Monday, December 2, 2019

Thyroid Cancer Screening (PDQ®)–Health Professional Version - National Cancer Institute

Thyroid Cancer Screening (PDQ®)–Health Professional Version - National Cancer Institute

National Cancer Institute



Thyroid Cancer Screening (PDQ®)–Health Professional Version

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Overview

Note: A separate PDQ summary on Thyroid Cancer Treatment is also available.

Benefits

Based on solid evidence, screening for thyroid cancer does not result in a decrease in thyroid cancer mortality.
Magnitude of Effect: No evidence of benefit.
  • Study Design: Ecologic studies and analyses of changes in thyroid cancer incidence and mortality after screening adoption.
  • Internal Validity: Good.
  • Consistency: Good.
  • External Validity: Good.

Harms

Based on solid evidence, screening for thyroid cancer results in overdiagnosis and overtreatment. Treatment for thyroid cancer usually results in long-term and clinically relevant sequelae. Other known harms associated with thyroid cancer screening are psychologic consequences of both false-positive tests and unnecessary diagnoses.
Magnitude of Effect: Moderate.
  • Study Design: Ecologic studies, analyses of changes in thyroid cancer incidence and mortality after screening adoption, and observational studies.
  • Internal Validity: Good.
  • Consistency: Good.
  • External Validity: Good.

Description of the Evidence

Incidence and Mortality

In 2019, an estimated 52,070 new cases of thyroid cancer will be diagnosed in the United States, and an estimated 2,170 people will die of the disease.[1] Surveillance, Epidemiology, and End Results (SEER) data suggest that the incidence of thyroid cancer in women is about three times higher than the incidence of thyroid cancer in men (21.0 vs. 7.1 per 100,000 per year), although the mortality rate does not differ by sex (0.5 per 100,000 per year for both).[2] Nearly all cases are diagnosed at either the local stage (68%) or the regional stage (27%).[2] The 10-year relative survival is 97%.[2]
Thyroid cancer represents less than 5% of all cancer diagnoses in the United States and less than 1% of all cancer deaths.[2] Thyroid cancer is most frequently diagnosed in people aged 45 to 54 years,[2] although it is the most frequently diagnosed cancer in women aged 20 to 34 years.[3] In 2014, more than 750,000 people in the United States had been diagnosed with thyroid cancer at some point in their lives.[2]
About 95% of thyroid cancers are well differentiated.[4] Well-differentiated thyroid cancers include papillary thyroid cancers and follicular thyroid cancers, which represent 84% and 11% of all thyroid cancers, respectively.[4] Medullary and anaplastic thyroid cancers account for 2% and 1% of thyroid cancers, respectively.[4] Well-differentiated tumors are highly treatable and usually curable. (Refer to the PDQ summary on Thyroid Cancer Treatment (Adult) for more information.) The 10-year relative survival for papillary and follicular cancers are 99% and 95%, respectively.[2] The 10-year relative survival for medullary thyroid cancer is 82%.[2] Although rare, anaplastic tumors have a poor prognosis, with a 10-year relative survival of 8%, and account for 20% of thyroid cancer deaths.[4]
Incidence rates of thyroid cancer in the United States have been rising for at least 40 years. From 1974 to 2013, the average annual rise in incidence was 3.6% (95% confidence interval [CI], 3.2–3.9), a change driven primarily by an increased incidence of papillary thyroid cancer (average annual percent change, 4.4%; 95% CI, 4.0–4.7).[4] A rise in incidence has also been seen in other countries, including the United Kingdom [5] and Nordic countries.[6] The greatest rise has been seen in South Korea, where the incidence of thyroid cancer in 2011 was 15 times what it was in 1993.[7] The rise in incidence tracks closely with the uptake of thyroid cancer screening in Korea.[7]

Risk Factors

Radiation therapy administered in infancy or childhood for benign conditions of the head and neck (such as enlarged thymus, tonsils, or adenoids; or acne) increases the risk of thyroid cancer, with diagnosis occurring in as few as 5 years after exposure.[8] Radiation exposure as a consequence of nuclear fallout has also been associated with a high risk of thyroid cancer, especially in children.[9-11] Other risk factors include family history of thyroid disease (including thyroid cancer), history of enlarged thyroid (goiter), female sex, and Asian race.[12] A hereditary condition, multiple endocrine neoplasia type 2 (MEN2), increases the risk of medullary thyroid cancer caused by mutations in the RET gene.[1,13] (Refer to the PDQ summary on Genetics of Endocrine and Neuroendocrine Neoplasias for more information.)

