-align:top;">No distant metastasis.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">M1</td><td colspan="1" rowspan="1" style="vertical-align:top;">Distant metastasis.</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin"><sup>a</sup>Reprinted with permission from AJCC: Kidney. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 479-89.</p></div></dd></dl></div></div></div><div id="CDR0000062894__225" class="table"><h3><span class="title">Table 4. Anatomic Stage/Prognostic Groups<sup>a</sup></span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK65815.2/table/CDR0000062894__225/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000062894__225_lrgtbl__"><table class="no_margin"><thead><tr><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Stage</th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">T</th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">N</th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">M</th></tr></thead><tbody><tr><td colspan="1" rowspan="1" style="vertical-align:top;"> I</td><td colspan="1" rowspan="1" style="vertical-align:top;">T1</td><td colspan="1" rowspan="1" style="vertical-align:top;">N0</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"> II</td><td colspan="1" rowspan="1" style="vertical-align:top;">T2</td><td colspan="1" rowspan="1" style="vertical-align:top;">N0</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="2" style="vertical-align:top;"> III</td><td colspan="1" rowspan="1" style="vertical-align:top;">T1 or T2</td><td colspan="1" rowspan="1" style="vertical-align:top;">N1</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T3</td><td colspan="1" rowspan="1" style="vertical-align:top;">N0 or N1</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="2" style="vertical-align:top;"> IV</td><td colspan="1" rowspan="1" style="vertical-align:top;">T4</td><td colspan="1" rowspan="1" style="vertical-align:top;">Any N</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Any T</td><td colspan="1" rowspan="1" style="vertical-align:top;">Any N</td><td colspan="1" rowspan="1" style="vertical-align:top;">M1</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin"><sup>a</sup>Reprinted with permission from AJCC: Kidney. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 479-89.</p></div></dd></dl></div></div></div></div><div id="CDR0000062894_rl_7"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062894_rl_7_1">Bassil B, Dosoretz DE, Prout GR Jr: Validation of the tumor, nodes and metastasis classification of renal cell carcinoma. J Urol 134 (3): 450-4, 1985. [<a href="https://pubmed.ncbi.nlm.nih.gov/4032539" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 4032539</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062894_rl_7_2">Golimbu M, Joshi P, Sperber A, et al.: Renal cell carcinoma: survival and prognostic factors. Urology 27 (4): 291-301, 1986. [<a href="https://pubmed.ncbi.nlm.nih.gov/3962052" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3962052</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062894_rl_7_3">Robson CJ, Churchill BM, Anderson W: The results of radical nephrectomy for renal cell carcinoma. J Urol 101 (3): 297-301, 1969. [<a href="https://pubmed.ncbi.nlm.nih.gov/5765875" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 5765875</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062894_rl_7_4">Consensus conference. Magnetic resonance imaging. JAMA 259 (14): 2132-8, 1988. [<a href="https://pubmed.ncbi.nlm.nih.gov/3279242" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3279242</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062894_rl_7_5">Kidney. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 479-89.</div></li></ol></div></div><div id="CDR0000062894__31"><h2 id="_CDR0000062894__31_">Treatment Option Overview</h2><p id="CDR0000062894__32">Current treatment cures more than 50% of patients with
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stage I disease, but results in patients with stage IV disease are very poor. Thus,
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all patients with newly diagnosed renal cell cancer can appropriately be
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considered candidates for clinical trials, when possible.
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|
</p></div><div id="CDR0000062894__33"><h2 id="_CDR0000062894__33_">Stage I Renal Cell Cancer</h2><p id="CDR0000062894__246"><b>Stage I renal cell cancer is defined by the American Joint Committee on Cancer's TNM classification system:[<a class="bk_pop" href="#CDR0000062894_rl_33_1">1</a>]</b></p><ul id="CDR0000062894__247"><li class="half_rhythm"><div>T1, N0, M0</div></li></ul><p id="CDR0000062894__161">Surgical resection is the accepted, often curative, therapy for stage I renal
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|
cell cancer. Resection may be simple or radical. The latter operation
|
|
includes removal of the kidney, adrenal gland, perirenal fat, and Gerota
|
|
fascia, with or without a regional lymph node dissection. Some, but not all,
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surgeons believe the radical operation yields superior results. In patients
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|
who are not candidates for surgery, external-beam radiation therapy (EBRT) or arterial
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|
embolization can provide palliation. In patients with bilateral stage I
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neoplasms (concurrent or subsequent), bilateral partial nephrectomy or
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|
unilateral partial nephrectomy with contralateral radical nephrectomy, when
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|
technically feasible, may be a preferred alternative to bilateral nephrectomy
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|
with dialysis or transplantation.[<a class="bk_pop" href="#CDR0000062894_rl_33_2">2</a>] Increasing evidence suggests that a
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|
partial nephrectomy is curative in selected cases. A
|
|
pathologist should examine the gross specimen as well as the frozen section from the
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|
parenchymal margin of excision.[<a class="bk_pop" href="#CDR0000062894_rl_33_3">3</a>]</p><p id="CDR0000062894__162"><b>Standard treatment options:
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|
</b></p><ol id="CDR0000062894__163"><li class="half_rhythm"><div> Radical nephrectomy.[<a class="bk_pop" href="#CDR0000062894_rl_33_4">4</a>]</div></li><li class="half_rhythm"><div>Simple nephrectomy.[<a class="bk_pop" href="#CDR0000062894_rl_33_4">4</a>]</div></li><li class="half_rhythm"><div>Partial nephrectomy (selected patients).[<a class="bk_pop" href="#CDR0000062894_rl_33_2">2</a>,<a class="bk_pop" href="#CDR0000062894_rl_33_4">4</a>]</div></li><li class="half_rhythm"><div>EBRT (palliative).[<a class="bk_pop" href="#CDR0000062894_rl_33_4">4</a>]
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|
</div></li><li class="half_rhythm"><div>Arterial embolization (palliative).[<a class="bk_pop" href="#CDR0000062894_rl_33_4">4</a>,<a class="bk_pop" href="#CDR0000062894_rl_33_5">5</a>]</div></li><li class="half_rhythm"><div>Clinical trials. </div></li></ol><div id="CDR0000062894__TrialSearch_33_sid_5"><h3>Current Clinical Trials</h3><p id="CDR0000062894__TrialSearch_33_10">Check the list of NCI-supported cancer clinical trials that are now accepting patients with
|
|
<a href="http://www.cancer.gov/search/ClinicalTrialsLink.aspx?Diagnosis=43689&tt=1&format=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">stage I renal cell cancer</a>. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.</p><p id="CDR0000062894__TrialSearch_33_18">General information about clinical trials is also available from the <a href="http://www.cancer.gov/about-cancer/treatment/clinical-trials" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCI website</a>.</p></div><div id="CDR0000062894_rl_33"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062894_rl_33_1">Kidney. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 479-89.</div></li><li><div class="bk_ref" id="CDR0000062894_rl_33_2">Novick AC, Streem S, Montie JE, et al.: Conservative surgery for renal cell carcinoma: a single-center experience with 100 patients. J Urol 141 (4): 835-9, 1989. [<a href="https://pubmed.ncbi.nlm.nih.gov/2926874" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2926874</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062894_rl_33_3">Thrasher JB, Robertson JE, Paulson DF: Expanding indications for conservative renal surgery in renal cell carcinoma. Urology 43 (2): 160-8, 1994. [<a href="https://pubmed.ncbi.nlm.nih.gov/8116109" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8116109</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062894_rl_33_4">deKernion JB, Berry D: The diagnosis and treatment of renal cell carcinoma. Cancer 45 (7 Suppl): 1947-56, 1980. [<a href="https://pubmed.ncbi.nlm.nih.gov/6154520" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6154520</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062894_rl_33_5">Swanson DA, Wallace S, Johnson DE: The role of embolization and nephrectomy in the treatment of metastatic renal carcinoma. Urol Clin North Am 7 (3): 719-30, 1980. [<a href="https://pubmed.ncbi.nlm.nih.gov/7456183" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7456183</span></a>]</div></li></ol></div></div><div id="CDR0000062894__43"><h2 id="_CDR0000062894__43_">Stage II Renal Cell Cancer</h2><p id="CDR0000062894__248"><b>Stage II renal cell cancer is defined by the American Joint Committee on Cancer's TNM classification system:[<a class="bk_pop" href="#CDR0000062894_rl_43_1">1</a>]</b></p><ul id="CDR0000062894__249"><li class="half_rhythm"><div>T2, N0, M0</div></li></ul><p id="CDR0000062894__165">Radical resection is the accepted, often curative, therapy for stage II renal
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|
cell cancer. The operation includes removal of
|
|
the kidney, adrenal gland, perirenal fat, and Gerota fascia, with or without
|
|
a regional lymph node dissection.[<a class="bk_pop" href="#CDR0000062894_rl_43_2">2</a>] Lymphadenectomy is commonly employed, but
|
|
its effectiveness has not been definitively proven. External-beam radiation therapy
|
|
(EBRT) has been given before or after nephrectomy without conclusive evidence that
|
|
this improves survival when compared with the results of surgery alone; however, it may be of
|
|
benefit in selected patients with more extensive tumors. In patients who are
|
|
not candidates for surgery, arterial embolization can provide palliation.
