Management of Patients with Anaplastic Thyroid Cancer

Publication Date: March 20, 2021
Last Updated: August 3, 2023


Cytology, Histopathology, And Differential Diagnosis

Recommendation 1

FNA cytology can play an important diagnostic role in the initial evaluation of ATC, but parallel core biopsy may be necessary for definitive diagnosis and to obtain sufficient material for molecular interrogation. (S, L)

Recommendation 2

Every effort should be made to establish a diagnosis via biopsy before proceeding with surgical resection, as surgical resection may be inappropriate. (S, L)

Recommendation 3

Routine surgical pathology evaluation of resection specimens should focus on confirming a definitive diagnosis of ATC, documenting extent of disease, and defining the presence of any coexisting DTC and/or other pathologies. The proportion of tumor that represents ATC should also be documented. (S, L)

Recommendation 4

Once ATC diagnosis is considered, assessment of BRAFV600E mutation should be expeditiously performed by IHC and confirmed/expeditiously assessed by molecular testing. (S, M)

Recommendation 5

Molecular profiling should be performed at the time of ATC diagnosis to inform decisions related to the use of targeted therapies, especially as there are now FDA-approved mutation-specific therapies in this context. (S, M)

Initial Evaluations

Recommendation 6

Initial radiological tumor staging should include cross-sectional imaging, in particular, CT neck, chest, abdomen, and pelvis with contrast (or MRI), and, if available, FDG PET/CT. Contrast-enhanced imaging of the brain (MRI preferred) should also be performed, if clinically indicated. (S, M)

Good Practice Statement 1

In the event that biopsy of a suspected metastatic disease site is clinically indicated, primary management of ATC should not be delayed until biopsy is obtained. (GPS, )

Good Practice Statement 2

All critical appointments and assessments that are required before primary treatment of ATC should be prioritized and completed as rapidly as possible. (GPS, )

Recommendation 7

Every patient with ATC should undergo evaluation of the vocal cords at initial presentation, and thereafter based upon changing symptoms. (S, L)


Establishing Goals of Care

Recommendation 8

Comprehensive disease-specific multidisciplinary input should be attained before defining “goals of care” or undertaking therapeutic discussions with patients. Those involved in management decisions should include specialists highly experienced in treating ATC. (S, L)

Good Practice Statement 3

Patients must have understanding and decision-making capacity to consent to treatment or to make particular medical decisions. Concerns about diminished or impaired capacity should prompt mental health and/or clinical ethics consultation to assess barriers to capacity. (GPS, )

Good Practice Statement 4

Patients should be encouraged to draft both an advance directive in which they name a surrogate decision maker and list code status and other end-of-life preferences including POLST or MOST document. Circumstances where suspension of DNR may occur must be discussed with the patient as well. (GPS, )

Good Practice Statement 5

A “goals-of-care” discussion should be initiated with the patient as soon as possible. In consultation with a multidisciplinary team, a candid session should be conducted in which there is full disclosure of the potential risks and benefits of various treatment options, updated frequently, including how such options will impact the patient’s life. Treatment options discussed should include all end-of-life options, such as hospice and palliative care. Patient preferences should guide clinical management. (GPS, )

Recommendation 9

The treatment team should include palliative care expertise at every stage of patient management to help with pain and symptom control, as well as addressing psychosocial and spiritual issues. (S, L)

Recommendation 10

The treatment team should engage hospice care for ATC patients who decline therapies against their tumor intending to prolong life, yet who still require symptom and pain relief spanning the remainder of their illness. (S, L)

Recommendation 11

At all stages of palliative care and hospice care in ATC patients, practitioners should be aware of family systems, and how they affect patient decision-making. (S, L)

Surgical Management of ATC

Recommendation 12

For patients with confined (stage IVA/IVB) ATC in whom R0/R1 resection is anticipated, we strongly recommend surgical resection.
  • Value Statement: The authors for this recommendation placed a higher value for the benefit (longer overall survival) of surgical resection and placed a lower value for potential morbidity and subsequent delay in chemotherapy and/or radiation therapy.
(S, L)

Recommendation 13

Radical resection (including laryngectomy, tracheal resections, esophageal resections, and/or major vascular or mediastinal resections) is generally not recommended given the poor prognosis of ATC and should be considered only very selectively after thorough discussion by the multidisciplinary team, also considered in light of new information based upon mutations present and the availability of targeted therapies. (S, L)