Evidence of No Benefit Associated With Screening

Screening for thyroid cancer is primarily accomplished by neck palpation or ultrasound imaging. In the absence of formal screening, asymptomatic thyroid cancers are most commonly detected incidentally on cross-sectional imaging performed for other medical conditions or on surgical specimens of benign diseases such as goiter.[14]
The efficacy of thyroid cancer screening has never been evaluated in a randomized controlled trial (RCT).[15] No RCTs of intermediate endpoints (e.g., changes in stage at diagnosis) have been conducted. No population-based screening programs for thyroid cancer exist in the United States, the United Kingdom, or Europe, although neck palpation screening results in incidental detection of asymptomatic cancers. Over time, U.S. and U.K. thyroid cancer incidence rates have increased, but thyroid cancer mortality has remained constant or decreased slightly.[4,5] That pattern is consistent with the detection of cancers that are not destined to cause symptoms or result in death (overdiagnosis).
In South Korea, thyroid cancer screening increased dramatically in conjunction with the 1999 establishment of a free national cancer screening program. Although not offered as part of the package of free screening exams, thyroid cancer screening with ultrasound was offered simultaneously at low cost in most clinics, and many South Koreans opted for the exams.[16] Thyroid cancer incidence in South Korea increased 15-fold from 1993 to 2011, although no change in thyroid cancer mortality occurred concurrently.[17] In 2011, the number of people diagnosed with thyroid cancer (40,000) was more than 100 times higher than the number who died of thyroid cancer (typically 300–400 each year, with little change in mortality rates since 1999).[17,18] The practice of thyroid cancer screening in South Korea began to wane in 2013 because of concerns about overdiagnosis and overtreatment; in 2015, the Korean Committee for National Cancer Screening Guidelines issued a recommendation against thyroid cancer screening with ultrasonography for healthy individuals.[18]
In 2017, the U.S. Preventive Services Task Force recommended against thyroid cancer screening; the Task Force’s conclusion, based on observational evidence, was that “the net benefit of screening for thyroid cancer is negative.”[15,19] The American College of Radiology does not recommend screening for thyroid cancer with imaging and, in a white paper, addressed the management of incidental nodules detected on imaging for other medical problems.[20] The American College of Radiology stated that workup was not required for incidental thyroid nodules detected on imaging if nodules were smaller than 1 cm in patients younger than 35 years and smaller than 1.5 cm in patients aged 35 years and older.
Much of what is known about the impact of thyroid cancer screening comes from South Korea’s experience. Investigators examined thyroid cancer trends in South Korea using the following three data sources:[16]
  • The 2010 Korea Community Health Survey.
  • The Korea Cancer Registry.
  • Mortality data from Statistics Korea.
The Korea Community Health Survey asked more than 200,000 people whether they had been screened for thyroid cancer in the past 2 years. Thyroid cancer incidence from 2008 to 2010, mortality from 2007 to 2010, and the percent of people who reported thyroid cancer screening were calculated for each of the 16 administrative units of Korea, and correlations were calculated. The authors identified a strong positive correlation between rates of reported thyroid cancer screening and thyroid cancer incidence in the 16 areas (correlation coefficient [r], 0.77; 95% CI, 0.70–0.82), with the correlation stronger in women (r, 0.88; 95% CI, 0.83–0.92) than in men (r, 0.76; 95% CI, 0.67–0.84). However, there was no correlation between thyroid cancer incidence and mortality (r, -0.08; 95% CI, -0.59 to -0.63). Thyroid cancer screening was correlated with increased detection of papillary thyroid cancer (r, 0.74; 95% CI, 0.59–0.88) and no other histologic subtypes.[16]
The South Korean data are limited because they are not experimental; however, they present a compelling argument against thyroid cancer screening in community settings. Similar trends of increased incidence without decreased mortality in other developed nations support the interpretation of the South Korean findings.[21]

