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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="#__NBK65719_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK65719_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="_NBK65719_"><span class="title" itemprop="name">Thyroid 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: February 4, 2016.</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="CDR0000062913__418">This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of thyroid 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="CDR0000062913__419">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="CDR0000062913__1"><h2 id="_CDR0000062913__1_">General Information About Thyroid Cancer</h2><div id="CDR0000062913__304"><h3>Incidence and Mortality</h3><p id="CDR0000062913__243">Estimated new cases and deaths from thyroid cancer in the United States in 2016:[<a class="bk_pop" href="#CDR0000062913_rl_1_1">1</a>]</p><ul id="CDR0000062913__244"><li class="half_rhythm"><div>New cases: 64,300.</div></li><li class="half_rhythm"><div>Deaths: 1,980.</div></li></ul><p id="CDR0000062913__312">Differentiated tumors
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(papillary or follicular) are highly treatable and usually curable. Poorly differentiated tumors (medullary or anaplastic) are much less common, are
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aggressive, metastasize early, and have a much poorer prognosis. Thyroid
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cancer affects women more often than men and usually occurs in
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people between the ages of 25 and 65 years. The incidence of this malignancy has
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|
been increasing over the last decade. Thyroid cancer commonly presents
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as a cold nodule. The overall incidence of cancer in a cold nodule is 12% to
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15%, but it is higher in people younger than 40 years and in people with calcifications present on preoperative ultrasonography.[<a class="bk_pop" href="#CDR0000062913_rl_1_2">2</a>,<a class="bk_pop" href="#CDR0000062913_rl_1_3">3</a>]</p></div><div id="CDR0000062913__313"><h3>Risk Factors</h3><p id="CDR0000062913__314">Patients with a history of radiation administered in infancy and childhood for
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benign conditions of the head and neck, such as enlarged thymus, acne, or
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tonsillar or adenoidal enlargement, have an increased risk of cancer as well as
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other abnormalities of the thyroid gland. In this group of patients,
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malignancies of the thyroid gland first appear beginning as early as 5 years
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following radiation and may appear 20 or more years later.[<a class="bk_pop" href="#CDR0000062913_rl_1_4">4</a>] Radiation exposure as a consequence of nuclear fallout has also been associated with a high risk of thyroid cancer, especially in children.[<a class="bk_pop" href="#CDR0000062913_rl_1_5">5</a>-<a class="bk_pop" href="#CDR0000062913_rl_1_7">7</a>] Other risk
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factors for the development of thyroid cancer include the following:[<a class="bk_pop" href="#CDR0000062913_rl_1_8">8</a>]</p><ul id="CDR0000062913__315"><li class="half_rhythm"><div>A history of goiter.</div></li><li class="half_rhythm"><div>Family history of thyroid disease.</div></li><li class="half_rhythm"><div>Female gender.</div></li><li class="half_rhythm"><div>Asian race.</div></li></ul></div><div id="CDR0000062913__316"><h3>Prognostic Factors</h3><p id="CDR0000062913__317">The prognosis for differentiated
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carcinoma is better for patients younger than 40 years without
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extracapsular extension or vascular invasion.[<a class="bk_pop" href="#CDR0000062913_rl_1_9">9</a>-<a class="bk_pop" href="#CDR0000062913_rl_1_13">13</a>] Age appears to be the
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single most important prognostic factor.[<a class="bk_pop" href="#CDR0000062913_rl_1_11">11</a>] The prognostic significance of lymph node status is controversial. One
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retrospective surgical series of 931 previously untreated patients with
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differentiated thyroid cancer found that female gender, multifocality, and
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regional node involvement are favorable prognostic factors.[<a class="bk_pop" href="#CDR0000062913_rl_1_14">14</a>] Adverse factors
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included age older than 45 years, follicular histology, primary tumor larger than 4
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cm (T2–T3), extrathyroid extension (T4), and distant metastases.[<a class="bk_pop" href="#CDR0000062913_rl_1_14">14</a>,<a class="bk_pop" href="#CDR0000062913_rl_1_15">15</a>]
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Other studies, however, have shown that regional lymph node involvement had no
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effect [<a class="bk_pop" href="#CDR0000062913_rl_1_16">16</a>,<a class="bk_pop" href="#CDR0000062913_rl_1_17">17</a>] or even an adverse effect on survival.[<a class="bk_pop" href="#CDR0000062913_rl_1_12">12</a>,<a class="bk_pop" href="#CDR0000062913_rl_1_13">13</a>,<a class="bk_pop" href="#CDR0000062913_rl_1_18">18</a>] Use of sentinel lymph node biopsy may aid in identifying patients with occult metastases who might benefit from central neck dissection.[<a class="bk_pop" href="#CDR0000062913_rl_1_19">19</a>]</p><div id="CDR0000062913__387"><h4>Risk factors and survivorship</h4><p id="CDR0000062913__318">Diffuse, intense
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immunostaining for vascular endothelial growth factor in patients with
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papillary cancer has been associated with a high rate of local recurrence and
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distant metastases.[<a class="bk_pop" href="#CDR0000062913_rl_1_20">20</a>] An elevated serum thyroglobulin level correlates
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strongly with recurrent tumor when found in patients with differentiated
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thyroid cancer during postoperative evaluations.[<a class="bk_pop" href="#CDR0000062913_rl_1_21">21</a>,<a class="bk_pop" href="#CDR0000062913_rl_1_22">22</a>] Serum thyroglobulin
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levels are most sensitive when patients are hypothyroid and have elevated serum
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thyroid-stimulating hormone levels.[<a class="bk_pop" href="#CDR0000062913_rl_1_23">23</a>] Expression of the tumor suppressor
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gene <i>p53</i> has also been associated with an adverse prognosis for patients with
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thyroid cancer.[<a class="bk_pop" href="#CDR0000062913_rl_1_24">24</a>]</p></div><div id="CDR0000062913__388"><h4>Low-risk factors</h4><p id="CDR0000062913__319">Patients considered at low risk by the age, metastases, extent, and size
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(AMES) risk criteria include women younger than 50 years and men younger
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than 40 years without evidence of distant metastases. Also included in
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the low-risk group are older patients with primary tumors smaller than 5
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cm and papillary cancer without evidence of gross extrathyroidal
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invasion or follicular cancer without either major capsular invasion or blood
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vessel invasion.[<a class="bk_pop" href="#CDR0000062913_rl_1_10">10</a>] Using these criteria, a retrospective study of 1,019
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patients showed that the 20-year survival rate is 98% for low-risk patients and
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50% for high-risk patients.[<a class="bk_pop" href="#CDR0000062913_rl_1_10">10</a>] The 10-year overall relative survival rates for patients in the United States are 93% for papillary cancer, 85% for follicular cancer, 75% for medullary cancer, and 14% for undifferentiated/anaplastic cancer.[<a class="bk_pop" href="#CDR0000062913_rl_1_25">25</a>]</p><p id="CDR0000062913__4">
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The
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thyroid gland may occasionally be the site of other primary tumors, including
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sarcomas, lymphomas, epidermoid carcinomas, and teratomas and may be the site
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of metastasis from other cancers, particularly of the lung, breast, and kidney.
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</p></div></div><div id="CDR0000062913__320"><h3>Related Summaries</h3><p id="CDR0000062913__321">Other PDQ summaries containing information related to thyroid cancer include the following: </p><ul id="CDR0000062913__322"><li class="half_rhythm"><div><a href="/books/n/pdqcis/CDR0000062890/">Genetics of Endocrine and Neuroendocrine Neoplasias</a></div></li><li class="half_rhythm"><div><a href="/books/n/pdqcis/CDR0000062872/#CDR0000062872__108">Unusual Cancers of Childhood</a> (childhood cancer of the thyroid)</div></li></ul></div><div id="CDR0000062913_rl_1"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062913_rl_1_1">American Cancer Society: Cancer Facts and Figures 2016. Atlanta, Ga: American Cancer Society, 2016. <a href="http://www.cancer.org/acs/groups/content/@research/documents/document/acspc-047079.pdf" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">Available online.</a> Last accessed July 11, 2016.</div></li><li><div class="bk_ref" id="CDR0000062913_rl_1_2">Tennvall J, Biörklund A, Möller T, et al.: Is the EORTC prognostic index of thyroid cancer valid in differentiated thyroid carcinoma? Retrospective multivariate analysis of differentiated thyroid carcinoma with long follow-up. Cancer 57 (7): 1405-14, 1986. [<a href="https://pubmed.ncbi.nlm.nih.gov/3948123" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3948123</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_1_3">Khoo ML, Asa SL, Witterick IJ, et al.: Thyroid calcification and its association with thyroid carcinoma. Head Neck 24 (7): 651-5, 2002. [<a href="https://pubmed.ncbi.nlm.nih.gov/12112538" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12112538</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_1_4">Carling T, Udelsman R: Thyroid tumors. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1457-72.</div></li><li><div class="bk_ref" id="CDR0000062913_rl_1_5">Pacini F, Vorontsova T, Molinaro E, et al.: Prevalence of thyroid autoantibodies in children and adolescents from Belarus exposed to the Chernobyl radioactive fallout. Lancet 352 (9130): 763-6, 1998. [<a href="https://pubmed.ncbi.nlm.nih.gov/9737280" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9737280</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_1_6">Cardis E, Kesminiene A, Ivanov V, et al.: Risk of thyroid cancer after exposure to 131I in childhood. J Natl Cancer Inst 97 (10): 724-32, 2005. [<a href="https://pubmed.ncbi.nlm.nih.gov/15900042" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15900042</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_1_7">Tronko MD, Howe GR, Bogdanova TI, et al.: A cohort study of thyroid cancer and other thyroid diseases after the chornobyl accident: thyroid cancer in Ukraine detected during first screening. J Natl Cancer Inst 98 (13): 897-903, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/16818853" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16818853</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_1_8">Iribarren C, Haselkorn T, Tekawa IS, et al.: Cohort study of thyroid cancer in a San Francisco Bay area population. Int J Cancer 93 (5): 745-50, 2001. [<a href="https://pubmed.ncbi.nlm.nih.gov/11477590" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11477590</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_1_9">Grant CS, Hay ID, Gough IR, et al.: Local recurrence in papillary thyroid carcinoma: is extent of surgical resection important? Surgery 104 (6): 954-62, 1988. [<a href="https://pubmed.ncbi.nlm.nih.gov/3194847" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3194847</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_1_10">Sanders LE, Cady B: Differentiated thyroid cancer: reexamination of risk groups and outcome of treatment. Arch Surg 133 (4): 419-25, 1998. [<a href="https://pubmed.ncbi.nlm.nih.gov/9565123" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9565123</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_1_11">Mazzaferri EL: Treating differentiated thyroid carcinoma: where do we draw the line? Mayo Clin Proc 66 (1): 105-11, 1991. [<a href="https://pubmed.ncbi.nlm.nih.gov/1988750" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1988750</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_1_12">Staunton MD: Thyroid cancer: a multivariate analysis on influence of treatment on long-term survival. Eur J Surg Oncol 20 (6): 613-21, 1994. [<a href="https://pubmed.ncbi.nlm.nih.gov/7995409" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7995409</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_1_13">Mazzaferri EL, Jhiang SM: Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med 97 (5): 418-28, 1994. [<a href="https://pubmed.ncbi.nlm.nih.gov/7977430" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7977430</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_1_14">Shah JP, Loree TR, Dharker D, et al.: Prognostic factors in differentiated carcinoma of the thyroid gland. Am J Surg 164 (6): 658-61, 1992. [<a href="https://pubmed.ncbi.nlm.nih.gov/1463119" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1463119</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_1_15">Andersen PE, Kinsella J, Loree TR, et al.: Differentiated carcinoma of the thyroid with extrathyroidal extension. Am J Surg 170 (5): 467-70, 1995. [<a href="https://pubmed.ncbi.nlm.nih.gov/7485734" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7485734</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_1_16">Coburn MC, Wanebo HJ: Prognostic factors and management considerations in patients with cervical metastases of thyroid cancer. Am J Surg 164 (6): 671-6, 1992. [<a href="https://pubmed.ncbi.nlm.nih.gov/1463122" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1463122</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_1_17">Voutilainen PE, Multanen MM, Leppäniemi AK, et al.: Prognosis after lymph node recurrence in papillary thyroid carcinoma depends on age. Thyroid 11 (10): 953-7, 2001. [<a href="https://pubmed.ncbi.nlm.nih.gov/11716043" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11716043</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_1_18">Sellers M, Beenken S, Blankenship A, et al.: Prognostic significance of cervical lymph node metastases in differentiated thyroid cancer. Am J Surg 164 (6): 578-81, 1992. [<a href="https://pubmed.ncbi.nlm.nih.gov/1463103" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1463103</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_1_19">Cunningham DK, Yao KA, Turner RR, et al.: Sentinel lymph node biopsy for papillary thyroid cancer: 12 years of experience at a single institution. Ann Surg Oncol 17 (11): 2970-5, 2010. [<a href="https://pubmed.ncbi.nlm.nih.gov/20552407" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20552407</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_1_20">Lennard CM, Patel A, Wilson J, et al.: Intensity of vascular endothelial growth factor expression is associated with increased risk of recurrence and decreased disease-free survival in papillary thyroid cancer. Surgery 129 (5): 552-8, 2001. [<a href="https://pubmed.ncbi.nlm.nih.gov/11331447" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11331447</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_1_21">van Herle AJ, van Herle KA: Thyroglobulin in benign and malignant thyroid disease. In: Falk SA: Thyroid Disease: Endocrinology, Surgery, Nuclear Medicine, and Radiotherapy. Philadelphia, Pa: Lippincott-Raven, 1997, pp 601-618.</div></li><li><div class="bk_ref" id="CDR0000062913_rl_1_22">Ruiz-Garcia J, Ruiz de Almodóvar JM, Olea N, et al.: Thyroglobulin level as a predictive factor of tumoral recurrence in differentiated thyroid cancer. J Nucl Med 32 (3): 395-8, 1991. [<a href="https://pubmed.ncbi.nlm.nih.gov/2005446" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2005446</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_1_23">Duren M, Siperstein AE, Shen W, et al.: Value of stimulated serum thyroglobulin levels for detecting persistent or recurrent differentiated thyroid cancer in high- and low-risk patients. Surgery 126 (1): 13-9, 1999. [<a href="https://pubmed.ncbi.nlm.nih.gov/10418587" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10418587</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_1_24">Godballe C, Asschenfeldt P, Jørgensen KE, et al.: Prognostic factors in papillary and follicular thyroid carcinomas: p53 expression is a significant indicator of prognosis. Laryngoscope 108 (2): 243-9, 1998. [<a href="https://pubmed.ncbi.nlm.nih.gov/9473076" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9473076</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_1_25">Hundahl SA, Fleming ID, Fremgen AM, et al.: A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985-1995 [see comments] Cancer 83 (12): 2638-48, 1998. [<a href="https://pubmed.ncbi.nlm.nih.gov/9874472" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9874472</span></a>]</div></li></ol></div></div><div id="CDR0000062913__6"><h2 id="_CDR0000062913__6_">Cellular Classification of Thyroid Cancer</h2><p id="CDR0000062913__7">Cell type is an important determinant of prognosis in thyroid cancer. There
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are four main varieties of thyroid cancer (although, for clinical management of
|
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the patient, thyroid cancer is generally divided into two categories: well differentiated or
|
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poorly differentiated):[<a class="bk_pop" href="#CDR0000062913_rl_6_1">1</a>]
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</p><ul id="CDR0000062913__186"><li class="half_rhythm"><div>Papillary carcinoma.
