ThyroSPEC™

Prospective observational study (Stewardson et al., Thyroid, 2023)

A prospective observational study was conducted in the AHS Calgary Health Care Region, where a guidelines-based thyroid nodule pathway (PCN pathway) including thyroid nodule ultrasound malignancy risk stratification (EFN white paper) and determination of local malignancy risk for each Bethesda category (Ghaznavi et al., Acta Cytologica, 2022) has recently been implemented.

All 615 patients in Southern Alberta with an AUS/FLUS or FN/SFN thyroid nodule diagnosed from July 30, 2020, until July 31, 2022, were included. Electronic health records were used for this study (IRB approval: HREBA.CHC-20-0068) to determine demographics, laboratory results, clinical history, surgical decision making, ultrasound findings, cytology diagnoses, molecular test results, outcomes, surgical procedure, histopathologic findings based on standardized synoptic reporting, and follow-up:

Genomic alterations in the following genes were detected by ThyroSPEC™ in the FNA samples:

ThyroSPEC™ test performance range from resected nodules only, to all resected nodules and unresected nodules with more than 1 year follow-up:

Cytology	ROM	n	Sens	Spec	NPV	PPV
All Indeterminates	21 – 44%	179 – 377	72%	70 – 78%	76 – 91%	46 – 65%
AUS/FLUS	17 – 41%	139 – 327	74%	67 – 78%	79 – 93%	42 – 61%
FN/SFN	42 – 53%	40 – 50	67%	79 – 84%	70 – 77%	70 – 82%
ATA Low Suspicion, TR3	20 – 35%	52 – 88	72%	56 – 83%	79 – 92%	46 – 52%
ATA Intermediate Suspicion, TR4	22 – 49%	71 – 161	80%	69 – 79%	78 – 93%	52 – 72%
ATA High Suspicion, TR5	17 – 41%	32 – 78	46%	83 – 84%	70 – 89%	35 – 67%

Proposed clinical management recommendations for indeterminate nodules in our setting based on average malignancy rates in this study, according to molecular test result and ultrasound malignancy risk:

Category	Average Malignancy Risk	Management Options ATA Benign – Low Risk ACR-TIRADS 1-3	Management Options ATA Intermediate – High Risk ACR-TIRADS 4-5
Failed quality control	n/a	While noting the lower risk in this USMR category, management should also account for cytology diagnosis and clinical assessment	While noting the higher risk in this USMR category, management should also account for cytology diagnosis and clinical assessment
No mutation detected or benign molecular marker	~30%	Ongoing surveillance preferred	Molecular testing has not changed management recommendations based on cytology diagnosis and clinical assessment
Intermediate risk mutation	~60%	Refer to endocrinology to discuss lobectomy or ongoing surveillance depending on clinical assessment and patient preference	Lobectomy preferred
Malignant molecular marker	~90%	Total thyroidectomy, but depending on size and the mutation lobectomy may be considered	Total thyroidectomy, but depending on size and the mutation lobectomy may be considered
High risk mutations	~100%	Total thyroidectomy	Total thyroidectomy