Surgical Management

Surgical Management

Clinical Outline

Educational Clips from TIROxMDS

1. Initial Treatment: Thyroidectomy

2. Initial Treatment: Neck Dissection

A. Patients Clinically N0, Preoperatively cN0

B. Patients Clinically N1, Preoperatively cN1

3. Management of Patients With Locally Advanced or Metastatic Disease

A. Treatment of Locally Advanced Disease

B. Local Therapy for Patients with Distant Metastases

C. Management of Patients with Incomplete Thyroidectomy and/or Lymph Node Dissection Incomplete Initial Surgery

4. Evaluation of Patients Following Surgery Including Measurement of Ctn & CEA and Scans for Workup of Rising Ctn & CEA

A. Evaluation of Patients Following Surgery

B. Measurement of Doubling Times of Serum Ctn & CEA to Determine Rate of Disease Progression

= Primers in Thyroidology

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= Grand Rounds Lectureship

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Management Recommendations

1. Initial Treatment: Thyroidectomy

ATA // ESMO // JAES // NCCN

Total thyroidectomy is recommended as initial treatment in all patients.^​1–3​

Unilateral sporadic MTC may be treated by thyroid lobectomy.^​4​

It is recommended to:

• Treat pheochromocytoma before treating MTC.^​1,2​
• Treat hyperparathyroidism at time of thyroidectomy.^​1​
• Perform a preoperative ultrasound of the thyroid and neck.^​1–4​

2. Initial Treatment: Neck Dissection

When indicated, neck dissection should be performed by an experienced surgeon.^​3​

A. Patients Clinically N0, Preoperatively cN0

Prophylactic central neck dissection in patients cN0 on initial imaging is generally recommended, but with varying criteria and thresholds for indications.

A prophylactic lateral neck dissection is recommended ipsilaterally:

• By ESMO if basal Ctn > 50 pg/ml and bilaterally if basal Ctn > 200 pg/ml,^​3​
• By ATA and JAES based on basal serum Ctn.^​1,4​

B. Patients Clinically N1, Preoperatively cN1

A therapeutic neck dissection is recommended in patients with cN1 on initial imaging:

• It is recommended to perform a central neck dissection (level VI) in all patients with metastatic nodes detected preoperatively (cN1a or cN1b).^​1–4​

Extent of central neck dissection in clinically N1 disease preoperatively:

• ESMO and NCCN recommend bilateral prophylactic level VI neck dissection.
• ATA and JAES do not indicate whether prophylactic neck dissection of level VI should be bilateral or unilateral.

It is recommended to perform a therapeutic ipsilateral lateral neck dissection for cN1b patients. The extent of the therapeutic lateral neck dissection differs among the guidelines:

• The ATA recommends neck dissection of the involved lateral neck compartments (levels II-V).
• The NCCN recommends a modified neck dissection (levels II-V). 
• The ESMO recommends neck dissection of at least levels IIA, III and IV.
• The JAES does not have a recommendation regarding therapeutic lateral neck dissection.

EXPERT COMMENTARY NEEDED – BY MLU comment

A prophylactic ipsilateral lateral neck dissection may be considered in cases of high-volume or gross disease in the ipsilateral central compartment (high-volume cN1a)^​2​ or based on Ctn levels and “prognostic factors individually”.^​4​

A prophylactic contralateral lateral neck dissection should be considered for unilateral cN1b patients if basal Ctn > 200 pg/ml. 

3. Management of Patients With Locally Advanced or Metastatic Disease

A. Treatment of Locally Advanced Disease

For unresectable disease, EBRT/IMRT or systemic therapy may be considered.^​1,2​

When surgery is possible, function-sparing techniques and techniques that minimize complications should be preferred when possible. EBRT/IMRT and/or systemic adjuvant therapies may be considered.^​1,2​

Radical neck dissection is not recommended.^​2​

Adjuvant radiation therapy to the neck Is rarely recommended by the NCCN but may be considered after grossly incomplete tumor resection after additional attempts at surgical resection have been ruled out^​2​ or in the presence of extensive regional or metastatic disease after less aggressive surgery with preservation of voice and swallowing has been performed.^​1​

The decision for surgery, external beam radiation therapy (EBRT) and/or systemic therapy should be discussed in a multidisciplinary setting and the patient included in the decision-making process.^​1​

i. Factors to Consider in the Decision

ATA // ESMO

• Disease related symptoms.
• Ability to preserve function (speech, swallowing).
• Rate of disease progression.
• Life expectancy and comorbidities. 