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<dl id="CDR0000062913__9" class="temp-labeled-list"><dt>-</dt><dd><p class="no_top_margin">Papillary/follicular carcinoma.
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</p></dd></dl></div></li><li class="half_rhythm"><div>Follicular carcinoma.<dl id="CDR0000062913__10" class="temp-labeled-list"><dt>-</dt><dd><p class="no_top_margin">Hürthle cell carcinoma, a variant of follicular carcinoma with a poorer prognosis.[<a class="bk_pop" href="#CDR0000062913_rl_6_2">2</a>,<a class="bk_pop" href="#CDR0000062913_rl_6_3">3</a>]
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</p></dd></dl></div></li><li class="half_rhythm"><div>Medullary carcinoma.</div></li><li class="half_rhythm"><div>Anaplastic carcinoma.<dl id="CDR0000062913__11" class="temp-labeled-list"><dt>-</dt><dd><p class="no_top_margin">Small cell carcinoma.
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</p></dd><dt>-</dt><dd><p class="no_top_margin">Giant cell carcinoma.
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</p></dd></dl></div></li><li class="half_rhythm"><div>Others.<dl id="CDR0000062913__12" class="temp-labeled-list"><dt>-</dt><dd><p class="no_top_margin">Lymphoma.
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</p></dd><dt>-</dt><dd><p class="no_top_margin">Sarcoma.
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</p></dd><dt>-</dt><dd><p class="no_top_margin">Carcinosarcoma.
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</p></dd></dl></div></li></ul><p id="CDR0000062913__13">A definition for each major type can be found under stage information.
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</p><div id="CDR0000062913_rl_6"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062913_rl_6_1">LiVolsi VA: Pathology of thyroid disease. In: Falk SA: Thyroid Disease: Endocrinology, Surgery, Nuclear Medicine, and Radiotherapy. Philadelphia, Pa: Lippincott-Raven, 1997, pp 127-175.</div></li><li><div class="bk_ref" id="CDR0000062913_rl_6_2">Kushchayeva Y, Duh QY, Kebebew E, et al.: Comparison of clinical characteristics at diagnosis and during follow-up in 118 patients with Hurthle cell or follicular thyroid cancer. Am J Surg 195 (4): 457-62, 2008. [<a href="https://pubmed.ncbi.nlm.nih.gov/18070728" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18070728</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_6_3">Mills SC, Haq M, Smellie WJ, et al.: Hürthle cell carcinoma of the thyroid: Retrospective review of 62 patients treated at the Royal Marsden Hospital between 1946 and 2003. Eur J Surg Oncol 35 (3): 230-4, 2009. [<a href="https://pubmed.ncbi.nlm.nih.gov/18722077" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18722077</span></a>]</div></li></ol></div></div><div id="CDR0000062913__14"><h2 id="_CDR0000062913__14_">Stage Information for Thyroid Cancer</h2><div id="CDR0000062913__298"><h3>Definitions of TNM</h3><p id="CDR0000062913__301">The American Joint Committee on Cancer (AJCC) has designated staging by TNM
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classification to define thyroid cancer.[<a class="bk_pop" href="#CDR0000062913_rl_14_1">1</a>]</p><div id="CDR0000062913__299" class="table"><h3><span class="title">Table 1. Primary Tumor (T)<sup>a,</sup><sup>b</sup></span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK65719.3/table/CDR0000062913__299/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000062913__299_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 ≤2 cm in greatest dimension limited to the thyroid.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T1a</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor ≤1 cm, limited to the thyroid.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T1b</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor >1 cm but ≤2 cm in greatest dimension, limited to the thyroid.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T2</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor >2 cm but ≤4 cm in greatest dimension, limited to the thyroid.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T3</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor >4 cm in greatest dimension limited to the thyroid or any tumor with minimal extrathyroid extension (e.g., extension to sternothyroid muscle or perithyroid soft tissues).</td></tr><tr><td colspan="1" rowspan="2" style="vertical-align:top;">T4a</td><td colspan="1" rowspan="1" style="vertical-align:top;">Moderately advanced disease.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues, larynx, trachea, esophagus, or recurrent laryngeal nerve.</td></tr><tr><td colspan="1" rowspan="2" style="vertical-align:top;">T4b</td><td colspan="1" rowspan="1" style="vertical-align:top;">Very advanced disease.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"><sup>c</sup>T4a</td><td colspan="1" rowspan="1" style="vertical-align:top;">Intrathyroidal anaplastic carcinoma.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"><sup>c</sup>T4b</td><td colspan="1" rowspan="1" style="vertical-align:top;">Anaplastic carcinoma with gross extrathyroid extension.</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: Thyroid. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 87-96.</p></div></dd><dt></dt><dd><div><p class="no_margin"><sup>b</sup>All categories may be subdivided: (s) solitary tumor and (m) multifocal tumor (the largest determines the classification).</p></div></dd><dt></dt><dd><div><p class="no_margin"><sup>c</sup>All anaplastic carcinomas are considered T4 tumors.</p></div></dd></dl></div></div></div><div id="CDR0000062913__290" class="table"><h3><span class="title">Table 2. Regional Lymph Nodes (N)<sup>a,</sup><sup>b</sup></span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK65719.3/table/CDR0000062913__290/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000062913__290_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;">Regional lymph node metastasis.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">N1a</td><td colspan="1" rowspan="1" style="vertical-align:top;">Metastases to Level VI (pretracheal, paratracheal, and prelaryngeal/Delphian lymph nodes).</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">N1b</td><td colspan="1" rowspan="1" style="vertical-align:top;">Metastases to unilateral, bilateral, or contralateral cervical (Levels I, II, III, IV, or V) or retropharyngeal or superior mediastinal lymph nodes (Level VII).</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: Thyroid. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 87-96.</p></div></dd><dt></dt><dd><div><p class="no_margin"><sup>b</sup>Regional lymph nodes are the central compartment, lateral cervical, and upper mediastinal lymph nodes.</p></div></dd></dl></div></div></div><div id="CDR0000062913__308" 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/NBK65719.3/table/CDR0000062913__308/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000062913__308_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: Thyroid. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 87-96.</p></div></dd></dl></div></div></div><div id="CDR0000062913__302" class="table"><h3><span class="title">Table 4. Anatomic Stage/Prognostic Groups<sup>a,</sup><sup>b</sup></span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK65719.3/table/CDR0000062913__302/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000062913__302_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="4" rowspan="1" style="text-align:center;vertical-align:top;"><i>Papillary or follicular (differentiated)</i></td></tr><tr><td colspan="4" rowspan="1" style="text-align:center;vertical-align:top;">YOUNGER THAN 45 YEARS</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"> I</td><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;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"> II</td><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><tr><td colspan="4" rowspan="1" style="text-align:center;vertical-align:top;">45 YEARS AND OLDER</td></tr><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="1" style="vertical-align:top;"> III</td><td colspan="1" rowspan="1" style="vertical-align:top;">T3</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;"></td><td colspan="1" rowspan="1" style="vertical-align:top;">T1</td><td colspan="1" rowspan="1" style="vertical-align:top;">N1a</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"></td><td colspan="1" rowspan="1" style="vertical-align:top;">T2</td><td colspan="1" rowspan="1" style="vertical-align:top;">N1a</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"></td><td colspan="1" rowspan="1" style="vertical-align:top;">T3</td><td colspan="1" rowspan="1" style="vertical-align:top;">N1a</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"> IVA</td><td colspan="1" rowspan="1" style="vertical-align:top;">T4a</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;"></td><td colspan="1" rowspan="1" style="vertical-align:top;">T4a</td><td colspan="1" rowspan="1" style="vertical-align:top;">N1a</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"></td><td colspan="1" rowspan="1" style="vertical-align:top;">T1</td><td colspan="1" rowspan="1" style="vertical-align:top;">N1b</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"></td><td colspan="1" rowspan="1" style="vertical-align:top;">T2</td><td colspan="1" rowspan="1" style="vertical-align:top;">N1b</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"></td><td colspan="1" rowspan="1" style="vertical-align:top;">T3</td><td colspan="1" rowspan="1" style="vertical-align:top;">N1b</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"></td><td colspan="1" rowspan="1" style="vertical-align:top;">T4a</td><td colspan="1" rowspan="1" style="vertical-align:top;">N1b</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"> IVB</td><td colspan="1" rowspan="1" style="vertical-align:top;">T4b</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;">Stage IVC</td><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><tr><td colspan="4" rowspan="1" style="text-align:center;vertical-align:top;"><i>Medullary carcinoma (all age groups)</i></td></tr><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="1" style="vertical-align:top;"></td><td colspan="1" rowspan="1" style="vertical-align:top;">T3</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;">III</td><td colspan="1" rowspan="1" style="vertical-align:top;">T1</td><td colspan="1" rowspan="1" style="vertical-align:top;">N1a</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"></td><td colspan="1" rowspan="1" style="vertical-align:top;">T1</td><td colspan="1" rowspan="1" style="vertical-align:top;">N1a</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"></td><td colspan="1" rowspan="1" style="vertical-align:top;">T2</td><td colspan="1" rowspan="1" style="vertical-align:top;">N1a</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"></td><td colspan="1" rowspan="1" style="vertical-align:top;">T3</td><td colspan="1" rowspan="1" style="vertical-align:top;">N1a</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">IVA</td><td colspan="1" rowspan="1" style="vertical-align:top;">T4a</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;"></td><td colspan="1" rowspan="1" style="vertical-align:top;">T4a</td><td colspan="1" rowspan="1" style="vertical-align:top;">N1a</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"></td><td colspan="1" rowspan="1" style="vertical-align:top;">T1</td><td colspan="1" rowspan="1" style="vertical-align:top;">N1b</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"></td><td colspan="1" rowspan="1" style="vertical-align:top;">T2</td><td colspan="1" rowspan="1" style="vertical-align:top;">N1b</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"></td><td colspan="1" rowspan="1" style="vertical-align:top;">T3</td><td colspan="1" rowspan="1" style="vertical-align:top;">N1b</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"></td><td colspan="1" rowspan="1" style="vertical-align:top;">T4a</td><td colspan="1" rowspan="1" style="vertical-align:top;">N1b</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"></td><td colspan="1" rowspan="1" style="vertical-align:top;">Stage IVB</td><td colspan="1" rowspan="1" style="vertical-align:top;">T4b</td><td colspan="1" rowspan="1" style="vertical-align:top;">Any N</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">IVB</td><td colspan="1" rowspan="1" style="vertical-align:top;">T4b</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;"> IVC</td><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><tr><td colspan="4" rowspan="1" style="text-align:center;vertical-align:top;"><i>Anaplastic carcinoma</i><sup>c</sup></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">IVA</td><td colspan="1" rowspan="1" style="vertical-align:top;">T4a</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;">IVB</td><td colspan="1" rowspan="1" style="vertical-align:top;">T4b</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;">IVC</td><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: Thyroid. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 87-96.</p></div></dd><dt></dt><dd><div><p class="no_margin"><sup>b</sup>Separate stage groupings are recommended for papillary or follicular (differentiated), medullary, and anaplastic (undifferentiated) carcinoma.</p></div></dd><dt></dt><dd><div><p class="no_margin"><sup>c</sup>All anaplastic carcinomas are considered Stage IV.</p></div></dd></dl></div></div></div></div><div id="CDR0000062913__177"><h3>Papillary and Follicular Thyroid Cancer</h3><p id="CDR0000062913__191"><b><div class="milestone-start" id="CDR0000062913__41"></div>Stage I papillary thyroid cancer</b></p><p id="CDR0000062913__42">Stage I papillary carcinoma is localized to the thyroid gland. In as many as
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50% of cases, there are multifocal sites of papillary adenocarcinomas throughout
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the gland. Most papillary cancers have some follicular elements, and these may
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sometimes be more numerous than the papillary formations, but this does not
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change the prognosis. The 10-year survival rate is slightly better for
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patients younger than 45 years than for patients older than 45 years.
