What is the difference in management between papillary (Papillary Thyroid Cancer) and follicular (Follicular Thyroid Cancer) thyroid cancer after surgery?

Management Differences Between Papillary and Follicular Thyroid Cancer After Surgery

The post-surgical management of papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) follows similar principles based on risk stratification, though FTC generally requires more aggressive radioactive iodine (RAI) therapy due to its tendency for hematogenous spread.

Histological Differences Impacting Management

Papillary Thyroid Cancer

• Accounts for approximately 80% of thyroid cancers 1
• Characterized by lymphatic spread pattern
• Often multifocal (can occur in multiple areas of thyroid)
• Better overall prognosis compared to FTC
• Molecular profile often includes BRAF V600E, RET/PTC fusions 1

Follicular Thyroid Cancer

• Accounts for approximately 11% of thyroid cancers 1
• Characterized by hematogenous spread (blood vessels)
• More likely to have vascular invasion
• Higher rates of distant metastases at diagnosis 2
• Molecular profile often includes RAS mutations, PAX8/PPARγ fusions 1

Risk Stratification System

Both PTC and FTC use the same risk stratification system, which guides post-surgical management:

• Low risk (≤5%): Intrathyroidal tumor ≤4 cm, no aggressive histology, no vascular invasion 1, 3
• Intermediate risk (6-20%): Microscopic extrathyroidal extension, aggressive histology, vascular invasion, N1 disease 1, 3
• High risk (>20%): Gross extrathyroidal extension, incomplete resection, distant metastases 1, 3

Radioactive Iodine (RAI) Therapy Differences

Papillary Thyroid Cancer

• Low-risk microcarcinomas (<1 cm): RAI generally not indicated 1
• Low-risk (1-4 cm): Selective use of RAI based on other risk factors
• Intermediate-risk: RAI typically recommended
• High-risk: RAI strongly recommended

Follicular Thyroid Cancer

• RAI is more consistently recommended for FTC, even in lower-risk cases due to:
  • Higher propensity for hematogenous spread
  • More difficult to detect metastases with ultrasound alone
  • Higher rates of distant metastases 2, 4
• Doses of 30-100 mCi are typically used based on extent of disease 1

TSH Suppression Therapy

Papillary Thyroid Cancer

• Low-risk: Target TSH 0.5-2.0 μIU/mL 3
• Intermediate-risk: Target TSH 0.1-0.5 μIU/mL 3
• High-risk: Target TSH <0.1 μIU/mL 3

Follicular Thyroid Cancer

• Generally requires more aggressive TSH suppression
• Even low-risk FTC: Often managed with target TSH in lower range
• Intermediate to high-risk: Target TSH <0.1 μIU/mL 1, 3

Follow-up Protocol Differences

Papillary Thyroid Cancer

• Neck ultrasound at 6-12 months, then annually if stable
• Serum thyroglobulin measurements
• Less frequent imaging of distant sites unless high-risk features

Follicular Thyroid Cancer

• Similar neck ultrasound and thyroglobulin monitoring
• More comprehensive imaging may be warranted:
  • More frequent whole-body scans
  • Earlier consideration of CT/MRI for distant metastasis evaluation
  • Closer attention to bone and lung metastases 2

Advanced Disease Management

For radioiodine-refractory disease:

• Lenvatinib: FDA-approved for both PTC and FTC with locally recurrent or metastatic, progressive disease 5

  • Demonstrated significant PFS improvement (18.3 vs 3.6 months)
  • 65% objective response rate vs 2% with placebo

• Sorafenib: Also approved for radioiodine-refractory differentiated thyroid cancer 6

  • Median PFS 10.8 months vs 5.8 months with placebo

Key Considerations and Pitfalls

1. Avoid overtreatment of low-risk disease: Particularly for papillary microcarcinomas, which have excellent prognosis without RAI 1

2. Recognize the importance of histologic variants:

   • Aggressive PTC variants (tall cell, columnar, hobnail) require more intensive treatment
   • Minimally invasive FTC has better prognosis than widely invasive FTC 1

3. Hürthle cell carcinoma: Previously classified as FTC variant, now considered a distinct entity with potentially more aggressive behavior 1

4. Surgical expertise matters: Complication rates are four times higher with less experienced surgeons 3

5. NIFTP consideration: Non-invasive follicular thyroid neoplasm with papillary-like nuclear features is now considered a separate entity with excellent prognosis, not requiring RAI 1

Dynamic Risk Stratification

For both PTC and FTC, initial risk assessment should be revised during follow-up based on response to therapy 1:

• Excellent response: No clinical, biochemical, or structural evidence of disease
• Biochemical incomplete: Abnormal thyroglobulin, no structural disease
• Structural incomplete: Persistent/recurrent structural disease
• Indeterminate: Nonspecific findings that cannot be classified

The long-term management approach should be adjusted based on this dynamic risk assessment, with more intensive surveillance and treatment for those with incomplete responses.