Thyroid Carcinoma – Anaplastic Carcinoma
Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate
All recommendations are category 2A unless otherwise noted.
Table of Contents
Overview ... MS-3
Epidemiology ... MS-3 Managing Differentiated Thyroid Carcinoma ... MS-4 Radiation-Induced Thyroid Carcinoma ... MS-4 Literature Search Criteria and Guidelines Update Methodology ... 5 Differentiated Thyroid Carcinoma ... MS-5 Clinical Presentation and Diagnosis... MS-5 Initial Workup ... MS-5
FNA Results ... MS-8 Recurrence of Differentiated Thyroid Carcinoma ... MS-10 Prognosis ... MS-10
Age, Stage, and Sex at Diagnosis ... MS-10 Familial Syndromes ... MS-11 Tumor Variables Affecting Prognosis ... MS-11 Histology ... MS-11 Primary Tumor Size ... MS-12 Local Tumor Invasion ... MS-13 Lymph Node Metastases ... MS-13 Distant Metastases ... MS-13
Tumor Staging ... MS-14 Prognostic Scoring Strategies ... MS-14 Surgical Management of Differentiated Thyroid Carcinoma ... MS-15
Ipsilateral Lobectomy Versus Total Thyroidectomy ... MS-15 Completion Thyroidectomy ... MS-16
Surgical Complications ... MS-16
Radioactive Iodine ... MS-16
Postoperative Radioiodine ... MS-16 Diagnostic Total Body Imaging and Thyroid Stunning ... MS-18 Postoperative Administration of Radioiodine ... MS-18 Post-Treatment 131I Imaging ... MS-19 This discussion is being updated to correspond with the
newly updated algorithm. Last updated 07/28/15
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Thyroid Carcinoma
Assessment and Management After Initial Treatment ... MS-19
Recombinant Human TSH ... MS-20 Measuring Serum Tg and Anti-Tg Antibodies ... MS-20 Treating Patients With Positive Tg and Negative Imaging ... MS-21 Thyroid Hormone Suppression of TSH ... MS-21 Adjuvant External-Beam RT ... MS-22 External-Beam RT and Surgical Excision of Metastases ... MS-22 Systemic Therapy ... MS-23
Papillary Thyroid Carcinoma ... MS-23
Surgical Therapy ... MS-23 Radioactive Iodine... MS-25 Systemic Therapy ... MS-26 Adjuvant External-Beam RT ... MS-27 Surveillance and Maintenance ... MS-27 Recurrent and Metastatic Disease ... MS-27 Follicular Thyroid Carcinoma ... MS-29 Hürthle Cell Carcinoma ... MS-30 Medullary Thyroid Carcinoma ... MS-31
Nodule Evaluation and Diagnosis ... MS-31
Sporadic MTC ... MS-31 Inherited MTC ... MS-32
Staging ... MS-33 Surgical Management ... MS-33 Adjuvant RT ... MS-35 Persistently Increased Calcitonin ... MS-35 Postoperative Management and Surveillance ... MS-36 Recurrent or Persistent Disease ... MS-36 Anaplastic Thyroid Carcinoma ... MS-38
Diagnosis ... MS-38 Prognosis ... MS-39 Treatment ... MS-39
Surgery ... MS-39 Radiation Therapy ... MS-39 Systemic Therapy ... MS-40
References ... MS-42
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Thyroid Carcinoma
Overview
Epidemiology
Thyroid nodules are approximately 4 times more common in women than in men. Palpable nodules increase in frequency throughout life, reaching a prevalence of about 5% in the U.S. population for individuals ages 50 years and older.1-3 Nodules are even more prevalent when the thyroid gland is examined at autopsy or surgery, or when using
ultrasonography; 50% of the thyroids studied have nodules, which are almost always benign.2,4 New nodules develop at a rate of about 0.1%
per year, beginning in early life, but they develop at a much higher rate (approximately 2% per year) after exposure to head and neck
irradiation.5,6
By contrast, thyroid carcinoma is uncommon. For the U.S. population, the lifetime risk of being diagnosed with thyroid carcinoma is 1.1%.7 It is estimated that approximately 62,450 new cases of thyroid carcinoma will be diagnosed in the United States in 2015.8 As with thyroid nodules, thyroid carcinoma occurs 2 to 3 times more often in women than in men. Thyroid carcinoma is currently the fourth most common
malignancy diagnosed in women.8 Among persons aged 20 to 34 years, thyroid carcinoma accounts for 15% of all diagnosed malignancies.7 The disease is also diagnosed more often in white North Americans than in African Americans. Although thyroid carcinoma can occur at any age, the peak incidence is approximately age 50 years.7
The main histologic types of thyroid carcinoma are: 1) differentiated (including papillary, follicular, and Hürthle cell); 2) medullary; and 3) anaplastic, which is an aggressive undifferentiated tumor. An average of 58,629 patients per year were diagnosed with thyroid carcinoma from 2008 to 2012.7 Of these 58,629 patients, 89% had papillary carcinoma, 5.1% had follicular carcinoma, 2.2% had Hürthle cell carcinoma, 1.7%
had medullary carcinoma, and 0.8% had anaplastic carcinoma.7 The 5-year relative survival rates for patients with papillary and follicular carcinomas (stages I–III) were 98% and 90%, respectively.9,10
In 2015, it is estimated that approximately 1950 cancer deaths will occur among persons with thyroid carcinoma in the United States.8 Anaplastic carcinoma is almost uniformly lethal; however, most thyroid carcinoma deaths are from papillary, follicular, and Hürthle cell carcinomas, which account for nearly 95% of all thyroid carcinoma cases. Thyroid
carcinoma occurs more often in women; however, mortality rates are lower for younger women.11-15 The incidence of thyroid carcinoma increased almost 310% between 1950 and 2004, but mortality rates decreased more than 44%.14 From 1975 to 2004, thyroid cancer rates doubled in the United States.16 From 1975 to 2009, thyroid cancer rates tripled, possibly due to diagnosis of small papillary carcinomas.17
Although the estimated incidence of thyroid carcinoma increased between 2013 and 2014 (60,220 vs. 62,980, respectively), the incidence did not increase between 2014 and 2015 (62,980 vs.