|
|
</p><p id="CDR0000062894__166"><b>Standard treatment options:
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|
</b></p><ol id="CDR0000062894__167"><li class="half_rhythm"><div>Radical nephrectomy.[<a class="bk_pop" href="#CDR0000062894_rl_43_3">3</a>]</div></li><li class="half_rhythm"><div> Nephrectomy before or after EBRT (selected
|
|
patients).[<a class="bk_pop" href="#CDR0000062894_rl_43_3">3</a>]</div></li><li class="half_rhythm"><div> Partial nephrectomy (selected patients).[<a class="bk_pop" href="#CDR0000062894_rl_43_3">3</a>]</div></li><li class="half_rhythm"><div>EBRT (palliative).[<a class="bk_pop" href="#CDR0000062894_rl_43_3">3</a>]
|
|
</div></li><li class="half_rhythm"><div>Arterial embolization (palliative).</div></li><li class="half_rhythm"><div>Clinical trials. </div></li></ol><div id="CDR0000062894__TrialSearch_43_sid_6"><h3>Current Clinical Trials</h3><p id="CDR0000062894__TrialSearch_43_10">Check the list of NCI-supported cancer clinical trials that are now accepting patients with
|
|
<a href="http://www.cancer.gov/search/ClinicalTrialsLink.aspx?Diagnosis=43690&tt=1&format=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">stage II renal cell cancer</a>. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.</p><p id="CDR0000062894__TrialSearch_43_18">General information about clinical trials is also available from the <a href="http://www.cancer.gov/about-cancer/treatment/clinical-trials" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCI website</a>.</p></div><div id="CDR0000062894_rl_43"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062894_rl_43_1">Kidney. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 479-89.</div></li><li><div class="bk_ref" id="CDR0000062894_rl_43_2">Phillips E, Messing EM: Role of lymphadenectomy in the treatment of renal cell carcinoma. Urology 41 (1): 9-15, 1993. [<a href="https://pubmed.ncbi.nlm.nih.gov/8420090" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8420090</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062894_rl_43_3">deKernion JB, Berry D: The diagnosis and treatment of renal cell carcinoma. Cancer 45 (7 Suppl): 1947-56, 1980. [<a href="https://pubmed.ncbi.nlm.nih.gov/6154520" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6154520</span></a>]</div></li></ol></div></div><div id="CDR0000062894__53"><h2 id="_CDR0000062894__53_">Stage III Renal Cell Cancer</h2><p id="CDR0000062894__250"><b>Stage III renal cell cancer is defined by the American Joint Committee on Cancer's TNM classification system:[<a class="bk_pop" href="#CDR0000062894_rl_53_1">1</a>]</b></p><ul id="CDR0000062894__251"><li class="half_rhythm"><div>T1 or T2, N1, M0</div></li><li class="half_rhythm"><div>T3, N0 or N1, M0</div></li></ul><p id="CDR0000062894__170"><b><div class="milestone-start" id="CDR0000062894__169"></div>Treatment information for patients whose disease has the following classification: </b></p><ul id="CDR0000062894__171"><li class="half_rhythm"><div>T3a, N0, M0</div></li></ul><p id="CDR0000062894__172">Radical resection is the accepted, often curative, therapy for stage III renal
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cell cancer. The operation includes removal of
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the kidney, adrenal gland, perirenal fat, and Gerota fascia, with or without
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a regional lymph node dissection.[<a class="bk_pop" href="#CDR0000062894_rl_53_2">2</a>] Lymphadenectomy is commonly employed, but
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its effectiveness has not been definitively proven. External-beam radiation
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therapy (EBRT) has been given before or after nephrectomy without conclusive evidence that
|
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this improves survival when compared with the results of surgery alone; however, it may be of
|
|
benefit in selected patients with more extensive tumors. In patients who are
|
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not candidates for surgery, arterial embolization can provide palliation. In
|
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patients with bilateral stage T3a neoplasms (concurrent or subsequent),
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bilateral partial nephrectomy or unilateral partial nephrectomy with
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contralateral radical nephrectomy, when technically feasible, may be a preferred
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alternative to bilateral nephrectomy with dialysis or transplantation.<div class="milestone-end"></div>[<a class="bk_pop" href="#CDR0000062894_rl_53_3">3</a>]</p><p id="CDR0000062894__112"><b><div class="milestone-start" id="CDR0000062894__54"></div>Treatment information for patients whose disease has the following classification:</b></p><ul id="CDR0000062894__113"><li class="half_rhythm"><div>T3b, N0, M0</div></li></ul><p id="CDR0000062894__56">Radical resection is the accepted, often curative, therapy for this stage of
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renal cell cancer. The operation includes
|
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removal of the kidney, adrenal gland, perirenal fat, and Gerota fascia, with
|
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or without a regional lymph node dissection. Lymphadenectomy is commonly
|
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employed, but its effectiveness has not been definitively proven. Surgery is
|
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extended to remove the entire renal vein and caval thrombus and a portion of
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the vena cava as necessary.[<a class="bk_pop" href="#CDR0000062894_rl_53_4">4</a>] EBRT has been given before
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or after nephrectomy without conclusive evidence that this improves survival when compared with the results of surgery alone; however, it may be of benefit in selected
|
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patients with more extensive tumors. In patients who are not candidates for
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surgery, arterial embolization can provide palliation. In patients with stage
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T3b neoplasms who manifest concurrent or subsequent renal cell carcinoma in the
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contralateral kidney, a partial nephrectomy, when technically feasible, may be a
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preferred alternative to bilateral nephrectomy with dialysis or
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transplantation.<div class="milestone-end"></div>[<a class="bk_pop" href="#CDR0000062894_rl_53_3">3</a>,<a class="bk_pop" href="#CDR0000062894_rl_53_5">5</a>,<a class="bk_pop" href="#CDR0000062894_rl_53_6">6</a>]
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</p><p id="CDR0000062894__99"><b><div class="milestone-start" id="CDR0000062894__57"></div>Treatment information for patients whose disease has the following classifications:</b></p><ul id="CDR0000062894__114"><li class="half_rhythm"><div>T1, N1, M0</div></li><li class="half_rhythm"><div>T2, N1, M0</div></li><li class="half_rhythm"><div>T3, N1, M0</div></li><li class="half_rhythm"><div>T3a, N1, M0</div></li><li class="half_rhythm"><div>T3b, N1, M0</div></li><li class="half_rhythm"><div>T3c, N1, M0</div></li></ul><p id="CDR0000062894__58">This stage of renal cell cancer is curable with surgery in a small minority of
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cases. A radical nephrectomy and lymph node dissection is necessary. The
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value of preoperative and postoperative EBRT has not been
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demonstrated, but EBRT may be used for palliation in
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patients who are not candidates for surgery. Arterial embolization of the
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tumor with gelfoam or other materials may be employed preoperatively to reduce
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blood loss at nephrectomy or for palliation in patients with inoperable
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disease.
