How Effective is the Use of Molecular Testing in Preoperative Decision Making for Management of Indeterminate Thyroid Nodules?

Abstract

Introduction We performed Thyroseq v2 molecular testing on indeterminate thyroid nodules and evaluated whether they underwent a management change from the standard of thyroid lobectomy. Methods We conducted a retrospective analysis of all indeterminate thyroid nodules that underwent Thyroseq v2 molecular testing from 2014 to 2019 at a large academic center. Pathology was reviewed by thyroid cytopathologists. Thyroseq results were reported benign (malignancy probability less than 10%) or suspicious (malignancy probability greater than 30%). The primary endpoint was a management change from a diagnostic lobectomy. Results A total of 142 nodules were included: 113 (80%) Bethesda III and 29 (20%) Bethesda IV. Seventy‐three nodules underwent surgical management and 69 did not. We noted a change in management in 64% (91/142) of nodules. Patients who underwent a change in management to no surgery had a significantly higher rate of benign Thyroseq result than those without a change (75.8% vs. 49.0%, p = 0.001). On logistic regression analysis, a benign Thyroseq result was a positive independent predictor of a change to no surgery (OR 3.87, 95% CI 1.69–8.89). Nodule size, multiple nodules, compressive symptoms, and history of hypothyroidism were not significant. Of the 91 patients who underwent a management change, 71% (65/91) did not undergo surgery. On follow‐up (average 985 ± 615 days), 12% (8/65) of those nodules were growing or developed suspicious features requiring surgery. Conclusions Molecular testing helped avoid surgery in almost half our population with indeterminate thyroid nodules, and benign results may help avoid surgery in asymptomatic patients with indeterminate thyroid nodules.

The Role of “Critical” Ultrasound Reassessment in the Decision-Making of Bethesda III Thyroid Nodules

“…Especially in the last two decades, cytology has been enriched with molecular biology tests, which have improved its initial diagnostic performance [ 19 , 25 , 26 ].…”

Discriminating Interpatient Variabilities of RAS Gene Variants for Precision Detection of Thyroid Cancer

“…Approximately 19% of patients with cancer harbor activating variations from 3 RAS gene isoforms: NRAS (OMIM 164790) in 17% of patients, HRAS (OMIM 190020) in 7% of patients, or KRAS (OMIM 190070) in 75% of patients . Similarly, RAS variants are the second most common alterations in thyroid nodules, with NRAS variants being the dominant isoform followed by HRAS and KRAS . In thyroid tumors, RAS gene variations are detected in tumors spanning a wide spectrum of histological diagnoses, with a prevalence of 10% to 30% in PTC, 40% to 50% in follicular thyroid carcinomas (FTCs), 12% to 85% in follicular adenoma or hyperplasia, and 5% to 46% in noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTPs) .…”

“… 6 Similarly, RAS variants are the second most common alterations in thyroid nodules, with NRAS variants being the dominant isoform followed by HRAS and KRAS . 7 , 8 , 9 , 10 In thyroid tumors, RAS gene variations are detected in tumors spanning a wide spectrum of histological diagnoses, with a prevalence of 10% to 30% in PTC, 11 , 12 , 13 40% to 50% in follicular thyroid carcinomas (FTCs), 14 , 15 12% to 85% in follicular adenoma or hyperplasia, and 5% to 46% in noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTPs). 14 , 16 Indeterminate thyroid nodules carrying RAS variants have shown malignancy rates varying from 9% to 83%, 7 , 8 , 9 , 10 , 17 and such discrepancies can be primarily attributed to the use of small patient cohorts in these studies.…”

“… 7 , 8 , 9 , 10 In thyroid tumors, RAS gene variations are detected in tumors spanning a wide spectrum of histological diagnoses, with a prevalence of 10% to 30% in PTC, 11 , 12 , 13 40% to 50% in follicular thyroid carcinomas (FTCs), 14 , 15 12% to 85% in follicular adenoma or hyperplasia, and 5% to 46% in noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTPs). 14 , 16 Indeterminate thyroid nodules carrying RAS variants have shown malignancy rates varying from 9% to 83%, 7 , 8 , 9 , 10 , 17 and such discrepancies can be primarily attributed to the use of small patient cohorts in these studies. Despite the widespread application of RAS variants in panel tests, assays of RAS variants often yield inconclusive results in detecting malignancy of thyroid nodules, frequently leading to a diagnostic surgery.…”

Letter to Editor: How Effective is the Use of Molecular Testing in Preoperative Decision Making for Management of Indeterminant Thyroid Nodules?

“…We discussed the article “How effective is the use of Molecular testing in preoperative decision making for management of Indeterminant Thyroid Nodules?” by Steinmetz et al in our departmental journal club [1]. We congratulate the authors on their study how molecular testing helps in deciding management of indeterminant thyroid nodules.…”