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<div class="milestone-end"></div></p><p id="CDR0000062913__192"><b><div class="milestone-start" id="CDR0000062913__43"></div>Stage II papillary thyroid cancer</b></p><p id="CDR0000062913__44">Stage II papillary carcinoma is defined as either: (1) tumor that has spread
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distantly in patients younger than 45 years, or (2) tumor that is larger than 2 cm but 4 cm or smaller and is limited to the thyroid gland in patients older
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than 45 years. In as many as 50% to 80% of cases, there are multifocal
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sites of papillary adenocarcinomas throughout the gland. Most papillary
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cancers have some follicular elements, and these may sometimes be more numerous
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than the papillary formations, but this does not appear to change the
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prognosis.
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<div class="milestone-end"></div></p><p id="CDR0000062913__193"><b><div class="milestone-start" id="CDR0000062913__45"></div>Stage III papillary thyroid cancer</b></p><p id="CDR0000062913__46">Stage III is papillary carcinoma in patients older than 45 years that is larger than 4 cm and is limited to the thyroid or with minimal extrathyroid extension, or positive lymph nodes limited to the pretracheal, paratracheal, or prelaryngeal/Delphian nodes. Papillary carcinoma that has
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invaded adjacent cervical tissue has a worse prognosis than tumors confined to
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the thyroid.
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<div class="milestone-end"></div></p><p id="CDR0000062913__194"><b><div class="milestone-start" id="CDR0000062913__47"></div>Stage IV papillary thyroid cancer</b></p><p id="CDR0000062913__48">Stage IV is papillary carcinoma in patients older than 45 years with
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extension beyond the thyroid capsule to the soft tissues of the neck, cervical lymph node metastases, or distant metastases. The lungs and bone are the most frequent distant sites of
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spread, though such distant spread is rare in this type of thyroid cancer.
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Papillary carcinoma more frequently metastasizes to regional lymph nodes than
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to distant sites. The prognosis for patients with distant metastases is poor.
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<div class="milestone-end"></div></p><p id="CDR0000062913__195"><b><div class="milestone-start" id="CDR0000062913__49"></div>Stage I follicular thyroid cancer</b></p><p id="CDR0000062913__50">Stage I follicular carcinoma is localized to the thyroid gland. Follicular
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thyroid carcinoma must be distinguished from follicular adenomas, which are
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characterized by their lack of invasion through the capsule into the
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surrounding thyroid tissue. While follicular cancer has a good prognosis, it
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is less favorable than that of papillary carcinoma. The 10-year survival is better for
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patients with follicular carcinoma without vascular invasion than it is for
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patients with vascular invasion.
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<div class="milestone-end"></div></p><p id="CDR0000062913__196"><b><div class="milestone-start" id="CDR0000062913__51"></div>Stage II follicular thyroid cancer</b></p><p id="CDR0000062913__52">Stage II follicular carcinoma is defined as either tumor that has spread
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distantly in patients younger than 45 years, or tumor that is larger than 2 cm but 4 cm or smaller and is limited to the thyroid gland in patients older
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than 45 years. The presence of lymph node metastases does not worsen
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the prognosis among patients younger than 45 years. Follicular thyroid carcinoma must be distinguished from
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follicular adenomas, which are characterized by their lack of invasion through
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the capsule into the surrounding thyroid tissue. While follicular cancer has
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a good prognosis, it is less favorable than that of papillary carcinoma; the
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10-year survival is better for patients with follicular carcinoma without vascular
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invasion than for patients with vascular invasion.
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<div class="milestone-end"></div></p><p id="CDR0000062913__197"><b><div class="milestone-start" id="CDR0000062913__53"></div>Stage III follicular thyroid cancer</b></p><p id="CDR0000062913__54">Stage III is follicular carcinoma in patients older than 45 years, larger than 4 cm and limited to the thyroid or with minimal extrathyroid extension, or positive lymph nodes limited to the pretracheal, paratracheal, or prelaryngeal/Delphian nodes. Follicular carcinoma invading
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cervical tissue has a worse prognosis than tumors confined to the thyroid
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gland. The presence of vascular invasion is an additional poor prognostic
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factor. Metastases to lymph nodes do not worsen the prognosis in patients younger than 45 years.
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<div class="milestone-end"></div></p><p id="CDR0000062913__198"><b><div class="milestone-start" id="CDR0000062913__55"></div>Stage IV follicular thyroid cancer</b></p><p id="CDR0000062913__56">Stage IV is follicular carcinoma in patients older than 45 years with
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extension beyond the thyroid capsule to the soft tissues of the neck, cervical lymph node metastases, or distant metastases. The lungs and bone are the most frequent sites of spread.
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Follicular carcinomas more commonly have blood vessel invasion and tend to
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metastasize hematogenously to the lungs and to the bone rather than through the
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lymphatic system. The prognosis for patients with distant metastases is poor.
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<div class="milestone-end"></div></p><p id="CDR0000062913__257"><b><div class="milestone-start" id="CDR0000062913__256"></div>Hürthle cell carcinoma</b></p><p id="CDR0000062913__258">Hürthle cell carcinoma is a variant of follicular carcinoma with a similar prognosis and should be treated in the same way as equivalent stage non-Hürthle cell follicular carcinoma.<div class="milestone-end"></div>[<a class="bk_pop" href="#CDR0000062913_rl_14_2">2</a>]</p></div><div id="CDR0000062913__57"><h3>Medullary Thyroid Cancer</h3><p id="CDR0000062913__58">Several staging systems have been employed to correlate extent of disease with
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long-term survival in medullary thyroid cancer. The clinical staging system of
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the AJCC correlates survival to size of the primary tumor, presence or absence
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of lymph node metastases, and presence or absence of distance metastasis.
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Patients with the best prognosis are those who are diagnosed by provocative
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screening, prior to the appearance of palpable disease.[<a class="bk_pop" href="#CDR0000062913_rl_14_3">3</a>]
|
|
</p><p id="CDR0000062913__224"><b><div class="milestone-start" id="CDR0000062913__223"></div>Stage 0 medullary thyroid cancer</b></p><p id="CDR0000062913__225">Clinically occult disease detected by provocative biochemical screening.<div class="milestone-end"></div></p><p id="CDR0000062913__199"><b><div class="milestone-start" id="CDR0000062913__160"></div>Stage I medullary thyroid cancer</b></p><p id="CDR0000062913__60">Tumor smaller than 2 cm.
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|
<div class="milestone-end"></div></p><p id="CDR0000062913__200"><b><div class="milestone-start" id="CDR0000062913__161"></div>Stage II medullary thyroid cancer</b></p><p id="CDR0000062913__62">Tumor larger than 2 cm but 4 cm or smaller with no metastases or larger than 4 cm with minimal extrathyroid extension.
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|
<div class="milestone-end"></div></p><p id="CDR0000062913__201"><b><div class="milestone-start" id="CDR0000062913__162"></div>Stage III medullary thyroid cancer</b></p><p id="CDR0000062913__64">Tumor of any size with metastases limited to the pretracheal, paratracheal, or prelaryngeal/Delphian lymph nodes.
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|
<div class="milestone-end"></div></p><p id="CDR0000062913__202"><b><div class="milestone-start" id="CDR0000062913__163"></div>Stage IV medullary thyroid cancer</b></p><p id="CDR0000062913__226">Stage IV medullary thyroid cancer is divided into the following categories:</p><ul id="CDR0000062913__239"><li class="half_rhythm"><div>Stage IVA (moderately advanced with or without lymph node metastases [for T4a] but without distant metastases).</div></li><li class="half_rhythm"><div>Stage IVB (very advanced with or without lymph node metastases but no distant metastases).</div></li><li class="half_rhythm"><div>Stage IVC (distant metastases).<div class="milestone-end"></div></div></li></ul><p id="CDR0000062913__67">Medullary carcinoma usually presents as a hard mass and is often accompanied
|
|
by blood vessel invasion. Medullary thyroid cancer occurs in two forms,
|
|
sporadic and familial. In the sporadic form, the tumor is usually unilateral.
|
|
In the familial form, the tumor is almost always bilateral. In addition, the
|
|
familial form may be associated with benign or malignant tumors of other
|
|
endocrine organs, commonly referred to as the multiple endocrine neoplasia
|
|
syndromes (MEN 2A or MEN 2B).
|
|
</p><p id="CDR0000062913__68">In these syndromes, there is an association with pheochromocytoma of the adrenal
|
|
gland and parathyroid hyperplasia. Medullary carcinoma usually secretes
|
|
calcitonin, a hormonal marker for the tumor, and may be detectable in blood
|
|
even when the tumor is clinically occult. Metastases to regional lymph nodes
|
|
are found in about 50% of cases. Prognosis depends on extent of disease at
|
|
presentation, presence or absence of regional lymph node metastases, and
|
|
completeness of the surgical resection.[<a class="bk_pop" href="#CDR0000062913_rl_14_4">4</a>]</p><p id="CDR0000062913__69">Family members should be screened for calcitonin elevation to identify
|
|
individuals who are at risk of developing familial medullary thyroid cancer.