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<div class="milestone-end"></div></p><p id="CDR0000062894__173"><b>Standard treatment options:
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</b></p><ol id="CDR0000062894__174"><li class="half_rhythm"><div>Radical nephrectomy with renal vein and, as necessary, vena
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caval resection (for T3b tumors).[<a class="bk_pop" href="#CDR0000062894_rl_53_4">4</a>] Radical nephrectomy with lymph
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node dissection.</div></li><li class="half_rhythm"><div>Preoperative embolization and radical nephrectomy.[<a class="bk_pop" href="#CDR0000062894_rl_53_7">7</a>,<a class="bk_pop" href="#CDR0000062894_rl_53_8">8</a>]
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</div></li><li class="half_rhythm"><div>EBRT (palliative).[<a class="bk_pop" href="#CDR0000062894_rl_53_7">7</a>]</div></li><li class="half_rhythm"><div>Tumor embolization (palliative).[<a class="bk_pop" href="#CDR0000062894_rl_53_8">8</a>]
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</div></li><li class="half_rhythm"><div> Palliative nephrectomy.
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</div></li><li class="half_rhythm"><div> Preoperative or postoperative EBRT and radical nephrectomy.[<a class="bk_pop" href="#CDR0000062894_rl_53_7">7</a>]</div></li><li class="half_rhythm"><div> Clinical trials involving adjuvant interferon-alpha.
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</div></li></ol><div id="CDR0000062894__TrialSearch_53_sid_7"><h3>Current Clinical Trials</h3><p id="CDR0000062894__TrialSearch_53_10">Check the list of NCI-supported cancer clinical trials that are now accepting patients with
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<a href="http://www.cancer.gov/search/ClinicalTrialsLink.aspx?Diagnosis=43691&tt=1&format=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">stage III renal cell cancer</a>. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.</p><p id="CDR0000062894__TrialSearch_53_18">General information about clinical trials is also available from the <a href="http://www.cancer.gov/about-cancer/treatment/clinical-trials" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCI website</a>.</p></div><div id="CDR0000062894_rl_53"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062894_rl_53_1">Kidney. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 479-89.</div></li><li><div class="bk_ref" id="CDR0000062894_rl_53_2">Phillips E, Messing EM: Role of lymphadenectomy in the treatment of renal cell carcinoma. Urology 41 (1): 9-15, 1993. [<a href="https://pubmed.ncbi.nlm.nih.gov/8420090" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8420090</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062894_rl_53_3">Novick AC, Streem S, Montie JE, et al.: Conservative surgery for renal cell carcinoma: a single-center experience with 100 patients. J Urol 141 (4): 835-9, 1989. [<a href="https://pubmed.ncbi.nlm.nih.gov/2926874" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2926874</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062894_rl_53_4">Hatcher PA, Anderson EE, Paulson DF, et al.: Surgical management and prognosis of renal cell carcinoma invading the vena cava. J Urol 145 (1): 20-3; discussion 23-4, 1991. [<a href="https://pubmed.ncbi.nlm.nih.gov/1984092" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1984092</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062894_rl_53_5">deKernion JB: Management of renal adenocarcinoma. In: deKernion JB, Paulson DF, eds.: Genitourinary Cancer Management. Philadelphia, Pa: Lea and Febiger, 1987, pp 187-217.</div></li><li><div class="bk_ref" id="CDR0000062894_rl_53_6">Angermeier KW, Novick AC, Streem SB, et al.: Nephron-sparing surgery for renal cell carcinoma with venous involvement. J Urol 144 (6): 1352-5, 1990. [<a href="https://pubmed.ncbi.nlm.nih.gov/2231924" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2231924</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062894_rl_53_7">deKernion JB, Berry D: The diagnosis and treatment of renal cell carcinoma. Cancer 45 (7 Suppl): 1947-56, 1980. [<a href="https://pubmed.ncbi.nlm.nih.gov/6154520" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6154520</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062894_rl_53_8">Swanson DA, Wallace S, Johnson DE: The role of embolization and nephrectomy in the treatment of metastatic renal carcinoma. Urol Clin North Am 7 (3): 719-30, 1980. [<a href="https://pubmed.ncbi.nlm.nih.gov/7456183" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7456183</span></a>]</div></li></ol></div></div><div id="CDR0000062894__67"><h2 id="_CDR0000062894__67_">Stage IV and Recurrent Renal Cell Cancer</h2><p id="CDR0000062894__252"><b>Stage IV renal cell cancer is defined by the American Joint Committee on Cancer's TNM classification system:[<a class="bk_pop" href="#CDR0000062894_rl_67_1">1</a>]</b></p><ul id="CDR0000062894__253"><li class="half_rhythm"><div>T4, any N, M0</div></li><li class="half_rhythm"><div>Any T, any N, M1</div></li></ul><p id="CDR0000062894__176">The prognosis for any treated renal cell cancer patient with progressing,
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recurring, or relapsing disease is poor, regardless of cell type or stage. Almost all patients with stage IV renal cell cancer are incurable. The
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question and selection of further treatment depends on many factors, including
|
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previous treatment and site of recurrence, as well as individual patient
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|
considerations. Carefully selected patients may benefit from surgical
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resection of localized metastatic disease, particularly if they have had a prolonged, disease-free interval since their primary therapy.
