What is the best test between Afirma, ThyroSeq, and ThyGenX (Thyroid Genomic Expression Test)/ThyraMIR (Thyroid Molecular Index Reporter) for thyroid cancer diagnosis?

Comparison of Molecular Testing Options for Thyroid Cancer Diagnosis

ThyroSeq v3 is the best molecular test for thyroid cancer diagnosis due to its superior performance in both ruling in and ruling out malignancy, particularly with its high sensitivity (92.9%) and specificity (69.3%) for detecting Hürthle cell cancers.1

Overview of Available Tests

• Afirma Genomic Sequencing Classifier (GSC), ThyroSeq v3, and ThyGenX/ThyraMIR are the three main commercially available molecular tests for evaluating indeterminate thyroid nodules 2, 3
• These tests are primarily used to reduce unnecessary diagnostic surgeries for thyroid nodules with indeterminate cytology (Bethesda III and IV categories) 4, 3
• Molecular testing is particularly valuable when fine-needle aspiration cytology (FNAC) results are inconclusive 2

Performance Comparison

ThyroSeq v3

• Analyzes 112 genes for various genetic alterations 1
• Demonstrates superior sensitivity (92.9%) and specificity (69.3%) for detecting Hürthle cell cancers specifically 1
• Has been validated in both tissue samples (238) and FNA samples (174) with known surgical follow-up 1
• Offers both high negative predictive value (NPV) and positive predictive value (PPV), allowing it to function as both a "rule in" and "rule out" test 2

Afirma GSC

• Shows improved performance over the older Afirma Gene Expression Classifier (GEC) 1, 5
• Uses dedicated classifiers to differentiate Hürthle cell specimens from non-Hürthle specimens and neoplastic from nonneoplastic Hürthle specimens 1
• Demonstrates 88.9% sensitivity for detecting Hürthle cell malignancies and 58.8% specificity for identifying benign Hürthle lesions 1
• Has the highest benign call rate (78%) compared to Afirma GEC (60%) and ThyroSeq (66%) in some studies 5
• Shows excellent NPV (96.97%) in recent studies, making it a reliable "rule out" test 4

ThyGenX/ThyraMIR

• Combines DNA mutation analysis and RNA translocation fusion markers 2
• Shows good NPV and PPV in validation studies 2
• In recent studies, demonstrates a PPV of 45.00% and overall accuracy of 81.42% 4

Special Considerations for Hürthle Cell Neoplasms

• Historically, molecular diagnostics have performed poorly for Hürthle cell neoplasms, with high false-positive rates for malignancy 1, 6
• Newer versions of tests have shown improvement, particularly ThyroSeq v3 and Afirma GSC 1
• The NCCN panel acknowledges that while data on newer tests are encouraging, they remain cautious about recommending molecular testing for Hürthle cell lesions 1
• Definitive diagnosis of Hürthle cell carcinoma requires histological evidence of capsular and/or vascular invasion, which can only be determined after surgical excision 6

Impact on Clinical Management

• Molecular testing has significantly reduced unnecessary thyroid surgeries for benign nodules 4, 3
• In one study, only 25% of patients in the Afirma GSC + XA cohort underwent surgery, considerably decreasing unnecessary surgical interventions 4
• Cost remains a limiting factor for widespread adoption, particularly outside the United States 7
• Some tests provide information on underlying molecular drivers of thyroid cancer, which may support decision-making in initial management planning 3

Conclusion

Based on the most recent evidence, ThyroSeq v3 demonstrates the best overall performance for thyroid cancer diagnosis, particularly for Hürthle cell neoplasms, with its high sensitivity (92.9%) and specificity (69.3%). However, all three tests (ThyroSeq v3, Afirma GSC, and ThyGenX/ThyraMIR) have shown value in reducing unnecessary surgeries, with each having particular strengths in different clinical scenarios.