What to do if calcitonin levels do not decrease to undetectable levels after treatment for Medullary Thyroid Cancer (MTC)?

Management of Persistent Elevated Calcitonin Levels After Medullary Thyroid Cancer Treatment

For patients with persistently elevated calcitonin levels after treatment for Medullary Thyroid Cancer (MTC), a structured surveillance approach with imaging studies and consideration of reoperation is recommended for locoregional disease, while observation is appropriate for those with no identifiable disease foci. 1

Initial Assessment (2-3 months post-surgery)

Evaluation of Calcitonin and CEA Levels

• Measure basal serum calcitonin and CEA 2-3 months postoperatively 1
• Interpret results:
  • Undetectable calcitonin: Excellent prognosis with 97-98% 10-year disease-free survival 2
  • Detectable calcitonin: Indicates residual disease in approximately 80% of patients with palpable MTC and 50% with nonpalpable but macroscopic MTC 1

Imaging Protocol for Detectable Calcitonin

1. Calcitonin <150 pg/ml:

   • Neck ultrasound (primary imaging modality) 1
   • Consider additional imaging as baseline for future comparison, though typically negative at this level 1

2. Calcitonin ≥150 pg/ml:

   • Comprehensive imaging is mandatory 1:
     • Contrast-enhanced CT or MRI of neck, chest, and abdomen with liver protocol
     • Bone scan, FDG-PET scan, or MRI of axial skeleton
     • Liver triphasic contrast-enhanced CT or MRI

Management Algorithm for Persistent Elevated Calcitonin

For Asymptomatic Patients with No Identifiable Disease

1. Conservative surveillance 1:

   • Monitor serum calcitonin and CEA every 6-12 months
   • More frequent testing if markers show significant rise
   • No therapeutic intervention based solely on abnormal markers outside clinical trials

2. For patients with incomplete primary surgery:

   • Consider cervical reoperation 1

For Patients with Identifiable Locoregional Disease

1. Surgical resection with or without postoperative radiotherapy if no distant metastases 1
2. Consider radiotherapy for symptomatic progressive or unresectable disease 1
   • Note: Radiotherapy results in calcitonin normalization in only about 4% of patients but can reduce local relapse rates (29% vs. 59%) 3

For Patients with Distant Metastases

1. Symptomatic metastases:

   • Clinical trial (preferred) 1
   • Palliative resection, ablation (radiofrequency, embolization), or other regional treatment 1
   • Consider small molecule kinase inhibitors (sorafenib or sunitinib) if clinical trials unavailable 1
   • Dacarbazine-based chemotherapy 1
   • Bisphosphonate therapy for bone metastases 1

2. Asymptomatic metastases:

   • Observation is acceptable 1
   • Consider intervention for progressive disease 1

Prognostic Considerations

• Calcitonin doubling time is a critical prognostic indicator 2:

  • 6 months: 92% 5-year survival

  • <6 months: 25% 5-year survival

• Undetectable vs. normalized calcitonin:

  • Patients with merely normalized (2-10 pg/ml) calcitonin have a 25% risk of recurrence
  • Patients with truly undetectable (<2 pg/ml) calcitonin have only a 3% risk of recurrence 4

• Timing of calcitonin normalization:

  • In patients destined to achieve undetectable calcitonin, 97% reach this level within 1 month after curative surgery 5
  • By 6 months, 100% of patients who will achieve biochemical cure have reached undetectable calcitonin levels 5

Important Caveats

1. Imaging limitations: Even with comprehensive imaging, approximately 10-18% of patients with elevated calcitonin will have no identifiable disease 6

2. Misleading markers: In aggressive MTC, calcitonin may decrease while CEA increases, so monitor both markers 2

3. Long-term prognosis: Despite persistent calcitonin elevation, patients can have favorable long-term survival (72% 10-year survival) with observation alone 3

4. Reoperation risks: Consider the risk-benefit ratio of reoperation, as routine lymphadenectomy or excision of palpable tumor often fails to normalize calcitonin 1

5. Surveillance duration: Long-term surveillance is essential as recurrence can occur even after years of stable disease 1