What is the recommended approach for risk stratification of thyroid cancer?

Risk Stratification for Thyroid Cancer

The recommended approach for risk stratification of thyroid cancer should utilize a dual system combining the AJCC/IUAC TNM staging system with a postoperative clinicopathological staging system to predict both mortality risk and recurrence risk, with ongoing risk stratification based on response to therapy.

Initial Risk Stratification Systems

• The American Joint Committee on Cancer/International Union Against Cancer (AJCC/IUAC) TNM staging system is the most widely used system for predicting mortality risk, primarily based on tumor extent and patient age 1
• While TNM staging effectively predicts cancer mortality, it fails to adequately predict the risk of recurrence, necessitating additional risk stratification approaches 1
• A postoperative clinicopathological staging system should be used alongside the AJCC staging to better predict recurrence risk and guide appropriate treatment decisions 1

Risk Categories for Treatment Planning

The European Consensus Report defines three risk categories to guide radioiodine ablation therapy:

Very Low Risk

• Unifocal intrathyroidal tumor (T1 ≤1 cm) 1
• No aggressive histology 1
• No local or distant metastases 1
• Complete surgical resection 1

Low Risk

• Intrathyroidal tumor (T1 >1 cm and T2) 1
• May have aggressive histology 1
• No local or distant metastases 1
• Less than total thyroidectomy 1

High Risk

• Intrathyroidal tumor (T3) or micro/macroscopic invasion (T3-T4) 1
• Locoregional metastases 1
• Incomplete tumor resection 1

Modern Risk Stratification Approach

More recent guidelines have expanded risk stratification to include:

Intermediate Risk (6%-20% recurrence risk)

• Microscopic invasion of perithyroidal soft tissues 1
• Vascular invasion 1
• Clinical N1 or pathological N1 disease (>5 involved lymph nodes, each <3 cm) 1, 2
• RAI-avid metastatic foci in the neck on first post-treatment scan 1

High Risk (>20% recurrence risk)

• Gross extrathyroidal extension 1
• Pathological N1 disease with nodal metastases >3 cm 1, 2
• Extranodal extension 1, 2
• Concomitant BRAF V600E and TERT mutations 1
• Distant metastases 1

Ongoing Risk Stratification

• Tuttle et al. proposed "ongoing risk stratification" based on response to therapy, which dynamically reclassifies patients over time 1
• Patients are categorized as having excellent, acceptable, or incomplete response to therapy 1

Response Categories

• Excellent response: Undetectable basal and stimulated Tg, negative AbTg, negative neck US - very low recurrence risk (<1% at 10 years) 1
• Acceptable response: Undetectable basal Tg, stimulated Tg <10 ng/ml, declining Tg trend, AbTg absent/declining, substantially negative neck US 1
• Incomplete response: Detectable basal/stimulated Tg, stable/rising Tg trend, structural disease present, persistent/recurrent RAI-avid disease 1

Follow-up Based on Risk Stratification

Short-term Follow-up (6-12 months)

• Physical examination, neck ultrasound, basal and rhTSH-stimulated serum Tg measurement 1
• Diagnostic whole-body scan may be omitted in low-risk patients with normal neck US and undetectable stimulated Tg 1

Long-term Follow-up

• Patients with excellent response: Annual physical examination and suppressed Tg value 1
• Patients with acceptable response: Closer follow-up with additional treatment only if disease progression 1
• Patients with incomplete response: Intensive follow-up with multiple imaging modalities and likely additional therapies 1

Special Considerations

• Hürthle cell carcinoma is now classified as a distinct type of differentiated thyroid cancer with potentially more aggressive behavior, especially when associated with extensive vascular invasion (>4 foci) 3
• Nodal metastases should be further stratified by size, number, and presence of extranodal extension, as these characteristics significantly impact recurrence risk 2
• The 8th edition of AJCC staging system (using 55 years as age cutoff) better reflects thyroid cancer biology and has resulted in downstaging of many patients 4

Common Pitfalls to Avoid

• Overtreatment of very low-risk disease, particularly papillary microcarcinomas, which have excellent prognosis (99% survival at 20 years) 5
• Failing to consider the size and number of lymph node metastases when assessing risk - even a single microscopic lymph node metastasis can inappropriately upstage a patient 2
• Not integrating response to therapy into ongoing risk assessment, which can lead to unnecessarily aggressive long-term management 6
• Overlooking the integration of molecular markers (BRAF V600E, TERT mutations) into risk assessment, which can provide additional prognostic information 1, 7