|
|
MEN 2A gene carrier status can be more accurately determined by analysis of
|
|
mutations in the <i>RET</i> gene. Whereas modest el
|
|
mutation is the optimal approach in evaluating MEN 2A. All patients with
|
|
medullary carcinoma of the thyroid (whether familial or sporadic) should be
|
|
tested for <i>RET</i> mutations, and, if they are positive, family members should
|
|
also be tested. Family members who are gene carriers should undergo
|
|
prophylactic thyroidectomy at an early age.[<a class="bk_pop" href="#CDR0000062913_rl_14_5">5</a>-<a class="bk_pop" href="#CDR0000062913_rl_14_7">7</a>]
|
|
</p></div><div id="CDR0000062913__70"><h3>Anaplastic Thyroid Cancer</h3><p id="CDR0000062913__71">No generally accepted staging system is available for anaplastic thyroid cancer.
|
|
All patients are considered to have stage IV disease.
|
|
</p><p id="CDR0000062913__72">Undifferentiated (anaplastic) carcinomas are highly malignant cancers of
|
|
the thyroid. They may be subclassified as small cell or large cell carcinomas.
|
|
Both grow rapidly and extend to structures beyond the thyroid. Both small cell
|
|
and large cell carcinomas present as hard, ill-defined masses, often with
|
|
extension into the structures surrounding the thyroid. Small cell anaplastic
|
|
thyroid carcinoma must be carefully distinguished from lymphoma. This tumor
|
|
usually occurs in an older age group and is characterized by extensive local
|
|
invasion and rapid progression. Five-year survival with this tumor is poor.
|
|
Death is usually from uncontrolled local cancer in the neck, usually within
|
|
months of diagnosis.[<a class="bk_pop" href="#CDR0000062913_rl_14_8">8</a>]
|
|
</p></div><div id="CDR0000062913_rl_14"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062913_rl_14_1">Thyroid. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 87-96.</div></li><li><div class="bk_ref" id="CDR0000062913_rl_14_2">Haigh PI, Urbach DR: The treatment and prognosis of Hürthle cell follicular thyroid carcinoma compared with its non-Hürthle cell counterpart. Surgery 138 (6): 1152-7; discussion 1157-8, 2005. [<a href="https://pubmed.ncbi.nlm.nih.gov/16360403" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16360403</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_14_3">Colson YL, Carty SE: Medullary thyroid carcinoma. Am J Otolaryngol 14 (2): 73-81, 1993 Mar-Apr. [<a href="https://pubmed.ncbi.nlm.nih.gov/8097904" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8097904</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_14_4">Carling T, Udelsman R: Thyroid tumors. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1457-72.</div></li><li><div class="bk_ref" id="CDR0000062913_rl_14_5">Lips CJ, Landsvater RM, Höppener JW, et al.: Clinical screening as compared with DNA analysis in families with multiple endocrine neoplasia type 2A. N Engl J Med 331 (13): 828-35, 1994. [<a href="https://pubmed.ncbi.nlm.nih.gov/7915822" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7915822</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_14_6">Decker RA, Peacock ML, Borst MJ, et al.: Progress in genetic screening of multiple endocrine neoplasia type 2A: is calcitonin testing obsolete? Surgery 118 (2): 257-63; discussion 263-4, 1995. [<a href="https://pubmed.ncbi.nlm.nih.gov/7638742" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7638742</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_14_7">Skinner MA, Moley JA, Dilley WG, et al.: Prophylactic thyroidectomy in multiple endocrine neoplasia type 2A. N Engl J Med 353 (11): 1105-13, 2005. [<a href="https://pubmed.ncbi.nlm.nih.gov/16162881" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16162881</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_14_8">Neff RL, Farrar WB, Kloos RT, et al.: Anaplastic thyroid cancer. Endocrinol Metab Clin North Am 37 (2): 525-38, xi, 2008. [<a href="https://pubmed.ncbi.nlm.nih.gov/18502341" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18502341</span></a>]</div></li></ol></div></div><div id="CDR0000062913__75"><h2 id="_CDR0000062913__75_">Stage I and II Papillary and Follicular Thyroid Cancer</h2><p id="CDR0000062913__76">Surgery is the therapy of choice for all primary lesions. Surgical options
|
|
include total thyroidectomy or lobectomy. The choice of procedure is
|
|
influenced mainly by the age of the patient and the size of the nodule.
|
|
Survival results may be similar; the difference between them lies in the rates
|
|
of surgical complications and local recurrences.[<a class="bk_pop" href="#CDR0000062913_rl_75_1">1</a>-<a class="bk_pop" href="#CDR0000062913_rl_75_7">7</a>]
|
|
</p><p id="CDR0000062913__77"><b>Standard treatment options:</b>
|
|
</p><ol id="CDR0000062913__164"><li class="half_rhythm"><div><a href="#CDR0000062913__348">Total thyroidectomy</a>.
|
|
</div></li><li class="half_rhythm"><div><a href="#CDR0000062913__354">Lobectomy</a>.</div></li></ol><div id="CDR0000062913__348"><h3>Total Thyroidectomy</h3><p id="CDR0000062913__349">This procedure is advocated because of the high
|
|
incidence of multicentric involvement of both lobes of the gland and the
|
|
possibility of dedifferentiation of any residual tumor to the anaplastic cell
|
|
type. </p><p id="CDR0000062913__350">From the National Cancer Center Data Base (NCDB) registry of 52,173 patients, 43,227 (82.9%) underwent total thyroidectomy, and 8,946 (17.1%) underwent lobectomy. For a papillary thyroid cancer measuring less than 1 cm, the extent of surgery did not impact recurrence or survival (<i>P</i> = .24 and <i>P</i> = .83, respectively).[<a class="bk_pop" href="#CDR0000062913_rl_75_8">8</a>] For tumors measuring 1 cm or larger, lobectomy resulted in higher risk of recurrence and death (<i>P</i> = .04 and <i>P</i> = .009, respectively). To minimize the influence of larger tumors, 1-cm to 2-cm lesions were examined separately; lobectomy again resulted in a higher risk of recurrence and death (<i>P</i> = .04 and <i>P</i> = .04, respectively). In this study, total thyroidectomy resulted in lower recurrence rates and improved survival for patients with papillary thyroid cancer measuring 1 cm or larger compared with lobectomy.[<a class="bk_pop" href="#CDR0000062913_rl_75_8">8</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335144/" class="def">Level of evidence: 3iiA</a>] </p><p id="CDR0000062913__351"> Furthermore, in a pattern of care study, using the NCDB registry from 1985 to 2003, 57,243 papillary thyroid cancer patients with tumors measuring 1 cm or larger underwent total thyroidectomy or lobectomy. Trends in the extent of surgery were examined for patients with papillary thyroid cancer over 2 decades. Logistic regression was used to identify factors that predict the use of total thyroidectomy compared with lobectomy. Use of total thyroidectomy increased from 70.8% in 1985 to 90.4% in 2003 (<i>P</i> < .0001). Patients treated at high-volume medical facilities or academic centers were more likely to undergo total thyroidectomy than were patients examined at low-volume medical facilities or community hospitals (<i>P</i> < .0001).[<a class="bk_pop" href="#CDR0000062913_rl_75_9">9</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000641570/" class="def">Level of evidence: 3i</a>]</p><p id="CDR0000062913__352">The objective of surgery is to completely remove the primary tumor, while minimizing treatment-related morbidity, and to guide postoperative treatment with radioactive iodine (RAI). The goal of RAI is to ablate the remnant thyroid tissue to improve the specificity of thyroglobulin assays, which allows the detection of persistent disease by follow-up whole-body scanning. For patients undergoing RAI, removal of all normal thyroid tissue is an important surgical objective. Additionally, for accurate long-term surveillance, RAI whole-body scanning and measurement of serum thyroglobulin are affected by residual, normal thyroid tissue, and in these situations, near total or total thyroidectomy is required. This approach facilitates follow-up thyroid scanning. </p><p id="CDR0000062913__353"><b>I<sup>131</sup>:</b> Studies have shown that a postoperative course of therapeutic
|
|
(ablative) doses of I<sup>131</sup> results in a decreased recurrence rate among high-risk patients with papillary
|
|
and follicular carcinomas.[<a class="bk_pop" href="#CDR0000062913_rl_75_4">4</a>] It may be given in addition to exogenous thyroid
|
|
hormone but is not considered routine.[<a class="bk_pop" href="#CDR0000062913_rl_75_10">10</a>] Patients presenting with papillary
|
|
thyroid microcarcinomas (tumors <10 mm) have an excellent prognosis when
|
|
treated surgically, and additional therapy with I<sup>131</sup> would not be expected to
|
|
improve the prognosis.[<a class="bk_pop" href="#CDR0000062913_rl_75_11">11</a>]</p></div><div id="CDR0000062913__354"><h3>Lobectomy</h3><p id="CDR0000062913__355">Thyroid lobectomy alone may be sufficient treatment for small (<1 cm), low-risk, unifocal, intrathyroidal papillary carcinomas in the absence of prior head and neck irradiation or radiologically or clinically involved cervical nodal metastases. This procedure is associated with a lower incidence of
|
|
complications, but approximately 5% to 10% of patients will have a recurrence
|
|
in the thyroid following lobectomy.[<a class="bk_pop" href="#CDR0000062913_rl_75_12">12</a>] Patients younger than 45 years will have the longest follow-up period and the greatest opportunity for
|
|
recurrence. Follicular thyroid cancer commonly metastasizes to lungs and bone; with a remnant lobe in place, use of I<sup>131</sup> as ablative therapy is compromised. Abnormal regional lymph nodes should be biopsied at the time of
|
|
surgery. Recognized nodal involvement should be removed at initial surgery, but
|
|
selective node removal can be performed, and radical neck dissection is usually not
|
|
required.
|
|
This
|
|
results in a decreased recurrence rate but has not been shown to improve
|
|
survival.