Evidence of Harm Associated With Screening

Although neck palpation and thyroid ultrasound carry very low risk, a suspicious screening result can set off a chain of events that may lead to opportunities for harms.[15,19] The next step after detection of a suspicious nodule is diagnostic evaluation with fine-needle aspiration of the lesion. The risks of thyroid fine-needle aspiration are hospitalization, postprocedural hematoma, and needle tract tumor implantation, although two observational studies suggest that the rate of each of the three outcomes is lower than 1%.[15] More importantly, the results of cytology can lead to additional tests and surgery. In a meta-analysis of 23,445 nodules that were biopsied, 60% of the nodules were benign and 5% of the nodules were malignant; however, the remaining 35% of the nodules required repeat biopsy or surgery.[22] In patients who had a diagnostic lobectomy or excision, 64% of the nodules were benign on final histology.[22]
Thyroid surgery for benign disease has the same risks as it does for malignancy. In 2013, about 80% of surgeries for small localized papillary thyroid cancers were total thyroidectomies and 20% were lobectomies; however, the 25-year cumulative risk of death caused by thyroid cancer does not differ by type of surgery.[23] Surgical risks are lower for a lobectomy than for total thyroidectomy. In addition to the general risks of surgery, specific risks of thyroid surgery include recurrent laryngeal nerve injury and hypoparathyroidism. Recurrent laryngeal nerve injury causes vocal cord paresis, which can result in difficulty speaking, difficulty swallowing, and hoarseness. Breathing difficulties are possible if both laryngeal nerves are affected.[24,25] Hypoparathyroidism leads to hypocalcemia. A cross-sectional population-based survey of 2,632 thyroid cancer patients, 2 to 4 years after diagnosis, from two U.S. SEER registries reported that 25.8% of patients had voice changes more than 3 months after surgery and 4.7% of patients had vocal fold paralysis or paresis.[26]
A meta-analysis of hypoparathyroidism lasting more than 6 months after thyroidectomy produced a summary event measure of 3.57 per 100 procedures (95% CI, 2.12–5.93), and summary event measures of 1.86 per 100 procedures (95% CI, 0.84–4.04) and 3.46 per 100 procedures (95% CI, 1.20–9.56) with unilateral and bilateral lymph node dissection, respectively. Event measures from individual studies were quite variable and, in most instances, were based on very small numbers of events; however, summary measures did not vary much by extent of thyroid or lymph node resection.[15]
A meta-analysis of laryngeal nerve palsy (a cause of unilateral vocal cord paralysis and hoarseness) lasting more than 6 months produced a summary event measure of 1.46 per 100 procedures. Although the individual study measures were less variable than those for hypoparathyroidism, the measures were based on very small numbers of events. Patients who have total thyroidectomy also require lifelong thyroid-replacement therapy and corresponding blood level monitoring.[24,25] In patients who undergo total thyroidectomy, the process of optimizing hormone replacement therapy and the resultant changes in other medications, weight, or estrogen status may cause iatrogenic hypothyroidism or hyperthyroidism.
Patients with malignant nodules have additional risks if they receive radioactive iodine therapy. Studies of harms of radioactive iodine treatment addressed the risk of second primary malignancy and permanent harms on the salivary glands. The authors concluded, from the available eight studies, that there is a small increase in primary second malignancies, on the order of 12 to 13 excess cancers per 10,000 patients.[15] The authors expressed some concern with that estimate, though, given differences in study designs, reporting of administered doses, and the fact that changes in indication and dose had occurred over time.[15] The most-common permanent salivary adverse effect was xerostomia (dry mouth) which, in turn, is a risk factor for dental caries; the percentage of affected individuals ranged from 2.3% to 35%.[15] Xerostomia increases the chance of dental decay, demineralization of teeth, tooth sensitivity, and oral infections.[27]
