What is the recommended staging system for thyroid cancer?

Thyroid Cancer Staging

The American Joint Committee on Cancer/International Union Against Cancer (AJCC/IUAC) TNM staging system is the recommended staging system for thyroid cancer. 1

TNM Staging System Overview

• The AJCC/IUAC TNM staging system is the most widely used and provides good risk stratification based on data available shortly after initial therapy 1
• The system primarily bases staging on tumor extent and patient age to predict mortality risk 1, 2
• The eighth edition of the TNM classification (effective January 2010) introduced important changes, including downstaging of extrathyroidal extension that is not macroscopically evident 1
• For medullary thyroid cancer (MTC), the TNM criteria are based on tumor size, presence/absence of extrathyroidal invasion, locoregional nodal metastases, and distant metastases 1

Limitations of TNM Staging

• While the TNM system effectively predicts mortality risk, it fails to predict the risk of recurrence 1, 2
• For MTC, the TNM staging lacks other important prognostic factors such as age at diagnosis, which significantly affects survival rates 1
• Patients younger than 40 years at MTC diagnosis have 5- and 10-year disease-specific survival rates of approximately 95% and 75%, respectively, compared with 65% and 50% for those older than 40 years 1

Supplementary Risk Stratification Systems

• A postoperative clinicopathological staging system should be used in conjunction with the AJCC staging system to improve prediction of recurrence risk 1, 2
• The European Consensus Report defines three risk categories to establish indications for radioiodine ablation therapy 1:
  • Very low risk: unifocal T1 (≤1 cm) N0 M0, no aggressive histology, no metastases, complete surgery 1, 2
  • Low risk: intrathyroidal tumor (T1 >1 cm and T2), aggressive histology possible, no metastases, less than total thyroidectomy 1, 2
  • High risk: intrathyroidal tumor (T3), micro/macroscopic invasion (T3-T4), locoregional metastases, incomplete tumor resection 1, 2

Ongoing Risk Stratification

• The concept of "Ongoing Risk Stratification" or "Delayed Risk Stratification" better defines patient risk based on treatment results 1, 2
• This approach continuously integrates the initial risk stratification with clinical, radiologic, and laboratory data collected during follow-up 1, 2
• Patients can be classified as having excellent, acceptable, or incomplete response to therapy 1, 2:
  • Excellent response: undetectable basal and stimulated thyroglobulin (Tg), negative anti-Tg antibodies, negative neck ultrasound 1, 2
  • Acceptable response: undetectable basal Tg, stimulated Tg <10 ng/ml, declining Tg trend 1, 2
  • Incomplete response: detectable basal/stimulated Tg, stable/rising Tg trend, structural disease present 1, 2

Special Considerations for Different Thyroid Cancer Types

• For medullary thyroid carcinoma, postoperative calcitonin (CTN) and carcinoembryonic antigen (CEA) levels should be documented as additional prognostic factors 1, 3
• Doubling times for postoperative serum calcitonin and CEA levels are established prognostic markers in MTC 1, 3
• For Hürthle cell carcinoma, the presence of extensive vascular invasion (>4 foci) indicates more aggressive behavior requiring closer monitoring 1, 2
• Molecular markers such as BRAF V600E and TERT mutations provide additional prognostic information and may influence risk stratification 1, 2

Clinical Implications and Follow-up

• The response to initial therapy significantly impacts long-term follow-up protocols 1, 2
• Patients with excellent response have very low recurrence risk (<1% at 10 years) and can be followed with yearly physical examination and suppressed Tg value 1, 2
• Patients with acceptable response require closer follow-up but additional treatment only if disease progression occurs 1, 2
• Patients with incomplete response need intensive follow-up with multiple imaging modalities and likely additional therapies 1, 2

Common Pitfalls in Thyroid Cancer Staging

• Downstaging in the newer TNM editions may lead to underestimation of disease severity, especially in the 45-55 year age group and stage II patients 4
• When switching from the seventh to eighth edition TNM system, more recurrences were observed in stages II and III, with recurrence risk in stage II increasing from 29% to 76% 4
• Focusing solely on TNM staging without considering additional risk factors may lead to inadequate treatment and follow-up planning 1, 2
• For MTC, failure to consider age at diagnosis and postoperative calcitonin levels may result in inaccurate prognostication 1, 3