title: The impact of benign gene expression classifier test results on the endocrinologist-patient decision to operate on patients with thyroid nodules with indeterminate fine-needle aspiration cytopathology.
abstract: BACKGROUND
  Seventy-five percent of thyroid nodules with indeterminate fine-needle aspiration (FNA) cytology are found to be benign postoperatively. A novel genomic test, the Afirma gene expression classifier (AGEC), has been available for clinical use in the United States, since late 2010. In 2010, two modest-sized validation studies showed that the AGEC could identify a benign gene expression signature in indeterminate cytology thyroid FNA samples with a negative predictive value >95%. The objective of this study was to evaluate how the AGEC impacted the joint decision of the endocrinologist and patient to operate when FNA cytology was indeterminate, but the AGEC reading of the nodule was benign.
  
  
  METHODS
  In this cross-sectional cohort study, data were contributed retrospectively by 51 endocrinologists at 21 practice sites that had previously obtained ≥3 benign AGEC readings in ≥1 cm nodules with indeterminate FNA cytology readings. Information regarding demographic data, nodule size and location, decision to operate, surgery type (hemithyroidectomy [HT] or total thyroidectomy [TT]), and reason for recommending surgery was retrospectively collected.
  
  
  RESULTS
  Compared to a 74% previous historical rate of surgery for cytologically indeterminate nodules, the operative rate fell to 7.6% during the period that AGEC were obtained in the clinical practices, a highly significant reduction in the decision to operate (p<0.001). The rate of surgery on cytologically indeterminate nodules that were benign by the AGEC reading did not differ from the historically reported rate of operation on cytologically benign nodules (p=0.41). The four primary reasons reported by the physicians for operating on nodules with a benign AGEC reading, in descending order: large nodule size (46.4%), symptomatic nodules (25.0%), rapidly growing nodules (10.7%), or a second suspicious or malignant nodule in the same patient (10.7%). These reasons are concordant with those typically given for operation on cytologically benign nodules.
  
  
  CONCLUSIONS
  In a substantial group of medical practices, obtaining an AGEC test in patients with cytologically indeterminate nodules was associated with a striking reduction in the rate of diagnostic thyroidectomy. Approximately, one surgery was avoided for every two AGEC tests run on thyroid FNAs with indeterminate cytology.
authors.affiliation: Endocrinology Associates, Phoenix, Arizona, USA.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Duick
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Klopper
authors.forename: James C
authors.initials: JC
authors.lastname: Diggans
authors.forename: Lyssa
authors.initials: L
authors.lastname: Friedman
authors.forename: Giulia C
authors.initials: GC
authors.lastname: Kennedy
authors.forename: Richard B
authors.initials: RB
authors.lastname: Lanman
authors.forename: Bryan
authors.initials: B
authors.lastname: McIver
mesh_terms: D044963:Biopsy, Fine-Needle; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D010358:Patient Participation; D012189:Retrospective Studies; D016606:Thyroid Nodule / Q000235:genetics* / Q000473:pathology / Q000601:surgery*