B. Local Therapy for Patients with Distant Metastases

Locoregional therapy in patients with distant metastases may be considered based on symptoms and disease progression.^​1,3​ Function-sparing techniques are preferred. Less aggressive surgery may be appropriate, with or without EBRT and/or systemic therapy.^​1​

C. Management of Patients with Incomplete Thyroidectomy and/or Lymph Node Dissection Incomplete Initial Surgery

i. After Thyroid Lobectomy

If a germline RET mutation is found, a completion thyroidectomy and neck dissection are indicated, tailored according to the neck ultrasound and calcitonin levels, following the recommendations for initial surgery. (See initial surgery)^​1–3​

In the absence of germline RET mutation, if the postoperative basal Ctn is undetectable and CEA is normal, only follow-up is required.^​2​ Otherwise, treatment should follow recommendations for initial surgery.

ii. After Incomplete Lymph Node Dissection

If the postoperative basal Ctn is detectable, the NCCN recommends performing imaging work-up, adding contrast enhanced neck, chest and liver CT if Ctn  > 150 pg/ml. Surgery is the preferred modality for treatment of locoregional persistent disease.^​2​

After incomplete initial neck dissection, the ATA recommends considering a repeat neck dissection only if the postoperative basal Ctn < 1000 pg/ml and five or fewer lymph nodes had been removed in the previous operation, regardless of RET mutation status.^​1​

4. Evaluation of Patients Following Surgery Including Measurement of Ctn & CEA and Scans for Workup of Rising Ctn & CEA

A. Evaluation of Patients Following Surgery

i. Post-surgical Follow-up Planning

ATA // ESMO // NCCN

Post-operative TNM classification, extent of lymph node metastases, and postoperative serum Ctn levels should be considered in predicting outcome and planning long-term follow-up of patients treated by thyroidectomy for MTC.

ii. Frequency of Post-surgical Ctn & CEA Monitoring

ATA // ESMO // NCCN

Initial assessment of Ctn and CEA serum levels should be measured 2–3 months postoperatively. If undetectable or within the normal range, they should be tested every 6 months for 1 year and then yearly thereafter. The likelihood of significant residual disease with an undetectable basal Ctn is very low.

If the patient has MEN2 then annual screening for pheochromocytoma (MEN2B or MEN2A) and hyperparathyroidism (MEN2A) should also be performed.

iii. Approach if elevated Ctn < 150 pg/ml

ATA // ESMO // NCCN

Patients with elevated postoperative serum Ctn levels less than 150 pg/mL should have a physical examination and US of the neck. If these studies are negative the patients should be followed every 6 months (or 6–12 months NCCN) with physical examination, measurement of serum levels of Ctn and CEA, and US.

iv. Approach if Ctn > 150 pg/ml

ATA // ESMO // NCCN

If the postoperative serum Ctn level exceeds 150 pg/mL patients should be assessed with multiple imaging procedures as required, including neck US, chest CT, contrast-enhanced MRI or three-phase contrast-enhanced CT of the liver, and bone scintigraphy and/or MRI of the pelvis and axial skeleton.

If these initial investigations are negative, there is some discordance between guideline recommendations with regard to the appropriate tests to use in order to identify structural disease recurrence:

• FDG PET and FDOPA PET/CT are not recommended to detect distant metastases.^​1​
• FDG PET/CT may be useful in assessing advanced disease and disease demonstrating rapid progression based on rapid calcitonin /CEA doubling times.^​2,3​
• FDOPA PET/CT has high specificity and sensitivity in MTC and may be useful in detection of small lesions that are not detected by other imaging modalities. However high cost and lack of availability represent challenges to access for patients.^​3​
• 68Ga-DOTATATE PET may be considered as an additional imaging study if initial imaging is negative.^​2​
• 68Ga-somatostatin analogue PET should be considered when feasibility of radionuclide therapy is being explored.^​3​

B. Measurement of Doubling Times of Serum Ctn & CEA to Determine Rate of Disease Progression

i. Ctn Doubling Time Calculation

ATA // ESMO // NCCN

In patients with detectable serum levels of Ctn and CEA following thyroidectomy, these markers should be measured at least every 6 months to determine their doubling times.^​1​ These should be based on at least four consecutive measurements, preferably over a 2-year period.^​3​

ii. Utility of Ctn Doubling Time to Guide Systemic Therapy

ATA // ESMO // NCCN

Systemic therapy should not be administered to patients with increasing serum Ctn and CEA levels but no documented metastatic disease^​1​ or absence of structural disease progression.^​2​ Nor should systemic therapy be administered to patients with stable low-volume metastatic disease, as determined by imaging studies and serum Ctn and CEA doubling times greater than 2 years. Clinically relevant disease is rarely detected if Ctn < 150pg/ml, but the likelihood of structural disease increases as Ctn, and CEA levels rise.^​3​

iii. Exclusion of Distant Disease Prior to Repeat Neck Surgery

ATA // ESMO // NCCN

Distant metastatic disease should be excluded prior to repeat neck surgery. Most guidelines^​2,3​ advocate the use of conventional imaging +/- selective use of PET scanning (see ‘Approach if Ctn > 150 pg/ml’) in patients with persistent or recurrent MTC following thyroidectomy.

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