|
|
</p><p id="CDR0000062913__356">Following the surgical procedure, patients should receive postoperative
|
|
treatment with exogenous thyroid hormone in doses sufficient to suppress
|
|
thyroid-stimulating hormone (TSH); studies have shown a decreased incidence of
|
|
recurrence when TSH is suppressed.</p><p id="CDR0000062913__383"><b>I<sup>131</sup>:</b> Studies have shown that a postoperative course of therapeutic
|
|
(ablative) doses of I<sup>131</sup> results in a decreased recurrence rate among high-risk patients with papillary
|
|
and follicular carcinomas.[<a class="bk_pop" href="#CDR0000062913_rl_75_4">4</a>] For optimal treatment with RAI, total thyroidectomy is recommended with minimal thyroid remnant remaining. With a large thyroid remnant, a low thyroglobulin level cannot be achieved, which increases the chance of requiring multiple doses of RAI. </p><p id="CDR0000062913__384">Consideration of RAI for remnant ablation is based on pathological risk features including: </p><ul id="CDR0000062913__385"><li class="half_rhythm"><div>Evaluation of the size of the primary tumor.</div></li><li class="half_rhythm"><div>The presence of lymphovascular invasion.</div></li><li class="half_rhythm"><div>Capsule invasion.</div></li><li class="half_rhythm"><div>The number of involved lymph nodes.</div></li></ul><p id="CDR0000062913__357"> RAI may be given with one of two methods of thyrotropin stimulation: withdrawal of thyroid hormone or recombinant human thyrotropin (rhTSH). Administered rhTSH maintains quality of life and reduces the radiation dose delivered to the body compared with thyroid hormone withdrawal.[<a class="bk_pop" href="#CDR0000062913_rl_75_13">13</a>] Patients presenting with papillary
|
|
thyroid microcarcinomas (tumors <10 mm), which are considered to be very low risk, have an excellent prognosis when
|
|
treated surgically, and additional therapy with I<sup>131</sup> would not be expected to
|
|
improve the prognosis.[<a class="bk_pop" href="#CDR0000062913_rl_75_11">11</a>]</p><p id="CDR0000062913__358">The role of RAI in low-risk patients is not clear because disease-free survival (DFS) or overall survival (OS) benefits have not been demonstrated. One study reviewed 1,298 patients from the French Thyroid Cancer Registry.[<a class="bk_pop" href="#CDR0000062913_rl_75_14">14</a>] Patients were identified as having low-risk papillary or follicular cancer as they are defined by the American Thyroid Association and the European Thyroid Association criteria: </p><ul id="CDR0000062913__359"><li class="half_rhythm"><div>Complete tumor resection. </div></li><li class="half_rhythm"><div>Multifocal pT1 <1 cm. </div></li><li class="half_rhythm"><div>pT1 >1 cm. </div></li><li class="half_rhythm"><div> pT2, pN0, pM0 (American Joint Committee on Cancer/Union Internationale Contre le Cancer [AJCC/UICC]) corresponds to stage I for patients younger than 45 years.</div></li><li class="half_rhythm"><div> pT2, pN0, pM0 (AJCC/UICC) corresponds to stages 1 and 2 for patients older than 45 years.</div></li><li class="half_rhythm"><div>pT1 and pT2 without lymph node dissection (Nx). </div></li></ul><p id="CDR0000062913__360"> Of the 1,298 patients, 911 patients received RAI after surgery, and 387 patients did not receive RAI after surgery. Follow-up period was 10.3 years; in multivariate analyses, there were no differences in OS (<i>P</i> = .243) or DFS (<i>P</i> = .2659), according to RAI use.[<a class="bk_pop" href="#CDR0000062913_rl_75_14">14</a>]</p><p id="CDR0000062913__361">Long-term complications of RAI using I<sup>131</sup> include second malignancies, sialadenitis, and lacrimal and salivary gland dysfunction. Options for reducing the amount of radiation exposure by reducing the amount of RAI in each dose and also to give RAI in combination with rhTSH injections have been explored for low-risk thyroid cancer patients. </p><p id="CDR0000062913__362">Two phase III, randomized, noninferiority studies of patients with low-risk thyroid cancer using a comparison of two thyrotropin-stimulation methods (thyroid hormone withdrawal or use of rhTSH) and two doses of radioiodine I<sup>131</sup> 1.1GBq [30mCi] and 3.7GBq [100mCi] using a 2 × 2 factorial design showed equivalent thyroid ablation rates between high and low dose I<sup>131</sup> at 6 to 10 months after administration of I<sup>131</sup>.[<a class="bk_pop" href="#CDR0000062913_rl_75_15">15</a>,<a class="bk_pop" href="#CDR0000062913_rl_75_16">16</a>][Levels of evidence: <a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335138/" class="def">3iA</a> and <a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335142/" class="def">3iDii</a>] However, differences in the inclusion criteria in one study [<a class="bk_pop" href="#CDR0000062913_rl_75_15">15</a>] consisted of a low-risk, homogeneous cohort in which all of the patients underwent total thyroidectomy, and had pathological TNM stage pT1 ( ≤1 cm) and N1 or Nx, pT1 (>1–2cm) and any N stage, or pT2N0 without thyroid capsule extension/distant metastases. Complete thyroid ablation rate in this study was 92%. Patients undergoing thyroid hormone withdrawal had greater symptoms of hypothyroidism associated with deterioration in quality of life compared with the rhTSH group. </p><p id="CDR0000062913__363">In the other study,[<a class="bk_pop" href="#CDR0000062913_rl_75_16">16</a>] patients with more advanced T stage (T1–T3, N0–1) and with less than a total thyroidectomy were included with a lower overall ablation rate of 85%. Neither study assessed the effect of low-dose RAI on long-term recurrences or survival. The studies also did not address whether RAI could be safely omitted in specific low-risk groups. </p></div><div id="CDR0000062913__TrialSearch_75_sid_4"><h3>Current Clinical Trials</h3><p id="CDR0000062913__TrialSearch_75_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=38802&tt=1&format=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">stage I papillary thyroid cancer</a>, <a href="http://www.cancer.gov/search/ClinicalTrialsLink.aspx?Diagnosis=38805&tt=1&format=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">stage I follicular thyroid cancer</a>, <a href="http://www.cancer.gov/search/ClinicalTrialsLink.aspx?Diagnosis=38803&tt=1&format=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">stage II papillary thyroid cancer</a> and <a href="http://www.cancer.gov/search/ClinicalTrialsLink.aspx?Diagnosis=38806&tt=1&format=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">stage II follicular thyroid cancer</a>. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.</p><p id="CDR0000062913__TrialSearch_75_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="CDR0000062913_rl_75"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062913_rl_75_1">Carling T, Udelsman R: Thyroid tumors. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1457-72.</div></li><li><div class="bk_ref" id="CDR0000062913_rl_75_2">Grant CS, Hay ID, Gough IR, et al.: Local recurrence in papillary thyroid carcinoma: is extent of surgical resection important? Surgery 104 (6): 954-62, 1988. [<a href="https://pubmed.ncbi.nlm.nih.gov/3194847" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3194847</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_75_3">Cady B, Rossi R: An expanded view of risk-group definition in differentiated thyroid carcinoma. Surgery 104 (6): 947-53, 1988. [<a href="https://pubmed.ncbi.nlm.nih.gov/3194846" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3194846</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_75_4">Mazzaferri EL, Jhiang SM: Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med 97 (5): 418-28, 1994. [<a href="https://pubmed.ncbi.nlm.nih.gov/7977430" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7977430</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_75_5">Staunton MD: Thyroid cancer: a multivariate analysis on influence of treatment on long-term survival. Eur J Surg Oncol 20 (6): 613-21, 1994. [<a href="https://pubmed.ncbi.nlm.nih.gov/7995409" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7995409</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_75_6">Tollefsen HR, Shah JP, Huvos AG: Follicular carcinoma of the thyroid. Am J Surg 126 (4): 523-8, 1973. [<a href="https://pubmed.ncbi.nlm.nih.gov/4743837" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 4743837</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_75_7">Edis AJ: Surgical treatment for thyroid cancer. Surg Clin North Am 57 (3): 533-42, 1977. [<a href="https://pubmed.ncbi.nlm.nih.gov/867221" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 867221</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_75_8">Bilimoria KY, Bentrem DJ, Ko CY, et al.: Extent of surgery affects survival for papillary thyroid cancer. Ann Surg 246 (3): 375-81; discussion 381-4, 2007. [<a href="/pmc/articles/PMC1959355/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1959355</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/17717441" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17717441</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_75_9">Bilimoria KY, Bentrem DJ, Linn JG, et al.: Utilization of total thyroidectomy for papillary thyroid cancer in the United States. Surgery 142 (6): 906-13; discussion 913.e1-2, 2007. [<a href="https://pubmed.ncbi.nlm.nih.gov/18063075" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18063075</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_75_10">Beierwaltes WH, Rabbani R, Dmuchowski C, et al.: An analysis of "ablation of thyroid remnants" with I-131 in 511 patients from 1947-1984: experience at University of Michigan. J Nucl Med 25 (12): 1287-93, 1984. [<a href="https://pubmed.ncbi.nlm.nih.gov/6502251" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6502251</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_75_11">Hay ID, Grant CS, van Heerden JA, et al.: Papillary thyroid microcarcinoma: a study of 535 cases observed in a 50-year period. Surgery 112 (6): 1139-46; discussion 1146-7, 1992. [<a href="https://pubmed.ncbi.nlm.nih.gov/1455316" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1455316</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_75_12">Hay ID, Grant CS, Bergstralh EJ, et al.: Unilateral total lobectomy: is it sufficient surgical treatment for patients with AMES low-risk papillary thyroid carcinoma? Surgery 124 (6): 958-64; discussion 964-6, 1998. [<a href="https://pubmed.ncbi.nlm.nih.gov/9854569" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9854569</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_75_13">Hänscheid H, Lassmann M, Luster M, et al.: Iodine biokinetics and dosimetry in radioiodine therapy of thyroid cancer: procedures and results of a prospective international controlled study of ablation after rhTSH or hormone withdrawal. J Nucl Med 47 (4): 648-54, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/16595499" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16595499</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_75_14">Schvartz C, Bonnetain F, Dabakuyo S, et al.: Impact on overall survival of radioactive iodine in low-risk differentiated thyroid cancer patients. J Clin Endocrinol Metab 97 (5): 1526-35, 2012. [<a href="https://pubmed.ncbi.nlm.nih.gov/22344193" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22344193</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_75_15">Schlumberger M, Catargi B, Borget I, et al.: Strategies of radioiodine ablation in patients with low-risk thyroid cancer. N Engl J Med 366 (18): 1663-73, 2012. [<a href="https://pubmed.ncbi.nlm.nih.gov/22551127" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22551127</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_75_16">Mallick U, Harmer C, Yap B, et al.: Ablation with low-dose radioiodine and thyrotropin alfa in thyroid cancer. N Engl J Med 366 (18): 1674-85, 2012. [<a href="https://pubmed.ncbi.nlm.nih.gov/22551128" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22551128</span></a>]</div></li></ol></div></div><div id="CDR0000062913__103"><h2 id="_CDR0000062913__103_">Stage III Papillary and Follicular Thyroid Cancer</h2><p id="CDR0000062913__104"><b>Standard treatment options:</b>
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</p><ol id="CDR0000062913__168"><li class="half_rhythm"><div>Total thyroidectomy plus removal of involved lymph nodes or other sites of extrathyroid disease.</div></li><li class="half_rhythm"><div>I<sup>131</sup> ablation following total thyroidectomy if the tumor demonstrates
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uptake of this isotope.[<a class="bk_pop" href="#CDR0000062913_rl_103_1">1</a>]</div></li><li class="half_rhythm"><div>External-beam radiation therapy if I<sup>131</sup> uptake is minimal.[<a class="bk_pop" href="#CDR0000062913_rl_103_2">2</a>]
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</div></li></ol><div id="CDR0000062913__TrialSearch_103_sid_5"><h3>Current Clinical Trials</h3><p id="CDR0000062913__TrialSearch_103_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=39305&tt=1&format=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">stage III papillary thyroid cancer</a> and <a href="http://www.cancer.gov/search/ClinicalTrialsLink.aspx?Diagnosis=39304&tt=1&format=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">stage III follicular thyroid cancer</a>. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.</p><p id="CDR0000062913__TrialSearch_103_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="CDR0000062913_rl_103"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062913_rl_103_1">Beierwaltes WH, Rabbani R, Dmuchowski C, et al.: An analysis of "ablation of thyroid remnants" with I-131 in 511 patients from 1947-1984: experience at University of Michigan. J Nucl Med 25 (12): 1287-93, 1984. [<a href="https://pubmed.ncbi.nlm.nih.gov/6502251" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6502251</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_103_2">Simpson WJ, Carruthers JS: The role of external radiation in the management of papillary and follicular thyroid cancer. Am J Surg 136 (4): 457-60, 1978. [<a href="https://pubmed.ncbi.nlm.nih.gov/707725" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 707725</span></a>]</div></li></ol></div></div><div id="CDR0000062913__113"><h2 id="_CDR0000062913__113_">Stage IV Papillary and Follicular Thyroid Cancer</h2><p id="CDR0000062913__114">The most common sites of metastases are lymph nodes, lung, and bone. Treatment
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of lymph node metastases alone is often curative. Treatment of distant
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metastases is usually not curative but may produce significant palliation.