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</p><div id="CDR0000062894__177"><h3>Local Therapy</h3><p id="CDR0000062894__214">Tumor embolization, external-beam
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radiation therapy (EBRT), and nephrectomy can aid in the palliation of symptoms caused by the
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|
primary tumor or related ectopic hormone or cytokine production. For patients with metastatic disease, two randomized studies have demonstrated an overall survival (OS) benefit in selected patients who have undergone initial cytoreductive nephrectomy prior to the administration of interferon-alpha.[<a class="bk_pop" href="#CDR0000062894_rl_67_2">2</a>,<a class="bk_pop" href="#CDR0000062894_rl_67_3">3</a>] </p><p id="CDR0000062894__265">In the larger study, 246 patients were randomly assigned to either undergo a nephrectomy followed by interferon-alpha or receive interferon-alpha alone.[<a class="bk_pop" href="#CDR0000062894_rl_67_2">2</a>] The median OS was 11.1 months when the primary tumor was removed first (95% confidence interval [CI], 9.2–16.5) compared with 8.1 months in the control arm (95% CI, 5.4–9.5; <i>P</i> = .05). In the smaller study, 85 patients with identical eligibility criteria were randomly assigned to treatment as in the larger study.[<a class="bk_pop" href="#CDR0000062894_rl_67_3">3</a>] Patients who underwent nephrectomy before receiving interferon-alpha had a median OS of 17 months compared with an OS of 7 months in patients who received interferon-alpha alone (hazard ratio [HR], 0.54; 95% CI, 0.31–0.94; <i>P</i> = .03).</p><p id="CDR0000062894__266">These studies were restricted to patients who were asymptomatic or minimally symptomatic, with a performance status (PS) of zero or one, according to the Eastern Cooperative Oncology Group (ECOG) rating scale; these patients were also considered to be candidates for postoperative immunotherapy.[<a class="bk_pop" href="#CDR0000062894_rl_67_2">2</a>,<a class="bk_pop" href="#CDR0000062894_rl_67_3">3</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>] Whether the benefit of cytoreductive nephrectomy extends to patients who are not subsequently treated with interferon-alpha has not been tested.</p><p id="CDR0000062894__178"> Selected patients with solitary or a limited number of
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|
distant metastases can achieve prolonged survival with nephrectomy and surgical
|
|
resection of the metastases.[<a class="bk_pop" href="#CDR0000062894_rl_67_4">4</a>-<a class="bk_pop" href="#CDR0000062894_rl_67_9">9</a>] Even patients with brain metastases had similar results.[<a class="bk_pop" href="#CDR0000062894_rl_67_10">10</a>] The likelihood of achieving therapeutic
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|
benefit with this approach appears enhanced in patients with a long
|
|
disease-free interval between the initial nephrectomy and the development of
|
|
metastatic disease.
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|
</p></div><div id="CDR0000062894__179"><h3>Cytokine Therapy</h3><p id="CDR0000062894__180">Cytokine therapy with interferon-alpha or interleukin-2 (IL-2) has been shown to induce objective responses, and interferon-alpha appears to have a modest impact on survival in selected patients. Interferon-alpha has approximately a 15%
|
|
objective response rate in appropriately selected individuals.[<a class="bk_pop" href="#CDR0000062894_rl_67_11">11</a>] In
|
|
general, these patients have nonbulky pulmonary and/or soft tissue metastases
|
|
with excellent PS ratings of zero or one, according to the ECOG rating scale, and the patients show no weight loss. The
|
|
interferon-alpha doses used in studies reporting good response rates have been
|
|
in an intermediate range (6–20 million units 3 times weekly). A Cochrane analysis of six randomized trials, with a total of 963 patients, indicated an HR for survival of 0.78 (CI, 0.67–0.90) or a weighted average improvement in survival of 2.6 months.[<a class="bk_pop" href="#CDR0000062894_rl_67_11">11</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>] </p><p id="CDR0000062894__182">High-dose IL-2 produces a similar overall response rate to interferon-alpha, but approximately 5% of patients had durable complete remissions.[<a class="bk_pop" href="#CDR0000062894_rl_67_12">12</a>-<a class="bk_pop" href="#CDR0000062894_rl_67_17">17</a>] IL-2 has never been shown in a randomized, controlled trial to result in longer survival. High-dose IL-2 is used because it is the only systemic therapy that has been associated with inducing durable complete remissions, albeit in a small fraction (about 5%) of patients who are eligible for this treatment. The optimum dose of IL-2 is unknown. High-dose
|
|
therapy appears to be associated with higher response rates but with more toxic
|
|
effects. Low-dose inpatient regimens have activity against renal cell carcinoma with fewer toxic
|
|
effects, especially hypotension, but have not been shown to be superior to placebo or any alternative regimen with regard to survival or quality of life.[<a class="bk_pop" href="#CDR0000062894_rl_67_18">18</a>] Outpatient subcutaneous administration
|
|
has also demonstrated responses with acceptable toxic effects but, again, with unclear survival or quality of life benefit.[<a class="bk_pop" href="#CDR0000062894_rl_67_19">19</a>] Combinations of IL-2 and
|
|
interferon-alpha have been studied, but outcomes have not been better with
|
|
high-dose or low-dose IL-2 alone.[<a class="bk_pop" href="#CDR0000062894_rl_67_20">20</a>,<a class="bk_pop" href="#CDR0000062894_rl_67_21">21</a>]</p></div><div id="CDR0000062894__183"><h3>Antiangiogenic and Other Targeted Therapy</h3><p id="CDR0000062894__267">A growing understanding of the biology of cancer in general, and renal cell carcinoma in particular, has led to the development and U.S. Food and Drug Administration (FDA) approval of six new agents that target specific growth pathways. Two of the approved targeted therapies block the mammalian target of rapamycin (mTOR), a serine/threonine protein kinase that regulates cell growth, division, and survival. </p><div id="CDR0000062894__309"><h4>Temsirolimus</h4><p id="CDR0000062894__310">Temsirolimus, an intravenously administered mTOR inhibitor, was shown to result in prolonged OS compared with interferon-alpha in a phase III randomized controlled trial that enrolled intermediate- and poor-risk patients. The trial enrolled patients with a variety of subtypes of renal cell carcinoma and was not restricted to clear-cell kidney cancer. The HR for death was 0.73 (95% CI, 0.58–0.92, <i>P</i> = .008), making temsirolimus the only therapy for renal cell carcinoma to have clearly been shown to result in longer OS than interferon-alpha using conventional statistical analysis.[<a class="bk_pop" href="#CDR0000062894_rl_67_22">22</a>]</p></div><div id="CDR0000062894__311"><h4>Everolimus</h4><p id="CDR0000062894__312">Everolimus is an orally administered mTOR inhibitor that was evaluated in a double-blind, randomized, placebo-controlled phase III trial. The trial enrolled patients with metastatic renal cell carcinoma with a clear-cell component that had progressed during or within 6 months of stopping treatment with sunitinib or sorafenib, or both drugs. Median progression-free survival (PFS) was 4.0 months with everolimus compared with 1.9 months with placebo.[<a class="bk_pop" href="#CDR0000062894_rl_67_23">23</a>] No difference in OS was reported.