62,450).8,18 Because overall mortality has not dramatically increased since 1975 (1150 vs. 1950 deaths), the increasing incidence may reflect, at least in part, earlier detection of subclinical disease (ie, small papillary carcinomas).16,17,19-22 However, recent data show the incidence has increased by varying degrees across all tumor sizes and age groups.23-32 The stable age- and gender-adjusted mortality rate for thyroid carcinoma contrasts distinctly with the declining rates for other solid tumors in adults.33,34
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Thyroid Carcinoma address management for the different types of thyroid carcinoma including papillary, follicular, Hürthle cell, medullary, and anaplastic carcinoma. Additional sections in these NCCN Guidelines® include Nodule Evaluation, Principles of
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Thyroid Carcinoma
Stimulating Hormone (TSH) Suppression, Principles of Kinase Inhibitor Therapy in Advanced Thyroid Carcinoma, and the AJCC staging tables.
The Summary of the Guidelines Updates briefly describes the most recent revisions to the algorithms, which have been incorporated into this updated Discussion text (see the NCCN Guidelines for Thyroid Carcinoma).9 For the 2015 update, some of the major revisions include:
1) recommendations for treatment of metastatic disease in patients with differentiated thyroid cancer were extensively revised; 2) lenvatinib is now recommended for progressive and/or symptomatic differentiated disease; and 3) the systemic therapy recommendations for anaplastic carcinoma were revised. This Discussion text describes the
recommendations in the algorithms in greater detail, for example, by including the clinical trial data and other references that support the NCCN Panel’s recommendations in the algorithms. These NCCN Guidelines for Thyroid Carcinoma are updated at least once a year and are available at NCCN.org. By definition, the NCCN Guidelines cannot incorporate all possible clinical variations and are not intended to replace good clinical judgment or individualization of treatments.
Exceptions to the rule were discussed among the NCCN Panel during the process of developing these guidelines.
Managing Differentiated Thyroid Carcinoma
Managing differentiated (ie, papillary, follicular, Hürthle cell) thyroid carcinoma can be a challenge, because very few prospective randomized trials of treatment have been done.35,36 Results from
ongoing randomized trials will not be available for many years, given the typically prolonged course and relative infrequency of these tumors.
Most of the information about treatment comes from studies of large cohorts of patients for whom therapy has not been randomly assigned.
This accounts for much of the disagreement about managing
differentiated carcinoma. Nonetheless, most patients can be cured of
this disease when properly treated by experienced physicians and surgeons.37 The treatment of choice is surgery, followed by radioiodine (131I) in selected patients and thyroxine therapy in most patients.
Radiation-Induced Thyroid Carcinoma
Exposure to ionizing radiation is the only known environmental cause of thyroid carcinoma and usually causes papillary carcinoma.38 The thyroid glands of children are especially vulnerable to ionizing radiation. A child’s thyroid gland has one of the highest risks of developing cancer of any organ. The thyroid gland is the only organ linked to risk at about 0.10 Gy.5 The risk for radiation-induced thyroid carcinoma is greater in females, certain Jewish populations, and patients with a family history of thyroid carcinoma.39 These data suggest that genetic factors are also important in the development of thyroid carcinoma. Beginning within 5 years of irradiation during childhood, new nodules develop at a rate of about 2% annually, reaching a peak incidence within 30 years of irradiation but remaining high at 40 years.5,6
Adults have a very small risk of developing thyroid carcinoma after exposure to 131I.40 After the Chernobyl nuclear reactor accident in 1986, many children and adolescents developed papillary carcinomas after being exposed to 131I fallout.41 It became evident that 131I and other short-lived 131Is were potent thyroid carcinogens in these children, particularly those younger than 10 years of age when they were exposed.42 Iodine deficiency increases the risk for
radiation-induced thyroid cancer.43 Although radiation-induced papillary carcinoma tends to appear more aggressive histologically and to have high recurrence rates, the prognosis for survival is similar to that of spontaneously occurring tumors.44-46 Iodine deficiency is associated with follicular carcinoma and anaplastic carcinomas.
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Thyroid Carcinoma
Literature Search Criteria and Guidelines Update Methodology Prior to the update of this version of the NCCN Guidelines for Thyroid Carcinoma, an electronic search of the PubMed database was
performed to obtain key literature in thyroid carcinoma published between October 1, 2013 and October 1, 2014 using the following search term: thyroid carcinoma. The PubMed database was chosen because it remains the most widely used resource for medical literature and indexes only peer-reviewed biomedical literature. The search results were narrowed by selecting studies in humans published in English. Results were confined to the following article types: Clinical Trial, Phase III; Guideline; Randomized Controlled Trial; Meta-Analysis;
Systematic Reviews; and Validation Studies.
The PubMed search resulted in 126 citations and their potential
relevance was examined. The data from key PubMed articles as well as articles from additional sources deemed as relevant to these Guidelines and discussed by the panel have been included in this version of the Discussion section (eg, e-publications ahead of print, meeting
abstracts). Recommendations for which high-level evidence is lacking are based on the panel’s review of lower-level evidence and expert opinion. The complete details of the Development and Update of the NCCN Guidelines are available on the NCCN webpage.