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</p><p id="CDR0000062913__115"><b>Standard treatment options for iodine-sensitive thyroid cancer:</b>
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</p><ul id="CDR0000062913__392"><li class="half_rhythm"><div> I<sup>131</sup>: Metastases that demonstrate uptake of this isotope may be ablated
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by therapeutic doses of I<sup>131</sup>.</div></li></ul><p id="CDR0000062913__393"><b>Standard treatment options for iodine-resistant thyroid cancer:</b></p><ol id="CDR0000062913__170"><li class="half_rhythm"><div>Thyroid-stimulating hormone suppression with thyroxine is effective in many
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lesions not sensitive to I<sup>131</sup>.</div></li><li class="half_rhythm"><div>Sorafenib: A phase III randomized, double-blind, placebo-controlled study (<a href="http://cancer.gov/clinicaltrials/search/view?version=healthprofessional&cdrid=656501" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">DECISION</a> [<a href="https://clinicaltrials.gov/show/NCT00984282" title="Study NCT00984282" ref="pagearea=body&targetsite=external&targetcat=link&targettype=clinical-trial">NCT00984282</a>]) evaluated the activity of sorafenib, an orally active, multityrosine kinase inhibitor, in patients with progressive iodine-refractory differentiated thyroid cancer.[<a class="bk_pop" href="#CDR0000062913_rl_113_1">1</a>] In the trial, 417 patients with locally advanced or metastatic radioactive iodine-refractory thyroid cancer (papillary, follicular [including Hürthle cell], and poorly differentiated varieties) who had progressed within the past 14 months were randomly assigned to sorafenib (400 mg twice daily) versus placebo. Prior chemotherapy, thalidomide, or targeted therapy were excluded.[<a class="bk_pop" href="#CDR0000062913_rl_113_1">1</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335124/" class="def">Level of evidence: 1iDiii</a>]<ul id="CDR0000062913__390"><li class="half_rhythm"><div> The median progression-free survival in the sorafenib versus placebo groups was 10.8 versus 5.8 months (hazard ratio (HR), 0.59; 95% confidence interval (CI), 0.45–0.76; <i>P </i>< .001). </div></li><li class="half_rhythm"><div> Overall survival (OS) was not significantly improved (HR, 0.80; 95% CI, 0.54–1.19; <i>P</i> = .14, one-sided <i>P</i>-value), but the median OS had not been reached at the time of primary analysis data cutoff and crossover was allowed. </div></li><li class="half_rhythm"><div> Objective response rates (all partial) were 12.2% in the sorafenib group compared with 0.5% in the placebo group. Median time-to-progression was 11.1 months in the sorafenib group compared with 5.7 months in the placebo group (HR, 0.56; 95% CI, 0.43–0.72; <i>P</i> < .001). </div></li><li class="half_rhythm"><div> Adverse events (AEs) occurred in 98.6% of patients treated with sorafenib and 87.6% of patients treated with placebo. The most frequent AEs in the sorafenib group were hand-foot skin reactions (76.3%), diarrhea (68.6%), alopecia (67.1%), and rash or desquamation (50.2%). Most events were grade 1 or 2 in severity. Seven squamous cell carcinomas of the skin occurred in the sorafenib group.</div></li></ul></div></li><li class="half_rhythm"><div>Resection of limited metastases, especially symptomatic metastases, should be considered when the tumor has no uptake of I<sup>131</sup>.</div></li><li class="half_rhythm"><div>External-beam radiation therapy for patients with localized lesions that are
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|
unresponsive to I<sup>131</sup>.[<a class="bk_pop" href="#CDR0000062913_rl_113_2">2</a>]</div></li></ol><p id="CDR0000062913__241">Patients unresponsive to I<sup>131</sup> should also be considered candidates for
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clinical trials testing new approaches to this disease.</p><p id="CDR0000062913__121"><b>Treatment options under clinical evaluation:</b>
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|
</p><ul id="CDR0000062913__171"><li class="half_rhythm"><div>Clinical trials evaluating new treatment approaches to this disease should also
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|
be considered for these patients. Chemotherapy has been reported to produce
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|
occasional complete responses of long duration.[<a class="bk_pop" href="#CDR0000062913_rl_113_3">3</a>-<a class="bk_pop" href="#CDR0000062913_rl_113_5">5</a>] Oral inhibitors of vascular endothelial growth-factor receptors are under clinical evaluation.[<a class="bk_pop" href="#CDR0000062913_rl_113_6">6</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335136/" class="def">Level of evidence: 2Dii</a>] </div></li></ul><div id="CDR0000062913__TrialSearch_113_sid_6"><h3>Current Clinical Trials</h3><p id="CDR0000062913__TrialSearch_113_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=38804&tt=1&format=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">stage IV papillary thyroid cancer</a> and <a href="http://www.cancer.gov/search/ClinicalTrialsLink.aspx?Diagnosis=38807&tt=1&format=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">stage IV follicular thyroid cancer</a>. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.</p><p id="CDR0000062913__TrialSearch_113_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="CDR0000062913_rl_113"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062913_rl_113_1">Brose MS, Nutting CM, Jarzab B, et al.: Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet 384 (9940): 319-28, 2014. [<a href="/pmc/articles/PMC4366116/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4366116</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24768112" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24768112</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_113_2">Simpson WJ, Carruthers JS: The role of external radiation in the management of papillary and follicular thyroid cancer. Am J Surg 136 (4): 457-60, 1978. [<a href="https://pubmed.ncbi.nlm.nih.gov/707725" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 707725</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_113_3">Gottlieb JA, Hill CS Jr, Ibanez ML, et al.: Chemotherapy of thyroid cancer. An evaluation of experience with 37 patients. Cancer 30 (3): 848-53, 1972. [<a href="https://pubmed.ncbi.nlm.nih.gov/5075365" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 5075365</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_113_4">Harada T, Nishikawa Y, Suzuki T, et al.: Bleomycin treatment for cancer of the thyroid. Am J Surg 122 (1): 53-7, 1971. [<a href="https://pubmed.ncbi.nlm.nih.gov/5091855" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 5091855</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_113_5">Shimaoka K, Schoenfeld DA, DeWys WD, et al.: A randomized trial of doxorubicin versus doxorubicin plus cisplatin in patients with advanced thyroid carcinoma. Cancer 56 (9): 2155-60, 1985. [<a href="https://pubmed.ncbi.nlm.nih.gov/3902203" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3902203</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_113_6">Sherman SI, Wirth LJ, Droz JP, et al.: Motesanib diphosphate in progressive differentiated thyroid cancer. N Engl J Med 359 (1): 31-42, 2008. [<a href="https://pubmed.ncbi.nlm.nih.gov/18596272" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18596272</span></a>]</div></li></ol></div></div><div id="CDR0000062913__132"><h2 id="_CDR0000062913__132_">Medullary Thyroid Cancer</h2><p id="CDR0000062913__133">Medullary thyroid cancer (MTC) comprises 3% to 4% of all thyroid cancers.
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|
These tumors usually present as a mass in the neck or thyroid, often associated
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|
with lymphadenopathy,[<a class="bk_pop" href="#CDR0000062913_rl_132_1">1</a>] or they may be diagnosed through screening family
|
|
members. MTC can also be diagnosed by fine-needle aspiration biopsy. Cytology
|
|
typically reveals hypercellular tumors with spindle-shaped cells and poor
|
|
adhesion.[<a class="bk_pop" href="#CDR0000062913_rl_132_2">2</a>]
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|
</p><p id="CDR0000062913__229">The overall survival of patients with MTC is 86% at 5 years and 65% at 10 years. Poor prognostic
|
|
factors include advanced age, advanced stage, prior neck surgery, and
|
|
associated multiple endocrine neoplasia (MEN) 2B.[<a class="bk_pop" href="#CDR0000062913_rl_132_2">2</a>-<a class="bk_pop" href="#CDR0000062913_rl_132_4">4</a>]</p><p id="CDR0000062913__230">Approximately 25% of reported cases of MTC are familial.
|
|
Familial MTC syndromes include MEN 2A, which is
|
|
the most common; MEN 2B; and familial non-MEN syndromes. (Refer to the PDQ summary on <a href="/books/n/pdqcis/CDR0000062890/">Genetics of Endocrine and Neuroendocrine Neoplasias</a> for more information.) Any patient with a
|
|
familial variant should be screened for other associated endocrine tumors,
|
|
particularly parathyroid hyperplasia and pheochromocytoma. MTC can secrete
|
|
calcitonin and other peptide substances. Determining the level of calcitonin
|
|
is useful for diagnostic purposes and for following the results of treatment.
|
|
</p><p id="CDR0000062913__134">Family members should be screened for calcitonin elevation and/or for the <i>RET</i>
|
|
proto-oncogene mutation to identify other individuals at risk for developing
|
|
familial MTC. All patients with MTC (whether familial or sporadic) should be
|
|
tested for <i>RET</i> mutations, and if they are positive, family members should
|
|
also be tested. Whereas modest elevation of calcitonin may lead to a false-positive diagnosis of medullary carcinoma, DNA testing for the <i>RET</i> mutation is
|
|
the optimal approach. Family members who are gene carriers should undergo
|
|
prophylactic thyroidectomy at an early age.[<a class="bk_pop" href="#CDR0000062913_rl_132_5">5</a>,<a class="bk_pop" href="#CDR0000062913_rl_132_6">6</a>]
|
|
</p><p id="CDR0000062913__231"><b>Treatment options for localized disease:</b></p><ol id="CDR0000062913__232"><li class="half_rhythm"><div><a href="#CDR0000062913__364">Thyroidectomy.</a>
|
|
</div></li><li class="half_rhythm"><div><a href="#CDR0000062913__366">External radiation therapy.</a>
|
|
</div></li></ol><div id="CDR0000062913__364"><h3>Thyroidectomy</h3><p id="CDR0000062913__365">Patients with MTC should be treated with a total
|
|
thyroidectomy, unless there is evidence of distant metastasis. In patients
|
|
with clinically palpable MTC, the incidence of
|
|
microscopically positive nodes is more than 75%; routine central and bilateral
|
|
modified neck dissections have been recommended.[<a class="bk_pop" href="#CDR0000062913_rl_132_7">7</a>] When cancer is confined to
|
|
the thyroid gland, the prognosis is excellent.</p></div><div id="CDR0000062913__366"><h3>External Radiation Therapy</h3><p id="CDR0000062913__367">External radiation therapy has been used for palliation of locally recurrent
|
|
tumors; however, no evidence exists that it provides any survival advantage.[<a class="bk_pop" href="#CDR0000062913_rl_132_8">8</a>] Radioactive iodine has no place in the treatment of patients with MTC.