</p></div><div id="CDR0000062894__313"><h4>Anti-VEGF</h4><p id="CDR0000062894__314">Based on research showing that most clear-cell renal cell carcinomas carried a mutation resulting in constitutive production of cytokines stimulating angiogenesis, several agents that targeted vascular endothelial growth factor (VEGF)-mediated pathways were developed. Several of these agents have been shown in randomized, controlled trials to significantly delay progression of clear-cell renal cell carcinoma, but none has resulted in a statistically significant increase in OS as conventionally assessed. Many of these trials allowed crossover upon progression and, in some instances, other agents with similar biological activity were available to patients after they withdrew from the clinical trial. These facts may have made it more difficult to detect an OS benefit. For the clinician, this makes it challenging to determine the real benefit of these drugs to the patient. The four FDA-approved anti-VEGF agents include three oral tyrosine kinase inhibitors: pazopanib, sorafenib, and sunitinib; and an anti-VEGF monoclonal antibody, bevacizumab. Axitinib is a newer, highly selective, and more potent inhibitor of VEGF receptors 1, 2, and 3 and has been approved by the FDA for the treatment of advanced renal cell carcinoma after the failure of one previously received systemic therapy.[<a class="bk_pop" href="#CDR0000062894_rl_67_24">24</a>]</p></div><div id="CDR0000062894__315"><h4>Sunitinib</h4><p id="CDR0000062894__316">Sunitinib and the combination of bevacizumab plus interferon-alpha have each been associated with longer PFS than interferon-alpha alone in randomized, controlled trials. Sunitinib is an orally available multikinase inhibitor (VEGFR-1, VEGFR-2, PDGFR, c-Kit). In 750 previously untreated patients, all of whom had clear-cell kidney cancer, a phase III trial compared sunitinib with interferon-alpha.[<a class="bk_pop" href="#CDR0000062894_rl_67_25">25</a>] Sunitinib as first-line systemic therapy was associated with a median PFS of 11 months compared with 5 months for interferon-alpha. The HR for progression was 0.42 (95% CI, 0.32–0.54; <i>P</i> < .001).[<a class="bk_pop" href="#CDR0000062894_rl_67_25">25</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335131/" class="def">Level of evidence: 1iiDiii</a>] However, the analysis for OS showed a strong but statistically nonsignificant trend to improved survival (26.4 months vs. 21.8 months, HR, 0.82; 95% CI, 0.669–1.001; <i>P</i> = .051).[<a class="bk_pop" href="#CDR0000062894_rl_67_26">26</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335131/" class="def">Level of evidence: 1iiDiii</a>] Bevacizumab, a monoclonal antibody that binds to and neutralizes circulating VEGF protein, delayed progression of clear-cell renal cell carcinoma when compared with placebo in patients with disease refractory to biological therapy.[<a class="bk_pop" href="#CDR0000062894_rl_67_27">27</a>] Similarly, bevacizumab plus interferon-alpha as first-line therapy resulted in longer PFS but not OS compared with interferon alpha alone in two similarly designed, randomized, controlled trials.[<a class="bk_pop" href="#CDR0000062894_rl_67_28">28</a>,<a class="bk_pop" href="#CDR0000062894_rl_67_29">29</a>]</p></div><div id="CDR0000062894__317"><h4>Axitinib</h4><p id="CDR0000062894__318">Axitinib was shown to prolong progression of disease when used as second-line systemic therapy. A randomized, controlled trial of 723 patients conducted at 175 sites in 22 countries evaluated axitinib versus sorafenib as treatment for renal cell carcinoma with a clear-cell component that had progressed during or after first-line treatment with sunitinib (54%), cytokines (35%), bevacizumab plus interferon (8%), or temsirolimus (3%).[<a class="bk_pop" href="#CDR0000062894_rl_67_24">24</a>,<a class="bk_pop" href="#CDR0000062894_rl_67_30">30</a>] The primary endpoint was PFS, and the data were analyzed when disease in 88% of the axitinib patients and 90% of the sorafenib patients had progressed, while 58% and 59%, respectively, had died. </p><p id="CDR0000062894__319">Median PFS was 8.3 months for axitinib and 5.7 months for sorafenib (HR, 0.656; 95% CI, 0.552–0.779, <i>P</i> < .0001 for progression<sub> death</sub> using a one-sided log-rank test and a threshold of <i>P </i> < .025 for significance). Median OS was 20.1 months with axitinib compared with 19.2 months with sorafenib (HR, 0.969; 95% CI, 0.80–1.17, <i>P</i> = .374). However, the largest benefit was seen in patients who received cytokines as first-line therapy and whose median PFS was 12.2 months with axitinib compared with 8.2 months with sorafenib (<i>P</i> < .0001), while median OS was 29.4 months with axitinib compared with 27.8 months with sorafenib (HR, 0.81; 95% CI, 0.5501.19; <i>P</i> = .144). In contrast, in patients who had previously received sunitinib, axitinib was associated with a 2.1-month increase in PFS compared with sorafenib (6.5 months vs. 4.4 months, one-sided <i>P</i> = .002), but median OS was nearly identical: 15.2 months with axitinib compared with 16.5 months with sorafenib (HR, 1.0; 95% CI, 0.782–1.270; <i>P</i> = .49).[<a class="bk_pop" href="#CDR0000062894_rl_67_30">30</a>]</p><p id="CDR0000062894__320">Comparing the toxicity of the axitinib and sorafenib regimens is complicated because the axitinib arm included a dose-escalation component, and only those patients who tolerated the lower dose were subsequently given the higher doses. Hypertension, nausea, dysphonia, and hypothyroidism were more common with axitinib, whereas palmar-plantar erythrodysesthesia, alopecia, and rash were more common with sorafenib.[<a class="bk_pop" href="#CDR0000062894_rl_67_24">24</a>,<a class="bk_pop" href="#CDR0000062894_rl_67_30">30</a>]</p></div><div id="CDR0000062894__321"><h4>Pazopanib</h4><p id="CDR0000062894__322">Pazopanib is an orally available multikinase inhibitor (VEGFR-1, VEGFR-2, VEGFR-3, PDGFR, and c-KIT) and has also been approved for the treatment of patients with advanced renal cell carcinoma.[<a class="bk_pop" href="#CDR0000062894_rl_67_31">31</a>]</p><p id="CDR0000062894__323">Pazopanib was evaluated in a randomized, placebo-controlled, international trial (<a href="http://cancer.gov/clinicaltrials/search/view?version=healthprofessional&cdrid=490122" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">VEG015192</a> [<a href="https://clinicaltrials.gov/show/NCT00334282" title="Study NCT00334282" ref="pagearea=body&targetsite=external&targetcat=link&targettype=clinical-trial">NCT00334282</a>]) that enrolled 435 patients with clear-cell or predominantly clear-cell renal cell carcinoma.[<a class="bk_pop" href="#CDR0000062894_rl_67_32">32</a>] Nearly 50% of the patients had previously received cytokine therapy, although the remainder of them were treatment naïve. PFS was significantly prolonged in the pazopanib arm at 9.2 months compared with 4.2 months in the placebo arm. The HR for progression was 0.46 (95% CI, 0.34–0.62; <i>P</i> < .0001), and the median duration of response was longer than 1 year. </p><p id="CDR0000062894__324">Pazopanib was also compared with sunitinib in a randomized, controlled trial (<a href="http://cancer.gov/clinicaltrials/search/view?version=healthprofessional&cdrid=601947" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCT00720941</a>) that enrolled 1,110 patients who had metastatic renal cell carcinoma with a clear-cell component in a 1:1 ratio.[<a class="bk_pop" href="#CDR0000062894_rl_67_33">33</a>] The primary endpoint was PFS. The study was powered to assess the noninferiority of pazopanib. Results were reported when there was disease progression in 336 of 557patients (60%) who received pazopanib and 323 of 553 patients (58%) who received sunitinib. The median PFS time was 8.4 months for those in the pazopanib arm and 9.5 months for those in the sunitinib arm (HR, 1.05; CI, .9–1.22). There was no difference in OS (HR, 0.91; 95% CI, .76–1.08). Although quality of life was compared in the study, differences in the scheduled administration of the medications made this comparison difficult to interpret. </p><p id="CDR0000062894__331">A subsequent double-blind, randomized, controlled, cross-over trial compared sunitinib followed by pazopanib with pazopanib followed by sunitinib, and the primary endpoint was patient preference for one drug over the other.