Effect of Gene Expression Classifier Molecular Testing on the Surgical Decision-Making Process for Patients With Thyroid Nodules

JAMA Otolaryngol Head Neck Surg. 2015 Dec;141(12):1082-8. doi: 10.1001/jamaoto.2015.2708.

Abstract

Importance: Commercial molecular testing, such as the gene expression classifier (GEC), is now being used in the work up of cytologically indeterminate thyroid nodules. While this test may be helpful in ruling out malignancy in a thyroid nodule, its effect on surgical decision making has yet to be fully defined.

Objective: We aimed to determine the effect and outcome of GEC test results on the decision-making process for patients with thyroid nodules presenting for surgical consultation.

Design, setting, and participants: A surgical management algorithm was developed that incorporated individual Bethesda System for Reporting Thyroid Cytopathology classifications, in addition to clinical, laboratory, and radiological findings. We then retrospectively applied this algorithm to 273 consecutive patients with thyroid nodules and GEC test results who had presented for surgical consultation between February 1, 2012, and December 31, 2014.

Interventions: GEC testing.

Main outcomes and measures: Changes in management were recorded to identify the effect of GEC testing on the surgical decision-making process. An alteration in management of 20% of cases was considered significant.

Results: Of the 273 consecutive patients assessed by the GEC, mean (SD) age was 50.8 (14.7) years, 204 (74.7%) were female, and the mean (SD) nodule size was 2.4 (1.3) cm. Test results were suspicious for 233 (85.3%); benign for 31 (11.4%); and indeterminate for 8 (2.9%). The GEC test was also positive for medullary thyroid cancer for 1 patient (0.4%). The GEC test was correctly used as a rule-out test in only 127 patients (46.5%) with indeterminate nodules who lacked a clinical indication for surgery. The clinical management plan of only 23 (8.4%) patients was altered as a result of GEC test results, and of these 23 patients who proceeded to surgery, 16 patients (72.7%) were found to be inappropriately overtreated relative to postoperative histopathology analysis. We found that GEC testing did not affect the surgical decision-making process in 250 (91.6%) of our patients. In 146 cases, the use of GEC testing was not clinically indicated, and the test was being overused in patients for whom the results would not change surgical management. The positive predictive value of the GEC test for cytologically indeterminate nodules was 42.1%, and the negative predictive value was 83.3%.

Conclusions and relevance: The GEC testing did not significantly affect the surgical decision-making process. Gene expression classifier testing is often used incorrectly and is overused in patients for whom the results would not change management. The GEC test demonstrated a lower than expected negative predictive value, and there was evidence of overtreatment among patients whose treatment was altered based on this test.

MeSH terms

  • Algorithms
  • Cytodiagnosis
  • Decision Making*
  • Female
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Middle Aged
  • Patient Selection*
  • Thyroid Nodule / genetics*
  • Thyroid Nodule / pathology
  • Thyroid Nodule / surgery*