|
|
</p><p id="CDR0000062913__325"><b>Treatment options for locally advanced and metastatic disease:</b></p><ul id="CDR0000062913__376"><li class="half_rhythm"><div><a href="#CDR0000062913__370">Palliative chemotherapy</a>.</div></li></ul></div><div id="CDR0000062913__370"><h3>Palliative Chemotherapy</h3><p id="CDR0000062913__371">Vandetanib is an oral inhibitor of RET kinase, vascular endothelial growth-factor receptor, and epidermal growth-factor receptor signaling. It was tested in a placebo-controlled, prospective trial (<a href="http://cancer.gov/clinicaltrials/search/view?version=healthprofessional&cdrid=526877" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCT00410761</a>) in 331 patients with locally advanced and metastatic disease with a 2:1 ratio in assignment to the study drug.[<a class="bk_pop" href="#CDR0000062913_rl_132_9">9</a>] With a median follow-up of 24 months, progression-free survival (PFS) favored vandetanib (hazard ratio = 0.46; 95% confidence interval, 0.31–0.69; <i>P</i> < .001) with a median PFS estimated at 30.5 months for vandetanib versus 19.3 months for placebo.[<a class="bk_pop" href="#CDR0000062913_rl_132_9">9</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335131/" class="def">Level of evidence: 1iiDiii</a>] </p><p id="CDR0000062913__372">Overall survival (OS) was not different at 24 months; longer follow-up will be required since only 47 patients had died at the time of analysis, and there was a crossover to the study drug on progression from placebo, making analysis of OS problematic. Vandetanib has significant side effects, including diarrhea, rash, hypertension, and QT prolongation. Quality of life was not formally assessed in this trial.[<a class="bk_pop" href="#CDR0000062913_rl_132_9">9</a>] </p><p id="CDR0000062913__373">Palliative chemotherapy has been reported to produce occasional responses in
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|
patients with metastatic disease.[<a class="bk_pop" href="#CDR0000062913_rl_132_10">10</a>-<a class="bk_pop" href="#CDR0000062913_rl_132_13">13</a>] No single drug regimen can be
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|
considered standard. Some patients with distant metastases will experience
|
|
prolonged survival and can be managed expectantly until they become
|
|
symptomatic.</p></div><div id="CDR0000062913__TrialSearch_132_sid_7"><h3>Current Clinical Trials</h3><p id="CDR0000062913__TrialSearch_132_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=38808&tt=1&format=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">thyroid gland medullary carcinoma</a>. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.</p><p id="CDR0000062913__TrialSearch_132_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="CDR0000062913_rl_132"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062913_rl_132_1">Soh EY, Clark OH: Surgical considerations and approach to thyroid cancer. Endocrinol Metab Clin North Am 25 (1): 115-39, 1996. [<a href="https://pubmed.ncbi.nlm.nih.gov/8907683" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8907683</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_132_2">Giuffrida D, Gharib H: Current diagnosis and management of medullary thyroid carcinoma. Ann Oncol 9 (7): 695-701, 1998. [<a href="https://pubmed.ncbi.nlm.nih.gov/9739433" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9739433</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_132_3">Saad MF, Ordonez NG, Rashid RK, et al.: Medullary carcinoma of the thyroid. A study of the clinical features and prognostic factors in 161 patients. Medicine (Baltimore) 63 (6): 319-42, 1984. [<a href="https://pubmed.ncbi.nlm.nih.gov/6503683" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6503683</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_132_4">Bergholm U, Bergström R, Ekbom A: Long-term follow-up of patients with medullary carcinoma of the thyroid. Cancer 79 (1): 132-8, 1997. [<a href="https://pubmed.ncbi.nlm.nih.gov/8988737" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8988737</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_132_5">Lips CJ, Landsvater RM, Höppener JW, et al.: Clinical screening as compared with DNA analysis in families with multiple endocrine neoplasia type 2A. N Engl J Med 331 (13): 828-35, 1994. [<a href="https://pubmed.ncbi.nlm.nih.gov/7915822" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7915822</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_132_6">Decker RA, Peacock ML, Borst MJ, et al.: Progress in genetic screening of multiple endocrine neoplasia type 2A: is calcitonin testing obsolete? Surgery 118 (2): 257-63; discussion 263-4, 1995. [<a href="https://pubmed.ncbi.nlm.nih.gov/7638742" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7638742</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_132_7">Moley JF, DeBenedetti MK: Patterns of nodal metastases in palpable medullary thyroid carcinoma: recommendations for extent of node dissection. Ann Surg 229 (6): 880-7; discussion 887-8, 1999. [<a href="/pmc/articles/PMC1420836/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1420836</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/10363903" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10363903</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_132_8">Brierley JD, Tsang RW: External radiation therapy in the treatment of thyroid malignancy. Endocrinol Metab Clin North Am 25 (1): 141-57, 1996. [<a href="https://pubmed.ncbi.nlm.nih.gov/8907684" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8907684</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_132_9">Wells SA Jr, Robinson BG, Gagel RF, et al.: Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol 30 (2): 134-41, 2012. [<a href="/pmc/articles/PMC3675689/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3675689</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22025146" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22025146</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_132_10">Shimaoka K, Schoenfeld DA, DeWys WD, et al.: A randomized trial of doxorubicin versus doxorubicin plus cisplatin in patients with advanced thyroid carcinoma. Cancer 56 (9): 2155-60, 1985. [<a href="https://pubmed.ncbi.nlm.nih.gov/3902203" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3902203</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_132_11">De Besi P, Busnardo B, Toso S, et al.: Combined chemotherapy with bleomycin, adriamycin, and platinum in advanced thyroid cancer. J Endocrinol Invest 14 (6): 475-80, 1991. [<a href="https://pubmed.ncbi.nlm.nih.gov/1723086" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1723086</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_132_12">Wu LT, Averbuch SD, Ball DW, et al.: Treatment of advanced medullary thyroid carcinoma with a combination of cyclophosphamide, vincristine, and dacarbazine. Cancer 73 (2): 432-6, 1994. [<a href="https://pubmed.ncbi.nlm.nih.gov/8293411" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8293411</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_132_13">Orlandi F, Caraci P, Berruti A, et al.: Chemotherapy with dacarbazine and 5-fluorouracil in advanced medullary thyroid cancer. Ann Oncol 5 (8): 763-5, 1994. [<a href="https://pubmed.ncbi.nlm.nih.gov/7826911" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7826911</span></a>]</div></li></ol></div></div><div id="CDR0000062913__139"><h2 id="_CDR0000062913__139_">Anaplastic Thyroid Cancer</h2><p id="CDR0000062913__140"><b>Standard treatment options:
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</b></p><ol id="CDR0000062913__174"><li class="half_rhythm"><div><a href="#CDR0000062913__377">Surgery</a>.</div></li><li class="half_rhythm"><div><a href="#CDR0000062913__379">Radiation therapy</a>.</div></li><li class="half_rhythm"><div><a href="#CDR0000062913__381">Chemotherapy</a>.</div></li></ol><div id="CDR0000062913__377"><h3>Surgery</h3><p id="CDR0000062913__378"> Tracheostomy is frequently necessary. If the disease is confined to the local area, which is rare, total thyroidectomy is warranted to
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reduce symptoms caused by the tumor mass.[<a class="bk_pop" href="#CDR0000062913_rl_139_1">1</a>,<a class="bk_pop" href="#CDR0000062913_rl_139_2">2</a>]</p></div><div id="CDR0000062913__379"><h3>Radiation Therapy</h3><p id="CDR0000062913__380">External-beam radiation therapy may be used in patients who are not surgical candidates or whose tumor cannot be surgically
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excised.
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</p></div><div id="CDR0000062913__381"><h3>Chemotherapy</h3><p id="CDR0000062913__382"> Anaplastic thyroid cancer is not responsive to I<sup>131</sup> therapy;
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treatment with individual anticancer drugs has been reported to produce partial
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remissions in some patients. Approximately 30% of patients achieve a partial
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remission with doxorubicin.[<a class="bk_pop" href="#CDR0000062913_rl_139_3">3</a>] The combination of doxorubicin plus cisplatin
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appears to be more active than doxorubicin alone and has been reported to
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produce more complete responses.[<a class="bk_pop" href="#CDR0000062913_rl_139_4">4</a>]</p><p id="CDR0000062913__144"><b>Treatment options under clinical evaluation:</b>
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</p><ul id="CDR0000062913__175"><li class="half_rhythm"><div>The combination of chemotherapy plus radiation therapy in patients following complete
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resection may provide prolonged survival but has not been compared with any one
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modality alone.[<a class="bk_pop" href="#CDR0000062913_rl_139_5">5</a>,<a class="bk_pop" href="#CDR0000062913_rl_139_6">6</a>] </div></li></ul></div><div id="CDR0000062913__TrialSearch_139_sid_8"><h3>Current Clinical Trials</h3><p id="CDR0000062913__TrialSearch_139_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=38809&tt=1&format=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">anaplastic thyroid cancer</a>. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.</p><p id="CDR0000062913__TrialSearch_139_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="CDR0000062913_rl_139"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062913_rl_139_1">Goldman JM, Goren EN, Cohen MH, et al.: Anaplastic thyroid carcinoma: long-term survival after radical surgery. J Surg Oncol 14 (4): 389-94, 1980. [<a href="https://pubmed.ncbi.nlm.nih.gov/7442263" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7442263</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_139_2">Aldinger KA, Samaan NA, Ibanez M, et al.: Anaplastic carcinoma of the thyroid: a review of 84 cases of spindle and giant cell carcinoma of the thyroid. Cancer 41 (6): 2267-75, 1978. [<a href="https://pubmed.ncbi.nlm.nih.gov/657091" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 657091</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_139_3">Carling T, Udelsman R: Thyroid tumors. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1457-72.</div></li><li><div class="bk_ref" id="CDR0000062913_rl_139_4">Shimaoka K, Schoenfeld DA, DeWys WD, et al.: A randomized trial of doxorubicin versus doxorubicin plus cisplatin in patients with advanced thyroid carcinoma. Cancer 56 (9): 2155-60, 1985. [<a href="https://pubmed.ncbi.nlm.nih.gov/3902203" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3902203</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_139_5">Haigh PI, Ituarte PH, Wu HS, et al.: Completely resected anaplastic thyroid carcinoma combined with adjuvant chemotherapy and irradiation is associated with prolonged survival. Cancer 91 (12): 2335-42, 2001. [<a href="https://pubmed.ncbi.nlm.nih.gov/11413523" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11413523</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_139_6">De Crevoisier R, Baudin E, Bachelot A, et al.: Combined treatment of anaplastic thyroid carcinoma with surgery, chemotherapy, and hyperfractionated accelerated external radiotherapy. Int J Radiat Oncol Biol Phys 60 (4): 1137-43, 2004. [<a href="https://pubmed.ncbi.nlm.nih.gov/15519785" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15519785</span></a>]</div></li></ol></div></div><div id="CDR0000062913__146"><h2 id="_CDR0000062913__146_">Recurrent Thyroid Cancer</h2><p id="CDR0000062913__147">Patients treated for differentiated thyroid cancer should be followed carefully
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with physical examinations, serum quantitative thyroglobulin levels, and radiologic studies based
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on individual risk for recurrent disease.[<a class="bk_pop" href="#CDR0000062913_rl_146_1">1</a>] Approximately 10% to 30% of
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patients thought to be disease free after initial treatment will develop
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recurrence and/or metastases. Of these patients, approximately 80% develop recurrence
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with disease in the neck alone, and 20% develop recurrence with distant metastases. The most
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common site of distant metastasis is the lung. In a single series of 289
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patients who developed recurrences after initial surgery, 16% died of cancer at
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a median time of 5 years following recurrence.[<a class="bk_pop" href="#CDR0000062913_rl_146_2">2</a>] </p><p id="CDR0000062913__237">The prognosis for patients
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with clinically detectable recurrences is generally poor, regardless of cell
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type.[<a class="bk_pop" href="#CDR0000062913_rl_146_3">3</a>] Those patients who recur with local or regional tumor
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detected only by I<sup>131</sup> scan, however, have a better prognosis.[<a class="bk_pop" href="#CDR0000062913_rl_146_4">4</a>] The selection of
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further treatment depends on many factors, including cell type, uptake of
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I<sup>131</sup>, prior treatment, site of recurrence, and individual patient
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considerations. Surgery with or without I<sup>131</sup> ablation can be useful in
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controlling local recurrences, regional node metastases, or, occasionally,
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metastases at other localized sites.[<a class="bk_pop" href="#CDR0000062913_rl_146_5">5</a>] Approximately 50% of the patients
|
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operated on for recurrent tumors can be rendered free of disease with a second
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operation.[<a class="bk_pop" href="#CDR0000062913_rl_146_3">3</a>] Local and regional recurrences detected by I<sup>131</sup> scan and not
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clinically apparent can be treated with I<sup>131</sup> ablation and have an excellent
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prognosis.[<a class="bk_pop" href="#CDR0000062913_rl_146_6">6</a>]
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</p><p id="CDR0000062913__148">Up to 25% of recurrences and metastases from well-differentiated thyroid cancer
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may not show I<sup>131</sup> uptake. For these patients, other imaging techniques shown
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to be of value include imaging with thallium-201, magnetic resonance imaging,
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and pentavalent dimercaptosuccinic acid.[<a class="bk_pop" href="#CDR0000062913_rl_146_7">7</a>] When recurrent disease does not