[<a class="bk_pop" href="#CDR0000062894_rl_67_34">34</a>] Patients were treated for 10 weeks with either sunitinib or pazopanib, followed by a 2-week washout period, followed by 10 more weeks of treatment with the other drug. Preference was assessed at the end of the second 10-week–treatment period. This study design created possible bias in favor of pazopanib. </p><p id="CDR0000062894__332">Although the typical regimen for administering sunitinib is a 6-week cycle of 4 weeks on the drug and 2 weeks off the drug, the Patient Preference Study of Pazopanib Versus Sunitinib in Advanced or Metastatic Kidney Cancer (<a href="http://cancer.gov/clinicaltrials/search/view?version=healthprofessional&cdrid=665885" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PISCES</a> [<a href="https://clinicaltrials.gov/show/NCT01064310" title="Study NCT01064310" ref="pagearea=body&targetsite=external&targetcat=link&targettype=clinical-trial">NCT01064310</a>]) chose a treatment period of 10 weeks rather than 12 weeks. Because of this treatment-period change, the 10 weeks of sunitinib treatment included 4 weeks on the drug, followed by 2 weeks off the drug, followed by 4 more weeks on the drug. Patients assigned to pazopanib followed by sunitinib had their preference for treatment assessed at the end of the second 4-weeks-on-the-drug period during which the patients took sunitinib daily for 28 days. At that point, the sunitinib side effects became the most severe. The expected result from an assessment conducted at the end of a 6-week treatment cycle versus the 4-week treatment cycle would be greatly abated side effects. </p><p id="CDR0000062894__333"> In addition, the 2-week washout period that occurred between the two 10-week treatment periods was a true break from treatment for patients assigned to take pazopanib first; however, for the patients taking sunitinib, the 2-week washout period was actually just the completion of their second 6-week treatment cycle. In other words, patients assigned to pazopanib first had a true 2-week break from treatment, and their drug preference was assessed at the peak period of toxic effects from sunitinib; however, the patients assigned to sunitinib first had no true treatment break before starting pazopanib and may have had less opportunity to recover from the side effects of sunitinib.</p><p id="CDR0000062894__334">Despite these limitations, 70% of the patients preferred pazopanib, and 22% of the patients preferred sunitinib (<i>P</i> < .001). More patients preferred pazopanib regardless of the treatment they received first; however, that difference was greater for the patients who received pazopanib first (80% vs. 11%) compared with the patients who received sunitinib first (62% vs. 32%). The main side effects cited by the patients that contributed to patient preference were diarrhea, health-related quality of life, fatigue, loss of appetite, taste changes, nausea and vomiting, hand and foot soreness, stomach pain, and mouth and throat soreness. The patients preferring pazopanib cited less fatigue and better overall quality of life as the most common reasons for their preference. The patients preferring sunitinib cited less diarrhea and better quality of life as the most common reasons for their preference. Physician preference was a secondary endpoint of the study, and 61% of physicians preferred to continue patient treatment with pazopanib, compared with 22% of physicians who preferred to continue patient treatment with sunitinib. </p></div><div id="CDR0000062894__325"><h4>Sorafenib</h4><p id="CDR0000062894__326">Sorafenib is an orally available multikinase inhibitor (cRAF, bRAF, KIT, FLT-3, VEGFR-2, VEGFR-3, and PDGFR-β) and has also been approved for the treatment of patients with advanced renal cell carcinoma.[<a class="bk_pop" href="#CDR0000062894_rl_67_31">31</a>]</p><p id="CDR0000062894__327">In an international, multicenter, randomized trial with the primary endpoints of PFS and OS, 769 patients were stratified by the Memorial Sloan-Kettering Cancer Center prognostic risk category and by country and were randomly assigned to receive either sorafenib (400 mg bid) or a placebo. Approximately 82% of the patients had received IL-2 previously and/or interferon-alpha in both arms of the study. The median PFS for patients randomly assigned to sorafenib was 167 days compared with 84 days for patients randomly assigned to placebo (<i>P</i> < .001). The estimated HR for the risk of progression with sorafenib compared with a placebo was 0.44 (95% CI, 0.35–0.55). There was no significant difference in OS.[<a class="bk_pop" href="#CDR0000062894_rl_67_31">31</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335124/" class="def">Level of evidence: 1iDiii</a>] A subsequent phase II study of 189 patients randomly assigned to either sorafenib or interferon-alpha reported no difference (5.7 months vs. 5.6 months) in PFS, but sorafenib was associated with better quality of life than interferon-alpha.[<a class="bk_pop" href="#CDR0000062894_rl_67_35">35</a>]</p></div></div><div id="CDR0000062894__187"><h3>Chemotherapy</h3><p id="CDR0000062894__188">Responses to cytotoxic chemotherapy generally have not exceeded 10% for any regimen that has been studied in adequate numbers of patients.</p></div><div id="CDR0000062894__193"><h3>Treatment Options</h3><p id="CDR0000062894__190">Because of the lack of curative therapy for metastatic disease and the promise of targeted therapies, patients should be considered for the many ongoing clinical trials testing single or combination therapies, including the following:</p><ol id="CDR0000062894__218"><li class="half_rhythm"><div>Radical nephrectomy (for T4, M0 lesions).</div></li><li class="half_rhythm"><div>Cytoreductive nephrectomy (for any T, M1 lesions).[<a class="bk_pop" href="#CDR0000062894_rl_67_2">2</a>,<a class="bk_pop" href="#CDR0000062894_rl_67_3">3</a>]</div></li><li class="half_rhythm"><div>Temsirolimus.[<a class="bk_pop" href="#CDR0000062894_rl_67_22">22</a>]</div></li><li class="half_rhythm"><div>Sunitinib.[<a class="bk_pop" href="#CDR0000062894_rl_67_25">25</a>,<a class="bk_pop" href="#CDR0000062894_rl_67_26">26</a>]</div></li><li class="half_rhythm"><div>Pazopanib.[<a class="bk_pop" href="#CDR0000062894_rl_67_32">32</a>]</div></li><li class="half_rhythm"><div>Bevacizumab with or without interferon-alpha.[<a class="bk_pop" href="#CDR0000062894_rl_67_27">27</a>-<a class="bk_pop" href="#CDR0000062894_rl_67_29">29</a>,<a class="bk_pop" href="#CDR0000062894_rl_67_36">36</a>]</div></li><li class="half_rhythm"><div>Everolimus (for patients who have previously been treated with sunitinib and/or sorafenib).[<a class="bk_pop" href="#CDR0000062894_rl_67_23">23</a>] </div></li><li class="half_rhythm"><div>Sorafenib.[<a class="bk_pop" href="#CDR0000062894_rl_67_35">35</a>,<a class="bk_pop" href="#CDR0000062894_rl_67_37">37</a>]</div></li><li class="half_rhythm"><div>Axitinib.[<a class="bk_pop" href="#CDR0000062894_rl_67_30">30</a>]</div></li><li class="half_rhythm"><div>Interferon-alpha.[<a class="bk_pop" href="#CDR0000062894_rl_67_11">11</a>,<a class="bk_pop" href="#CDR0000062894_rl_67_21">21</a>,<a class="bk_pop" href="#CDR0000062894_rl_67_38">38</a>,<a class="bk_pop" href="#CDR0000062894_rl_67_39">39</a>]</div></li><li class="half_rhythm"><div>IL-2.[<a class="bk_pop" href="#CDR0000062894_rl_67_11">11</a>,<a class="bk_pop" href="#CDR0000062894_rl_67_17">17</a>,<a class="bk_pop" href="#CDR0000062894_rl_67_18">18</a>]</div></li><li class="half_rhythm"><div>Palliative EBRT.</div></li></ol></div><div id="CDR0000062894__TrialSearch_67_sid_8"><h3>Current Clinical Trials</h3><p id="CDR0000062894__TrialSearch_67_10">Check the list of NCI-supported cancer clinical trials that are now accepting patients with