The harms of surgery and radioactive iodine treatments raise concerns because many of these treated cancers may not progress to cause morbidity and mortality. There are no RCTs of thyroid cancer screening that could be used to estimate overdiagnosis, but it is clear from ecologic data that thyroid cancer screening results in detection of thyroid cancers that would not have been diagnosed otherwise.[20] Increases in incidence without changes in mortality in South Korea and other countries in which opportunistic thyroid cancer screening occurs cannot be explained by changes in treatment or risk factor prevalence over the years. Investigators measured thyroid cancer overdiagnosis by studying cancer registry data from high-income countries, estimating age-specific trends in thyroid cancer incidence in the 1960s before ultrasound was introduced, then comparing the shape of the age-specific curves since the 1980s.[20] The investigators reported the rate of overdiagnosis in the United States to be increasing and estimated that it accounted for 77% of thyroid cancer cases. The estimation for overdiagnosis in South Korea was 90% of thyroid cancers cases.
Autopsy studies also lend credence to overdiagnosis resulting from thyroid cancer screening.[15] A 2014 review of 15 autopsy studies reported a 12% yield of papillary thyroid cancers, although the range across studies was wide (1%–36%). Natural history studies have demonstrated the slow-growing nature of thyroid tumors, tumor stability, and low potential for recurrence.[15,28]
References
  1. American Cancer Society: Cancer Facts and Figures 2019. Atlanta, Ga: American Cancer Society, 2019. Available onlineExit Disclaimer. Last accessed June 7, 2019.
  2. Howlader N, Noone AM, Krapcho M, et al., eds.: SEER Cancer Statistics Review (CSR) 1975-2014. Bethesda, Md: National Cancer Institute. Also available online. Last accessed August 2, 2019.
  3. American Cancer Society: Cancer Facts and Figures 2017. Atlanta, Ga: American Cancer Society, 2017. Available onlineExit Disclaimer. Last accessed November 8, 2019.
  4. Lim H, Devesa SS, Sosa JA, et al.: Trends in Thyroid Cancer Incidence and Mortality in the United States, 1974-2013. JAMA 317 (13): 1338-1348, 2017. [PUBMED Abstract]
  5. Cancer Research UK: Thyroid Cancer Incidence Statistics. London, UK: Cancer Research UK. Available onlineExit Disclaimer. Last accessed November 8, 2019.
  6. Carlberg M, Hedendahl L, Ahonen M, et al.: Increasing incidence of thyroid cancer in the Nordic countries with main focus on Swedish data. BMC Cancer 16: 426, 2016. [PUBMED Abstract]
  7. Ahn HS, Welch HG: South Korea's Thyroid-Cancer "Epidemic"--Turning the Tide. N Engl J Med 373 (24): 2389-90, 2015. [PUBMED Abstract]
  8. 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.
  9. 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. [PUBMED Abstract]
  10. 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. [PUBMED Abstract]
  11. 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. [PUBMED Abstract]
  12. 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. [PUBMED Abstract]
  13. Salvatore G, Giannini R, Faviana P, et al.: Analysis of BRAF point mutation and RET/PTC rearrangement refines the fine-needle aspiration diagnosis of papillary thyroid carcinoma. J Clin Endocrinol Metab 89 (10): 5175-80, 2004. [PUBMED Abstract]
  14. Bahl M, Sosa JA, Nelson RC, et al.: Trends in incidentally identified thyroid cancers over a decade: a retrospective analysis of 2,090 surgical patients. World J Surg 38 (6): 1312-7, 2014. [PUBMED Abstract]
  15. Lin JS, Bowles EJA, Williams SB, et al.: Screening for Thyroid Cancer: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA 317 (18): 1888-1903, 2017. [PUBMED Abstract]
  16. Ahn HS, Kim HJ, Kim KH, et al.: Thyroid Cancer Screening in South Korea Increases Detection of Papillary Cancers with No Impact on Other Subtypes or Thyroid Cancer Mortality. Thyroid 26 (11): 1535-1540, 2016. [PUBMED Abstract]