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concentrate I<sup>131</sup>, or disease recurs after I<sup>131</sup> ablation, sorafenib has been approved by the U.S. Food and Drug Administration as a treatment option. </p><p id="CDR0000062913__280">A phase III randomized, double-blind, placebo-controlled study (<a href="http://cancer.gov/clinicaltrials/search/view?version=healthprofessional&cdrid=656501" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">DECISION</a> [<a href="https://clinicaltrials.gov/show/NCT00984282" title="Study NCT00984282" ref="pagearea=body&targetsite=external&targetcat=link&targettype=clinical-trial">NCT00984282</a>]) evaluated the activity of sorafenib, an orally active, multityrosine kinase inhibitor in patients with progressive iodine-refractory differentiated thyroid cancer.[<a class="bk_pop" href="#CDR0000062913_rl_146_8">8</a>] In the trial, 417 patients with locally advanced or metastatic radioactive iodine-refractory thyroid cancer (papillary, follicular [including Hürthle cell], and poorly differentiated varieties) who had progressed within the past 14 months were randomly assigned to sorafenib (400 mg twice daily) versus placebo. Prior chemotherapy, thalidomide, or targeted therapy were excluded.[<a class="bk_pop" href="#CDR0000062913_rl_146_8">8</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335124/" class="def">Level of evidence: 1iDiii</a></p><ul id="CDR0000062913__391"><li class="half_rhythm"><div> The median progression-free survival in the sorafenib versus placebo groups was 10.8 versus 5.8 months (hazard ratio (HR), 0.59; 95% confidence interval (CI), 0.45–0.76; <i>P</i> < .001). </div></li><li class="half_rhythm"><div> Overall survival (OS) was not significantly improved (HR, 0.80; 95% CI, 0.54–1.19; <i>P</i> = .14, one-sided <i>P</i>-value), but the median OS had not been reached at the time of primary analysis data cutoff and crossover was allowed. </div></li><li class="half_rhythm"><div> Objective response rates (all partial) were 12.2% in the sorafenib group compared with 0.5% in the placebo group. Median time-to-progression was 11.1 months in the sorafenib group compared with 5.7 months in the placebo group (HR, 0.56; 95% CI, 0.43–0.72; <i>P </i>< .001). </div></li><li class="half_rhythm"><div> Adverse events (AEs) occurred in 98.6% of patients treated with sorafenib and 87.6% of patients treated with placebo. The most frequent AEs in the sorafenib group were hand-foot skin reactions (76.3%), diarrhea (68.6%), alopecia (67.1%), and rash or desquamation (50.2%). Most events were grade 1 or 2 in severity. Seven squamous cell carcinomas of the skin occurred in the sorafenib group.</div></li></ul><p id="CDR0000062913__394">External-beam or intraoperative radiation therapy can be
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useful in controlling symptoms related to local tumor recurrences.[<a class="bk_pop" href="#CDR0000062913_rl_146_9">9</a>] Systemic
|
|
chemotherapy can be considered. Chemotherapy has been reported to produce
|
|
occasional objective responses, usually of short duration.[<a class="bk_pop" href="#CDR0000062913_rl_146_4">4</a>,<a class="bk_pop" href="#CDR0000062913_rl_146_10">10</a>]</p><p id="CDR0000062913__395">Patients unresponsive to I<sup>131</sup> should also be considered candidates for clinical trials testing new approaches to this disease.</p><p id="CDR0000062913__396"><b>Treatment options under clinical evaluation: </b></p><p id="CDR0000062913__397">Clinical trials evaluating new treatment approaches to this disease should also
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be considered for these patients. Oral inhibitors of vascular endothelial growth-factor receptors are under clinical evaluation.[<a class="bk_pop" href="#CDR0000062913_rl_146_11">11</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335136/" class="def">Level of evidence: 2Dii</a>] </p><div id="CDR0000062913__TrialSearch_146_sid_9"><h3>Current Clinical Trials</h3><p id="CDR0000062913__TrialSearch_146_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=38810&tt=1&format=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">recurrent thyroid cancer</a>. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.</p><p id="CDR0000062913__TrialSearch_146_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="CDR0000062913_rl_146"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062913_rl_146_1">Ross DS: Long-term management of differentiated thyroid cancer. Endocrinol Metab Clin North Am 19 (3): 719-39, 1990. [<a href="https://pubmed.ncbi.nlm.nih.gov/2261913" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2261913</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_146_2">Mazzaferri EL, Jhiang SM: Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med 97 (5): 418-28, 1994. [<a href="https://pubmed.ncbi.nlm.nih.gov/7977430" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7977430</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_146_3">Goretzki PE, Simon D, Frilling A, et al.: Surgical reintervention for differentiated thyroid cancer. Br J Surg 80 (8): 1009-12, 1993. [<a href="https://pubmed.ncbi.nlm.nih.gov/8402050" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8402050</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_146_4">De Besi P, Busnardo B, Toso S, et al.: Combined chemotherapy with bleomycin, adriamycin, and platinum in advanced thyroid cancer. J Endocrinol Invest 14 (6): 475-80, 1991. [<a href="https://pubmed.ncbi.nlm.nih.gov/1723086" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1723086</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_146_5">Pak H, Gourgiotis L, Chang WI, et al.: Role of metastasectomy in the management of thyroid carcinoma: the NIH experience. J Surg Oncol 82 (1): 10-8, 2003. [<a href="https://pubmed.ncbi.nlm.nih.gov/12501164" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12501164</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_146_6">Coburn M, Teates D, Wanebo HJ: Recurrent thyroid cancer. Role of surgery versus radioactive iodine (I131) Ann Surg 219 (6): 587-93; discussion 593-5, 1994. [<a href="/pmc/articles/PMC1243200/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1243200</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/8203968" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8203968</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_146_7">Mallin WH, Elgazzar AH, Maxon HR 3rd: Imaging modalities in the follow-up of non-iodine avid thyroid carcinoma. Am J Otolaryngol 15 (6): 417-22, 1994 Nov-Dec. [<a href="https://pubmed.ncbi.nlm.nih.gov/7872477" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7872477</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_146_8">Brose MS, Nutting CM, Jarzab B, et al.: Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet 384 (9940): 319-28, 2014. [<a href="/pmc/articles/PMC4366116/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4366116</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24768112" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24768112</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_146_9">Vikram B, Strong EW, Shah JP, et al.: Intraoperative radiotherapy in patients with recurrent head and neck cancer. Am J Surg 150 (4): 485-7, 1985. [<a href="https://pubmed.ncbi.nlm.nih.gov/4051112" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 4051112</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_146_10">Shimaoka K, Schoenfeld DA, DeWys WD, et al.: A randomized trial of doxorubicin versus doxorubicin plus cisplatin in patients with advanced thyroid carcinoma. Cancer 56 (9): 2155-60, 1985. [<a href="https://pubmed.ncbi.nlm.nih.gov/3902203" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3902203</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062913_rl_146_11">Sherman SI, Wirth LJ, Droz JP, et al.: Motesanib diphosphate in progressive differentiated thyroid cancer. N Engl J Med 359 (1): 31-42, 2008. [<a href="https://pubmed.ncbi.nlm.nih.gov/18596272" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18596272</span></a>]</div></li></ol></div></div><div id="CDR0000062913__203"><h2 id="_CDR0000062913__203_">Changes to This Summary (02/04/2016)</h2><p id="CDR0000062913__204">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="CDR0000062913__421"><b><a href="#CDR0000062913__1">General Information About Thyroid Cancer</a></b></p><p id="CDR0000062913__422">Updated <a href="#CDR0000062913__243">statistics</a> with estimated new cases and deaths for 2016 (cited American Cancer Society as reference 1).</p><p id="CDR0000062913__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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editorially independent of NCI. The summary reflects an independent review of
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the literature and does not represent a policy statement of NCI or NIH. More
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information about summary policies and the role of the PDQ Editorial Boards in
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maintaining the PDQ summaries can be found on the <a href="#CDR0000062913__AboutThis_1">About This PDQ Summary</a> and <a href="http://www.cancer.gov/publications/pdq" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ® - NCI's Comprehensive Cancer Database</a> pages.
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</p></div><div id="CDR0000062913__AboutThis_1"><h2 id="_CDR0000062913__AboutThis_1_">About This PDQ Summary</h2><div id="CDR0000062913__AboutThis_2"><h3>Purpose of This Summary</h3><p id="CDR0000062913__AboutThis_3">This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of thyroid 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="CDR0000062913__AboutThis_4"><h3>Reviewers and Updates</h3><p id="CDR0000062913__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="CDR0000062913__AboutThis_22"> Board members review recently published articles each month to determine whether an article should:</p><ul id="CDR0000062913__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="CDR0000062913__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 reviewers for Thyroid Cancer Treatment are:</p><ul><li class="half_rhythm"><div>Scharukh Jalisi, MD, FACS (Boston University Medical Center)</div></li><li class="half_rhythm"><div>Minh Tam Truong, MD (Boston University Medical Center)</div></li></ul><p id="CDR0000062913__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="CDR0000062913__AboutThis_10"><h3>Levels of Evidence</h3><p id="CDR0000062913__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="CDR0000062913__AboutThis_12"><h3>Permission to Use This Summary</h3><p id="CDR0000062913__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="CDR0000062913__AboutThis_14">The preferred citation for this PDQ summary is:</p><p id="CDR0000062913__AboutThis_15">PDQ® Adult Treatment Editorial Board. PDQ Thyroid Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: <a href="http://www.cancer.gov/types/thyroid/hp/thyroid-treatment-pdq" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">http://www.cancer.gov/types/thyroid/hp/thyroid-treatment-pdq</a>. Accessed <MM/DD/YYYY>. [PMID: 26389164]</p><p id="CDR0000062913__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="CDR0000062913__AboutThis_17"><h3>Disclaimer</h3><p id="CDR0000062913__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="CDR0000062913__AboutThis_20"><h3>Contact Us</h3><p id="CDR0000062913__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></div>
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<div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Views</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PDF_download" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK65719.3/?report=reader">PubReader</a></li><li><a href="/books/NBK65719.3/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK65719" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK65719" style="display:none" title="Cite this Page"><div class="bk_tt">PDQ Adult Treatment Editorial Board. Thyroid Cancer Treatment (PDQ®): Health Professional Version. 2016 Feb 4. In: PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002-. <span class="bk_cite_avail"></span></div></div></li><li><a href="#" class="toggle-glossary-link" title="Enable/disable links to the glossary">Disable Glossary Links</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Version History</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter shutter_closed" title="Show/hide content" remembercollapsed="true" pgsec_name="version_history" id="Shutter"></a></div><div class="portlet_content" style="display: none;"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><span class="bk_col_itm"><a href="/books/NBK65719.27/">NBK65719.27</a></span> April 11, 2024</li><li><span class="bk_col_itm"><a href="/books/NBK65719.26/">NBK65719.26</a></span> February 16, 2024</li><li><span class="bk_col_itm"><a 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April 12, 2017</li><li><span class="bk_col_itm"><a href="/books/NBK65719.5/">NBK65719.5</a></span> December 15, 2016</li><li><span class="bk_col_itm"><a href="/books/NBK65719.4/">NBK65719.4</a></span> August 24, 2016</li><li><span class="bk_col_itm">NBK65719.3</span> February 4, 2016 (Displayed Version)</li><li><span class="bk_col_itm"><a href="/books/NBK65719.2/">NBK65719.2</a></span> September 25, 2015</li><li><span class="bk_col_itm"><a href="/books/NBK65719.1/">NBK65719.1</a></span> May 13, 2015</li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>In this Page</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="page-toc" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="#CDR0000062913__1" ref="log$=inpage&link_id=inpage">General Information About Thyroid Cancer</a></li><li><a href="#CDR0000062913__6" ref="log$=inpage&link_id=inpage">Cellular Classification of Thyroid Cancer</a></li><li><a href="#CDR0000062913__14" ref="log$=inpage&link_id=inpage">Stage Information for Thyroid Cancer</a></li><li><a href="#CDR0000062913__75" ref="log$=inpage&link_id=inpage">Stage I and II Papillary and Follicular Thyroid Cancer</a></li><li><a href="#CDR0000062913__103" ref="log$=inpage&link_id=inpage">Stage III Papillary and Follicular Thyroid Cancer</a></li><li><a href="#CDR0000062913__113" ref="log$=inpage&link_id=inpage">Stage IV Papillary and Follicular Thyroid Cancer</a></li><li><a href="#CDR0000062913__132" ref="log$=inpage&link_id=inpage">Medullary Thyroid Cancer</a></li><li><a href="#CDR0000062913__139" ref="log$=inpage&link_id=inpage">Anaplastic Thyroid Cancer</a></li><li><a href="#CDR0000062913__146" ref="log$=inpage&link_id=inpage">Recurrent Thyroid Cancer</a></li><li><a href="#CDR0000062913__203" ref="log$=inpage&link_id=inpage">Changes to This Summary (02/04/2016)</a></li><li><a href="#CDR0000062913__AboutThis_1" ref="log$=inpage&link_id=inpage">About This PDQ Summary</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Related publications</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="document-links" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK65857/">Patient Version</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Related information</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" 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2002</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/26389244" ref="ordinalpos=1&linkpos=2&log$=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> 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 class="brieflinkpopperctrl" href="/pubmed/26389442" ref="ordinalpos=1&linkpos=3&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Retinoblastoma Treatment (PDQ®): Health Professional Version.</a><span class="source">[PDQ Cancer Information Summari...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Retinoblastoma Treatment (PDQ®): Health Professional Version.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">PDQ Pediatric Treatment Editorial Board. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">PDQ Cancer Information Summaries. 2002</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/26389190" ref="ordinalpos=1&linkpos=4&log$=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><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/26389493" ref="ordinalpos=1&linkpos=5&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Cervical Cancer Treatment (PDQ®): Health Professional Version.</a><span class="source">[PDQ Cancer Information Summari...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Cervical Cancer Treatment (PDQ®): Health Professional Version.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">PDQ Adult Treatment Editorial Board. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">PDQ Cancer Information Summaries. 2002</em></div></div></li></ul><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed_reviews&uid=26389164" ref="ordinalpos=1&log$=relatedreviews_seeall&logdbfrom=pubmed">See reviews...</a><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed&uid=26389164" 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" 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