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<a href="http://www.cancer.gov/search/ClinicalTrialsLink.aspx?Diagnosis=43693&tt=1&format=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">stage IV renal cell cancer</a> and <a href="http://www.cancer.gov/search/ClinicalTrialsLink.aspx?Diagnosis=43694&tt=1&format=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">recurrent renal cell cancer</a>. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.</p><p id="CDR0000062894__TrialSearch_67_18">General information about clinical trials is also available from the <a href="http://www.cancer.gov/about-cancer/treatment/clinical-trials" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCI website</a>.</p></div><div id="CDR0000062894_rl_67"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062894_rl_67_1">Kidney. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. 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[<a href="/pmc/articles/PMC2275324/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2275324</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/12890841" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12890841</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062894_rl_67_28">Rini BI, Halabi S, Rosenberg JE, et al.: Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol 26 (33): 5422-8, 2008. [<a href="/pmc/articles/PMC2651074/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2651074</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/18936475" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18936475</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062894_rl_67_29">Escudier B, Pluzanska A, Koralewski P, et al.: Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet 370 (9605): 2103-11, 2007. [<a href="https://pubmed.ncbi.nlm.nih.gov/18156031" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18156031</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062894_rl_67_30">Motzer RJ, Escudier B, Tomczak P, et al.: Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: overall survival analysis and updated results from a randomised phase 3 trial. Lancet Oncol 14 (6): 552-62, 2013. [<a href="https://pubmed.ncbi.nlm.nih.gov/23598172" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23598172</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062894_rl_67_31">Nexavar® [label information]. Rockville, Md: Center for Drug Evaluation and Research, FDA, 2007. <a href="http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021923s004s005s006s007lbl.pdf" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">Available online</a>. Last accessed February 9, 2012.</div></li><li><div class="bk_ref" id="CDR0000062894_rl_67_32">Sternberg CN, Davis ID, Mardiak J, et al.: Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 28 (6): 1061-8, 2010. [<a href="https://pubmed.ncbi.nlm.nih.gov/20100962" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20100962</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062894_rl_67_33">Motzer RJ, Hutson TE, Cella D, et al.: Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med 369 (8): 722-31, 2013. [<a href="https://pubmed.ncbi.nlm.nih.gov/23964934" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23964934</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062894_rl_67_34">Escudier B, Porta C, Bono P, et al.: Randomized, controlled, double-blind, cross-over trial assessing treatment preference for pazopanib versus sunitinib in patients with metastatic renal cell carcinoma: PISCES Study. J Clin Oncol 32 (14): 1412-8, 2014. [<a href="https://pubmed.ncbi.nlm.nih.gov/24687826" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24687826</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062894_rl_67_35">Escudier B, Szczylik C, Hutson TE, et al.: Randomized phase II trial of first-line treatment with sorafenib versus interferon Alfa-2a in patients with metastatic renal cell carcinoma. J Clin Oncol 27 (8): 1280-9, 2009. [<a href="https://pubmed.ncbi.nlm.nih.gov/19171708" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19171708</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062894_rl_67_36">Escudier B, Bellmunt J, Négrier S, et al.: Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (AVOREN): final analysis of overall survival. J Clin Oncol 28 (13): 2144-50, 2010. [<a href="https://pubmed.ncbi.nlm.nih.gov/20368553" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20368553</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062894_rl_67_37">Escudier B, Eisen T, Stadler WM, et al.: Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356 (2): 125-34, 2007. [<a href="https://pubmed.ncbi.nlm.nih.gov/17215530" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17215530</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062894_rl_67_38">Pyrhönen S, Salminen E, Ruutu M, et al.: Prospective randomized trial of interferon alfa-2a plus vinblastine versus vinblastine alone in patients with advanced renal cell cancer. J Clin Oncol 17 (9): 2859-67, 1999. [<a href="https://pubmed.ncbi.nlm.nih.gov/10561363" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10561363</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062894_rl_67_39">Interferon-alpha and survival in metastatic renal carcinoma: early results of a randomised controlled trial. Medical Research Council Renal Cancer Collaborators. Lancet 353 (9146): 14-7, 1999. [<a href="https://pubmed.ncbi.nlm.nih.gov/10023944" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10023944</span></a>]</div></li></ol></div></div><div id="CDR0000062894__93"><h2 id="_CDR0000062894__93_">Changes to This Summary (04/28/2015)</h2><p id="CDR0000062894__94">The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.</p><p id="CDR0000062894__329"><b><a href="#CDR0000062894__1">General Information About Renal Cell Cancer</a></b></p><p id="CDR0000062894__338">Editorial changes were made to this section.</p><p id="CDR0000062894__disclaimerHP_3">This summary is written and maintained by the <a href="http://www.cancer.gov/publications/pdq/editorial-boards/adult-treatment" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ Adult Treatment Editorial Board</a>, which is
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</p></div><div id="CDR0000062894__AboutThis_1"><h2 id="_CDR0000062894__AboutThis_1_">About This PDQ Summary</h2><div id="CDR0000062894__AboutThis_2"><h3>Purpose of This Summary</h3><p id="CDR0000062894__AboutThis_3">This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of renal cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.</p></div><div id="CDR0000062894__AboutThis_4"><h3>Reviewers and Updates</h3><p id="CDR0000062894__AboutThis_5">This summary is reviewed regularly and updated as necessary by the <a href="http://www.cancer.gov/publications/pdq/editorial-boards/adult-treatment" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ Adult Treatment Editorial Board</a>, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).</p><p id="CDR0000062894__AboutThis_22"> Board members review recently published articles each month to determine whether an article should:</p><ul id="CDR0000062894__AboutThis_6"><li class="half_rhythm"><div>be discussed at a meeting,</div></li><li class="half_rhythm"><div>be cited with text, or</div></li><li class="half_rhythm"><div>replace or update an existing article that is already cited.</div></li></ul><p id="CDR0000062894__AboutThis_7">Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.</p><p>The lead reviewer for Renal Cell Cancer Treatment is:</p><ul><li class="half_rhythm"><div>Timothy Gilligan, MD (Cleveland Clinic Taussig Cancer Institute)</div></li></ul><p id="CDR0000062894__AboutThis_9">Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's <a href="http://www.cancer.gov/contact/email-us" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Email Us</a>. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.</p></div><div id="CDR0000062894__AboutThis_10"><h3>Levels of Evidence</h3><p id="CDR0000062894__AboutThis_11">Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a <a href="/books/n/pdqcis/CDR0000062796/">formal evidence ranking system</a> in developing its level-of-evidence designations.</p></div><div id="CDR0000062894__AboutThis_12"><h3>Permission to Use This Summary</h3><p id="CDR0000062894__AboutThis_13">PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”</p><p id="CDR0000062894__AboutThis_14">The preferred citation for this PDQ summary is:</p><p id="CDR0000062894__AboutThis_15">National Cancer Institute: PDQ® Renal Cell Cancer Treatment. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: <a href="http://www.cancer.gov/types/kidney/hp/kidney-treatment-pdq" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">http://www.cancer.gov/types/kidney/hp/kidney-treatment-pdq</a>. Accessed <MM/DD/YYYY>.</p><p id="CDR0000062894__AboutThis_16">Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in <a href="http://visualsonline.cancer.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Visuals Online</a>, a collection of over 2,000 scientific images.