Good Practice Statement 6

If surgery is undertaken, intraoperative frozen section and pathology consultation may be a helpful adjunct to inform surgical decision-making. (GPS, )

Good Practice Statement 7

In patients without impending airway compromise, we advise against preemptive tracheostomy placement. (GPS, )

Radiotherapy and Systemic Chemotherapy in Locoregionally-confined (Stages IVA and IVB) ATC: Principles and Approaches

Recommendation 14

Following R0 or R1 resection, the ATA recommends that good performance status patients with no evidence of metastatic disease who wish an aggressive approach should be offered standard fractionation IMRT with concurrent systemic therapy. (S, L)

Good Practice Statement 8

Radiation therapy should begin no later than 6 weeks after surgery. (, )

Good Practice Statement 9

Patient goals of care, medical and psychosocial fitness for therapy, potential toxicities, financial considerations, and robustness of social support must be prominently considered in the decision to proceed with aggressive multimodal therapy. (, )

Good Practice Statement 10

Cytotoxic chemotherapy can be initiated within 1 week of surgery, providing sufficient healing, in anticipation of subsequent chemoradiation. (, )

Recommendation 15

The ATA recommends that patients who have undergone R2 resection or have unresectable but nonmetastatic disease with good performance status and who wish an aggressive approach be offered standard fractionation IMRT with systemic therapy. Alternatively, in BRAFV600E-mutated ATC, combined BRAF/MEK inhibitors can be considered in this context. (S, L)

Recommendation 16

In patients with unresectable disease during initial evaluation in whom radiotherapy and/or systemic (chemotherapy or combined BRAF/MEK inhibitors) therapy render the tumor potentially resectable, the ATA recommends reconsideration of surgical resection. (S, L)

Good Practice Statement 11

In patients of poor performance status, palliative or preventative (no residual disease present) locoregional radiotherapy over high dose radiotherapy is suggested. (GPS, )

Recommendation 17

Among patients who are to receive radiotherapy for unresectable thyroid cancer or in the postoperative setting, IMRT is recommended. (S, L)

Recommendation 18

The use of cytotoxic chemotherapy involving a taxane (paclitaxel or docetaxel), administered with or without anthracyclines (doxorubicin) or platin (cisplatin or carboplatin), is recommended in patients treated with definitive-intention radiation. (S, L)

Systemic Therapeutic Approaches to Locally Advanced Unresectable and/or Metastatic Disease

Recommendation 19

Among ATC patients with unresectable or advanced disease wishing aggressive therapy, the ATA suggests early initiation of cytotoxic chemotherapy as an initial and potentially bridging approach until mutational interrogation results and/or mutationally specified therapies might be available, and if appropriate. (C, L)

Recommendation 20

In BRAFV600E-mutated IVC and in unresectable IVB ATC patients who decline radiation therapy, initiation of BRAF/MEK inhibitors (dabrafenib plus trametinib) is recommended over other systemic therapies if available. (S, L)
  • Value Statement: The authors—including patient advocates—for this recommendation placed a high value on available and emerging data indicating the potential for profound benefit from using this approach in a setting where little hope had previously existed, supporting the strong recommendation made in the presence of low-quality evidence.

Recommendation 21

In BRAFV600E-mutated unresectable stage IVB ATC in which radiation therapy is feasible, chemoradiotherapy or neoadjuvant dabrafenib/trametinib represents alternatives to initial therapy. (C, L)

Recommendation 22

In BRAF non-mutated patients, radiation therapy with concurrent chemotherapy should be considered in an effort to maintain the airway in patients with low burden of metastatic disease. (S, L)

Recommendation 23

In NTRK or RET fusion ATC patients with stage IVC disease, the ATA suggests initiation of a TRK inhibitor (either larotrectinib or entrectinib) or RET inhibitor (either selpercatinib or pralsetinib), preferably in a clinical trial, if available. (C, VL)

Recommendation 24

In IVC ATC patients with high PD-L1 expression, checkpoint (PD-L1, PD1) inhibitors can be considered first-line therapy in the absence of other targetable alterations or as later line therapy, preferably in the context of a clinical trial. (C, L)

