Final Research Plan

Thyroid Cancer: Screening

April 23, 2015

Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.

The final Research Plan is used to guide a systematic review of the evidence by researchers at an Evidence-based Practice Center. The resulting Evidence Review will form the basis of the USPSTF Recommendation Statement on this topic.

The draft Research Plan was available for comment from January 8 until February 4, 2015 at 5:00 p.m., ET.

Text Description.

The figure is an analytic framework that depicts the five key questions described in the research plan. In general, it illustrates the overarching questions of whether screening asymptomatic adults for thyroid cancer leads to improved health outcomes or potential harms. It also illustrates the intermediate steps and key questions about the accuracy of screening tests for early detection of thyroid cancer. Finally, it illustrates whether treatment of thyroid cancer leads to improved health outcomes or potential harms.

  1. Does screening for thyroid cancer (by palpation or ultrasound) in average-risk adults reduce risk for thyroid-specific mortality or morbidity or all-cause mortality and/or improve quality of life compared with no screening?
    1. Does selective screening of high-risk persons based on a combination of one or more risk factors (e.g., family history or radiation exposure) reduce risk for thyroid-specific mortality or morbidity or all-cause mortality and/or improve quality of life compared with no screening?
  2. What are the test performance characteristics of screening tests (palpation or ultrasound) for detecting malignant thyroid nodules in adults?
  3. What are the harms of screening for thyroid cancer (either as a single application or in a screening program) in adults, including followup confirmatory testing?
  4. Does treatment of screen-detected thyroid cancer reduce thyroid-specific mortality or morbidity or all-cause mortality and/or improve quality of life?
  5. What are the harms of treatment of screen-detected thyroid cancer?

Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.

  1. What is the natural history of thyroid nodules by age, sex, and race/ethnicity?
  2. What is the natural history and prognosis for each type and stage of thyroid cancer (papillary, follicular medullary, and anaplastic)?
  3. What are the test performance characteristics of fine needle aspiration for diagnosing thyroid cancer?
  4. What factors may be associated with the apparent increase in thyroid cancer incidence observed in the United States over the past 30 years?

The Research Approach identifies the study characteristics and criteria that the Evidence-based Practice Center will use to search for publications and to determine whether identified studies should be included or excluded from the Evidence Review. Criteria are overarching as well as specific to each of the key questions (KQs).

  Include Exclude
  • Asymptomatic adults age ≥18 years
  • High-risk populations (persons with a history of radiation exposure or family history of thyroid cancer)
  • Persons who are already under surveillance for thyroid cancer because of previous thyroid cancer
  • Persons who have symptoms that may lead to thyroid evaluation
  • Persons with known inherited genetic syndromes, such as multiple endocrine neoplasia type II, as selection criteria for studies
  • Persons with thyroid disease
  • Children and adolescents
Screening tests KQs 1–3: Palpation or ultrasound of the neck conducted by primary care providers or specialists as part of a routine well-care visit
  • Enhanced ultrasound methods, such as elastography or ultrasound with contrast media
  • Diagnostic procedures (e.g., fine needle aspiration) will be excluded as screening tests but reviewed under harms of screening
  • Other imaging tests (e.g., magnetic resonance imaging, positron emission tomography) that incidentally identify thyroid nodules
  • Blood tests (e.g., calcitonin, thyroid-stimulating hormone)
  • Self-examination
Treatment interventions KQs 4, 5: Surgery, including lobectomy, near-total thyroidectomy, total thyroidectomy, and lymphadenectomy; radioactive iodine ablation
  • Chemotherapy
  • External-beam radiation therapy
  • Nonsurgical ablative treatment, such as thermal ablation, radiofrequency ablation, or ultrasound-guided percutaneous ethanol injection
Comparisons KQs 1–3: No screening

KQs 4, 5: No treatment

Outcomes KQs 1, 4: Reduced morbidity associated with any thyroid cancer (including papillary, follicular, medullary, and anaplastic), including:
  • Improved quality of life
  • Decreased thyroid cancer mortality
  • Decreased all-cause mortality

KQ 2: Sensitivity, specificity, positive predictive value, false-positives, false-negatives, nodule detection rates, and cancer detection rates

KQs 3, 5: Any harm from screening or treatment, including overdiagnosis,* diagnostic tests, overtreatment,** psychosocial harms, secondary malignancies, or procedure-related adverse events
Incidentally-identified thyroid nodules
  • U.S. primary care settings
  • Nations categorized as “High” on the Human Development Index (as defined by the World Health Organization)
Nations with environmental disasters that led to very high radiation exposure (e.g., Ukraine, Japan)
Study designs Fair- to good-quality studies published between January 1, 1966 and March 31, 2015

KQ 1: Randomized, controlled trials

KQ 2: Diagnostic accuracy studies with a reference standard; systematic evidence reviews

KQs 3, 5: Randomized, controlled trials; controlled clinical trials; cohort studies; case-control studies

KQ 4: Randomized, controlled trials; controlled clinical trials; cohort studies
Poor-quality studies with a fatal flaw; studies outside of the publication window; case reports and case series; decision analyses

*Diagnosis of nonpalpable nodules measuring <1 cm and/or fine needle aspiration of nodules not meeting revised 2009 American Thyroid Association criteria for fine needle aspiration.
**Including treatment of an overdiagnosed nodule and extended followup of benign nodules.

The draft Research Plan was posted for public comment on the USPSTF Web site from January 8 to February 4, 2015. In response, the Task Force clarified that this review will include palpation as a separate but potential screening method and that morbidity is an outcome of interest by adding quality of life to the analytic framework. The exclusion criteria were refined to exclude alcohol ablation, as it is a treatment for benign thyroid nodules, as well as screening in populations with thyroid disease, who are most likely already under surveillance. In addition, Hurthle cell was removed as a type of thyroid cancer, as the World Health Organization defines it  as a variant of follicular carcinoma.