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</p></div><div id="CDR0000062894__AboutThis_17"><h3>Disclaimer</h3><p id="CDR0000062894__AboutThis_18">Based on the strength of the available evidence, treatment options may be described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the <a href="http://www.cancer.gov/about-cancer/managing-care" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Managing Cancer Care</a> page.</p></div><div id="CDR0000062894__AboutThis_20"><h3>Contact Us</h3><p id="CDR0000062894__AboutThis_21">More information about contacting us or receiving help with the Cancer.gov website can be found on our <a href="http://www.cancer.gov/contact" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Contact Us for Help</a> page. Questions can also be submitted to Cancer.gov through the website’s <a href="http://www.cancer.gov/contact/email-us" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Email Us</a>.</p></div></div><div id="CDR0000062894__GetMore_3"><h2 id="_CDR0000062894__GetMore_3_">Get More Information From NCI</h2><p id="CDR0000062894__GetMore_15"><i><b>Call 1-800-4-CANCER</b></i></p><p id="CDR0000062894__GetMore_16">For more information, U.S. residents may call the National Cancer Institute's (NCI's) Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 8:00 a.m. to 8:00 p.m., Eastern Time. A trained Cancer Information Specialist is available to answer your questions.</p><p id="CDR0000062894__GetMore_25"><i><b>Chat online
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href="#CDR0000062894__7" ref="log$=inpage&link_id=inpage">Stage Information for Renal Cell Cancer</a></li><li><a href="#CDR0000062894__31" ref="log$=inpage&link_id=inpage">Treatment Option Overview</a></li><li><a href="#CDR0000062894__33" ref="log$=inpage&link_id=inpage">Stage I Renal Cell Cancer</a></li><li><a href="#CDR0000062894__43" ref="log$=inpage&link_id=inpage">Stage II Renal Cell Cancer</a></li><li><a href="#CDR0000062894__53" ref="log$=inpage&link_id=inpage">Stage III Renal Cell Cancer</a></li><li><a href="#CDR0000062894__67" ref="log$=inpage&link_id=inpage">Stage IV and Recurrent Renal Cell Cancer</a></li><li><a href="#CDR0000062894__93" ref="log$=inpage&link_id=inpage">Changes to This Summary (04/28/2015)</a></li><li><a href="#CDR0000062894__AboutThis_1" ref="log$=inpage&link_id=inpage">About This PDQ Summary</a></li><li><a href="#CDR0000062894__GetMore_3" ref="log$=inpage&link_id=inpage">Get More Information From NCI</a></li></ul></div></div><div class="portlet"><div 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Carcinoma (PDQ®): Health Professional Version.</a><span class="source">[PDQ Cancer Information Summari...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Genetics of Renal Cell Carcinoma (PDQ®): Health Professional Version.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">PDQ Cancer Genetics Editorial Board. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">PDQ Cancer Information Summaries. 2002</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/26389393" ref="ordinalpos=1&linkpos=2&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Adrenocortical Carcinoma Treatment (PDQ®): Health Professional Version.</a><span class="source">[PDQ Cancer Information Summari...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Adrenocortical Carcinoma Treatment (PDQ®): Health Professional Version.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">PDQ Adult Treatment Editorial Board. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">PDQ Cancer Information Summaries. 2002</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/26389244" ref="ordinalpos=1&linkpos=3&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Lymphedema (PDQ®): Health Professional Version.</a><span class="source">[PDQ Cancer Information Summari...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Lymphedema (PDQ®): Health Professional Version.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">PDQ Supportive and Palliative Care Editorial Board. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">PDQ Cancer Information Summaries. 2002</em></div></div></li><li class="brieflinkpopper two_line"><a 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2002</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/26389190" ref="ordinalpos=1&linkpos=5&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Neuroblastoma Treatment (PDQ®): Health Professional Version.</a><span class="source">[PDQ Cancer Information Summari...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Neuroblastoma Treatment (PDQ®): Health Professional Version.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">PDQ Pediatric Treatment Editorial Board. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">PDQ Cancer Information Summaries. 2002</em></div></div></li></ul><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed_reviews&uid=26389256" ref="ordinalpos=1&log$=relatedreviews_seeall&logdbfrom=pubmed">See reviews...</a><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed&uid=26389256" ref="ordinalpos=1&log$=relatedarticles_seeall&logdbfrom=pubmed">See all...</a></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Recent Activity</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="recent_activity" id="Shutter"></a></div><div class="portlet_content"><div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" id="HTDisplay" class=""><div class="action"><a href="javascript:historyDisplayState('ClearHT')">Clear</a><a 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<path class="st10" d="M159,99.1h-24V88.4c0-5,3.3-6.2,5.7-6.2h16.8V60l-24.4-0.1c-22.1,0-26.2,16.5-26.2,27.1v12.1H90v22.5h16.9 v67.5H135v-67.5h21.7L159,99.1z"></path>
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<title>Youtube</title>
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<path class="st5" d="M88.4,1037.4c-10.4,0-18.7,8.3-18.7,18.7v40.1c0,10.4,8.3,18.7,18.7,18.7h72.1c10.4,0,18.7-8.3,18.7-18.7 v-40.1c0-10.4-8.3-18.7-18.7-18.7H88.4z M115.2,1058.8l29.4,17.4l-29.4,17.4V1058.8z"></path>
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<p><a href="https://www.nlm.nih.gov/web_policies.html" class="text-white">Web Policies</a><br />
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<a href="https://www.nih.gov/institutes-nih/nih-office-director/office-communications-public-liaison/freedom-information-act-office" class="text-white">FOIA</a><br />
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<p><a class="supportLink text-white" href="https://support.nlm.nih.gov/">Help</a><br />
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<a href="https://www.nlm.nih.gov/accessibility.html" class="text-white">Accessibility</a><br />
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<a href="https://www.nlm.nih.gov/careers/careers.html" class="text-white">Careers</a></p>
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