Good Practice Statement 12

Patients with BRAF wild-type (BRAF “negative” or unknown mutation status) IVB unresectable or metastatic ATC wishing an aggressive approach and not receiving chemoradiation should be encouraged to participate in clinical trials given the rarity of ATC, the paucity of data in support of improved survival or quality of life from any systemic therapeutics, and the need to develop evidence-based safe and effective therapeutic approaches in advanced ATC. (GPS, )

Recommendation 25

In metastatic ATC patients lacking other therapeutic options including clinical trials, the ATA suggests cytotoxic chemotherapy including a taxane and/or an anthracycline or taxane with or without cis- or carbo-platin. (C, L)

Good Practice Statement 13

Therapeutic decision-making in the setting of PD after initial therapy regardless of somatic mutational status or therapy is very complex and not easily defined by an algorithmic approach. In this setting, care guided by an expert in ATC therapeutics is best pursued. (GPS, )

Good Practice Statement 14

Since prognosis is dire in metastatic and progressive ATC, best supportive care (hospice) should also be discussed as an option. (GPS, )

Recommendation 26

In ATC patients considering therapy, the ATA recommends brain MRI assessing the presence of brain metastases at time of diagnosis as a part of initial staging and when symptoms otherwise prompt concern. (S, L)

Recommendation 27

In ATC patients with neurologic brain compressive symptoms or signs, the ATA recommends dexamethasone (4–16 mg/day). (S, L)

Recommendation 28

In ATC patients with brain metastases referral to neurosurgery/radiation oncology should be made. (S, L)

Good Practice Statement 15

Patients with brain metastases may be expected to be at increased risk if operating motor vehicles or if placed in a situation in which they may jeopardize themselves or others and therefore should be appropriately counseled. (GPS, )

Approaches to Bone Metastases

Recommendation 29

In patients with ATC with symptomatic or threatening bone metastases—but without structural compromise or threatened spinal cord compression in need of surgical remediation—the ATA recommends palliative radiotherapy. (S, L)

Recommendation 30

In patients with ATC with bone metastasis causing structural compromise in a weight-bearing region or threatening spinal cord compression, the ATA recommends orthopedic fixation before initiation of palliative radiotherapy. (S, L)

Recommendation 31

In patients with ATC with bone metastasis, the ATA suggests periodic intravenous bisphosphonate infusions or subcutaneous RANK ligand inhibitor. (C, L)

Good Practice Statement 16

In patients on systemic therapy who develop oligo-progressive disease, local tumor-directed therapy may be considered to postpone the need to change otherwise beneficial systemic therapy. (GPS, )

Approaches to Other Sites of Metastases

Systemic therapy as described above is the first line of treatment, but if a particular metastasis is symptomatic or has progressed despite systemic therapy, treatment may be individualized to metastatic locations, much as would be the case for other malignancies (N) (, )

Approaches to Oligoprogressive Metastatic Disease

Good Practice Statement 16

In patients on systemic therapy who develop oligo-progressive disease, local tumor-directed therapy may be considered to postpone the need to change otherwise beneficial systemic therapy. (GPS, )

Recommendation Grading



Management of Patients with Anaplastic Thyroid Cancer

Authoring Organization

Publication Month/Year

March 20, 2021

Last Updated Month/Year

February 6, 2024

Document Type


External Publication Status


Country of Publication


Inclusion Criteria

Male, Female, Adult, Older adult

Health Care Settings

Ambulatory, Hospital, Outpatient, Radiology services

Intended Users

Nurse, nurse practitioner, physician, physician assistant


Counseling, Diagnosis, Assessment and screening, Treatment, Management

Diseases/Conditions (MeSH)

D065646 - Thyroid Carcinoma, Anaplastic


anaplastic thyroid cancer

Source Citation

Bible KC, Kebebew E, Brierley J, Brito JP, Cabanillas ME, Clark TJ Jr, Di Cristofano A, Foote R, Giordano T, Kasperbauer J, Newbold K, Nikiforov YE, Randolph G, Rosenthal MS, Sawka AM, Shah M, Shaha A, Smallridge R, Wong-Clark CK. 2021 American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer. Thyroid. 2021 Mar;31(3):337-386. doi: 10.1089/thy.2020.0944. Erratum in: Thyroid. 2021 Oct;31(10):1606-1607. PMID: 33728999; PMCID: PMC8349723.


Number of Source Documents
Literature Search Start Date
February 15, 2017
Literature Search End Date
May 11, 2020