2021 Philippine Interim Clinical Practice Guidelines (CPG) for the Diagnosis and Management of Well-Differentiated Thyroid Cancer

Erick S. Mendoza, MD, MBAH, FPCP, FPCEDMErick S. Mendoza, MD, MBAH, FPCP, FPCEDM

Thyroid cancer is considered the most common endocrine cancer in the Philippines. It is the 6th most common cancer among Filipinos with a 5-year prevalence of 19,260 cases. It ranks 21st in terms of mortality based on the 2020 data. Under the National Integrated Cancer Control Act (RA 11215) of 2019,  it seeks to “prevent cancer, improve cancer survivorship and make cancer care and treatment equitable and available to all Filipinos,”  through the National Integrated Cancer Control Council. Among the latter’s roles is to develop, update and promote evidence-based treatment standards and guidelines for cancer of all ages and stages.

Although there are several international guidelines available, they may not be applicable in the local setting due to cost and availability. The Department of Health called for the development  of a national guideline on thyroid cancer to address the needs of afflicted Filipino patients and aid the Filipino physicians in decision-making. At large, this can be used as a basis for benefit packages of Philippine Health Insurance Corporation as we embrace the implementation of the Universal Health Coverage law.

The 2021 Philippine Interim Clinical Practice Guidelines (CPG) for the Diagnosis and Management of Well-Differentiated Thyroid Cancer (WDTC)was commissioned by DOH to Dr. Jose R. Reyes Memorial Medical Center as the lead developer and Dr. Ida Marie T. Lim as the project leader along with the steering committee, technical working group and consensus panel.

The CPG presented recommendations on the screening, diagnosis, surgical and postoperative management, surveillance and palliative care of well-differentiated thyroid cancer. The summary of the recommendations are as follow:

Screening. The task force recommended screening high risk but not asymptomatic individuals for thyroid cancer. The risk factors included history of significant exposure to ionizing radiation to the head and neck area, inherited genetic syndromes associated with thyroid cancer or first-degree relative with history of thyroid cancer. The recommended screening is systematic neck palpation and ultrasound, however, the former alone is sufficient for low resource settings.

Diagnosis and preoperative evaluation. The task force recommended serum TSH and neck ultrasound with cervical lymph node assessment in all patients suspected to have malignant thyroid nodules. Fine needle aspiration biopsy (FNAB) should be performed on all nodules suspected of being malignant based on clinical or US findings. The manner of cytology report should be utilizing The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). Molecular testing may be considered for indeterminate FNAB, particularly for Bethesda III and IV. The use of CT or MRI may be considered in clinically advanced cases like bulky and fixed tumors. There are also features that will require vocal fold visualization.

Surgical Management. The task force recommended total thyroidectomy for Bethesda Category V and VI (suspicious for malignancy and malignant) nodules measuring >1cm. Lobectomy and isthmusectomy may be performed at the minimum for Bethesda Category IV (follicular neoplasm or suspicious for follicular neoplasm). Therapeutic central neck dissection(Level VI)  is recommended if there is central compartment involvement, while both therapeutic central and posterolateral (Level II-V) neck dissection are recommended if there is ipsilateral compartment involvement. Surgical excision of extensive and metastatic disease are still recommended as long as there would be no adverse functional outcome. Although not routinely recommended, frozen sections may be considered in confirmation of extrathyroidal extension, confirmation of malignancy if it will alter the extent of surgical plan and confirmation of the nature of equivocal structures. Completion thyroidectomy is recommended in  the following instances: unanticipated malignancy with a tumor >1 cm, confirmed contralateral malignancy, confirmed nodal metastasis are an aggressive histologic type.

Postoperative management. The task force recommended AJCC/IUCC staging for all patients to standardize registry and predict mortality. On the other hand, the ATA risk stratification is used to guide further treatment. Radioactive iodine (RAI) therapy is recommended for both ATA high and intermediate risk individuals. Routine RAI is not recommended for ATA low risk, unifocal or multifocal papillary microcarcinoma without adverse features. RAI should be given after TSH stimulation (>30 mIU/mL) or after rTSH administration and followed by a whole body scan to stage the disease and document any iodine avid lesion. The degree of TSH suppression varies based on the initial ATA risk (<0.1 mU/L for high risk, 0.1-0.5 mU/L for intermediate risk and 0.5-2 mU/L for low risk with undetectable thyroglobulin). Targeted treatment is not routinely recommended in the adjuvant setting but may be considered especially in the presence of mutations and genetic aberrations, if accessible to such testing.

Surveillance. The task force recommended the modified ATA dynamic risk stratification to classify the response to therapy. The initial stratification should be determined within 6  months of treatment. Thyroglobulin (Tg) and anti-thyroglobulin (anti-Tg) assays to be used should be calibrated against a reference standard and should be performed every 3 to 6 months in the first year after treatment. Tg and anti-Tg measurement is recommended for patients who have undergone total thyroidectomy with or without radioactive iodine therapy but not for patients who have not undergone total thyroidectomy. Neck ultrasound should be performed at a 6 to 12-month interval depending on the risk assessment. Increasing the time interval for surveillance is recommended for those patients who already achieved excellent response. Unstimulated Tg with anti-Tg is sufficient initial test for patients with excellent response (high likelihood of negative result) and incomplete structural response (high likelihood of positive result). Diagnostic whole body scan is not routinely recommended among patients with negative Tg, anti-Tg and neck US. FDG-PET is recommended for high risk WDTC with elevated Tg but negative RAI imaging. CT or MRI are recommended in anatomic evaluation of metastatic disease.

Palliative care. The task force recommends a multidisciplinary team to address advanced disease stages. EBRT is recommended  in metastases such as spinal cord compression. In high resource settings, kinase inhibitors or immunotherapy is recommended for RAI-refractory metastatic disease. Otherwise, discussion and enrollment in clinical trials may be considered. The use of denosumab or bisphosphonates is recommended in patients with RAI-refractory disease with diffuse and/or symptomatic metastases. Cancer-related pain should be managed across all stages of disease.

The CPG will undergo regular review to incorporate new sets of evidence that will affect the recommendations and will be updated every 3 years.

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The PCEDM is a sub-specialty society of the Philippine College of Physicians, a founding member of the ASEAN Federation of Endocrine Societies, and a member of the International Society of Endocrinology.

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