  17. Ahn HS, Kim HJ, Welch HG: Korea's thyroid-cancer "epidemic"--screening and overdiagnosis. N Engl J Med 371 (19): 1765-7, 2014. [PUBMED Abstract]
  18. Park S, Oh CM, Cho H, et al.: Association between screening and the thyroid cancer "epidemic" in South Korea: evidence from a nationwide study. BMJ 355: i5745, 2016. [PUBMED Abstract]
  19. Bibbins-Domingo K, Grossman DC, Curry SJ, et al.: Screening for Thyroid Cancer: US Preventive Services Task Force Recommendation Statement. JAMA 317 (18): 1882-1887, 2017. [PUBMED Abstract]
  20. Hoang JK, Langer JE, Middleton WD, et al.: Managing incidental thyroid nodules detected on imaging: white paper of the ACR Incidental Thyroid Findings Committee. J Am Coll Radiol 12 (2): 143-50, 2015. [PUBMED Abstract]
  21. Vaccarella S, Franceschi S, Bray F, et al.: Worldwide Thyroid-Cancer Epidemic? The Increasing Impact of Overdiagnosis. N Engl J Med 375 (7): 614-7, 2016. [PUBMED Abstract]
  22. Bongiovanni M, Spitale A, Faquin WC, et al.: The Bethesda System for Reporting Thyroid Cytopathology: a meta-analysis. Acta Cytol 56 (4): 333-9, 2012. [PUBMED Abstract]
  23. Welch HG, Doherty GM: Saving Thyroids - Overtreatment of Small Papillary Cancers. N Engl J Med 379 (4): 310-312, 2018. [PUBMED Abstract]
  24. Sandhu GS, Nouraei SAR: Laryngeal and esophageal trauma. In: Flint PW, Haughey BH, Lund V, et al., eds.: Cummings Otolaryngology—Head and Neck Surgery. 6th ed. Philadelphia, PA: Saunders, 2015, pp 970-81.
  25. Smith PW, Hanks JB: Evaluation of the isolated neck mass. In: Cameron JL, Cameron AM, eds.: Current Surgical Therapy. 11th ed. Philadelphia, PA: Saunders, 2014, pp 718-23.
  26. Kovatch KJ, Reyes-Gastelum D, Hughes DT, et al.: Assessment of Voice Outcomes Following Surgery for Thyroid Cancer. JAMA Otolaryngol Head Neck Surg : , 2019. [PUBMED Abstract]
  27. Plemons JM, Al-Hashimi I, Marek CL, et al.: Managing xerostomia and salivary gland hypofunction: executive summary of a report from the American Dental Association Council on Scientific Affairs. J Am Dent Assoc 145 (8): 867-73, 2014. [PUBMED Abstract]
  28. Oda H, Miyauchi A, Ito Y, et al.: Incidences of Unfavorable Events in the Management of Low-Risk Papillary Microcarcinoma of the Thyroid by Active Surveillance Versus Immediate Surgery. Thyroid 26 (1): 150-5, 2016. [PUBMED Abstract]

Changes to This Summary (11/08/2019)

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.
Description of the Evidence
Added text to state that a cross-sectional population-based survey of 2,632 thyroid cancer patients, 2 to 4 years after diagnosis, from two U.S. SEER registries reported that 25.8% of patients had voice changes more than 3 months after surgery and 4.7% of patients had vocal fold paralysis or paresis (cited Kovatch et al. as reference 26).
This summary is written and maintained by the PDQ Screening and Prevention Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about thyroid cancer screening. 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.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Screening and Prevention 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).
Board members review recently published articles each month to determine whether an article should:
  • be discussed at a meeting,
  • be cited with text, or
  • replace or update an existing article that is already cited.
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.
Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

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 Screening and Prevention Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

Permission to Use This Summary

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].”
The preferred citation for this PDQ summary is:
PDQ® Screening and Prevention Editorial Board. PDQ Thyroid Cancer Screening. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/thyroid/hp/thryoid-screening-pdq. Accessed <MM/DD/YYYY>. [PMID: 28876831]
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