9. Discuss guidelines for follow-up post-thyroidectomy for cancer (labs/tests) HH

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1 9. Discuss guidelines for follow-up post-thyroidectomy for cancer (labs/tests) HH Differentiated thyroid cancer expresses the TSH receptor on the cell membrane and responds to TSH stimulation by increasing the expression of several thyroid specific proteins (Tg, sodium-iodide symporter). TSH suppression (<0.1mU/L) is recommended for high-risk and intermediate-risk thyroid cancer patients Serum Tg should be measured every 6-12 months with a quantitative assessment of thyroglobulin antibodies with every measurement. Serum Tg and neck U/S may be done in patients with less than total thyroidectomy or in patients with total thyroidectomy but no RAI to eval increase in Tg over time. Suspicious lymph nodes on f/u (>5-8mm) should have FNA with Tg measurement in the needle washout fluid. PET scans have traditionally been used in Tg +, RAI scan negative patients. They may also be useful in initial staging and follow up of high-risk patients with poorly differentiated thyroid cancers unlikely to concentrate iodine, in invasive/metastatic Hurthle cell carcinoma staging and follow up. Low risk patients are unlikely to require PET scan. From Cummings: In addition to regular physical examination, thyroid hormone and TSH levels are monitored to ensure adequate suppression. Thyroglobulin levels should be closely monitored, and diagnostic radioiodine scanning should be performed. These tests should be performed annually for the first 2 years and then every 5 years for 20 years. [275] Typically, thyroglobulin levels should be less than 2 ng/ml after total thyroidectomy and radioiodine ablation therapy (<3 ng/ml if the patient is off thyroid replacement therapy). Increasing serum thyroglobulin levels are highly sensitive (97%) and specific (100%) for thyroid cancer recurrence. [276] Elevation of thyroglobulin levels warrants repeat radioiodine scanning and therapy. More recent studies have shown the sensitivity of serum thyroglobulin measurements for predicting thyroid cancer recurrence after a patient has received two injections of recombinant human TSH. [277] Depending on risk classification, additional follow-up procedures vary. The 2006 ATA guidelines recommend measurement of serum thyroglobulin and a cervical ultrasound examination in low-risk patients approximately 12 months after initial treatment with surgery and radioiodine ablation, but not additional whole-body radioiodine scans. [69] In intermediate-risk and high-risk patients, cervical ultrasound examination and diagnostic whole-body radioiodine scans are recommended every 6 to 12 months. Patients with MTCs require serial measurements of calcitonin and CEA. Suspected recurrences may also be detected with pentagastrin-stimulation test.

1mU/L) is recommended for high-risk and intermediate-risk thyroid cancer patients Serum Tg should be measured every 6-12 months with a quantitative assessment of thyroglobulin antibodies with every

2 10. List prognostic factors (Ames criteria). HH From Cummings: Tumor Staging and Classification

3 Numerous staging and classification systems have been devised to stratify patients with thyroid carcinomas. These classifications have identified key patient-specific and tumor-specific characteristics that predict patient outcome. Risk-grouping has been used to focus aggressive treatment for high-risk patients and to avoid excessive treatment and its potential complications in patients with a lower risk for tumor recurrence or tumor-related death. TNM Classification The American Joint Commission on Cancer (AJCC) and the Union Internationale Contre le Cancer (UICC) adopted a tumor-node-metastasis (TNM) classification system (Table 124-1). In this system, patient age at presentation influences the clinical staging of a thyroid carcinoma. Of patients with stage I disease, 82% had a 20-year survival of nearly 100%, whereas the 5% of patients with stage IV disease experienced a 5-year survival of only 25%. [52] Table TNM Staging for Thyroid Cancer Primary Tumor (T) TX Primary tumor cannot be assessed T0 T1 T2 T3 T4a T4b No evidence of primary tumor Tumor = 2 cm in greatest dimension, limited to thyroid Tumor >2 cm and = 4 cm in greatest dimension, limited to thyroid Tumor >4 cm in greatest dimension, limited to the thyroid or Any tumor with minimal extrathyroid extension (e.g., extension to sternothyroid muscle or perithyroid soft tissues) Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues, larynx, trachea, esophagus, or recurrent laryngeal nerve Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels All Anaplastic Carcinomas Are Considered T4 Tumors T4a Intrathyroidal anaplastic carcinoma surgically resectable T4b Extrathyroidal anaplastic carcinoma surgically unresectable Regional Lymph Nodes (N) NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Regional lymph node metastasis N1a N1b Metastasis to level VI (pretracheal, paratracheal, and prelaryngeal/delphian lymph nodes) Metastasis to unilateral, bilateral, or contralateral cervical or superior mediastinal lymph nodes Distant Metastasis (M) MX Distant metastasis cannot be assessed M0 No distant metastasis M1 Distant metastasis Stage Grouping Age <45 Years Age 45 Years

Risk-grouping has been used to focus aggressive treatment for high-risk patients and to avoid excessive treatment and its potential complications in patients with a lower risk for tumor recurrence or

4 Stage Grouping Age <45 Years Age 45 Years Papillary/Follicular Stage I Any T any N M0 T1 N0 M0 Stage II T2 N0 M0 Stage III T3 N0 M0 T1-T3 N1a M0 T4a N0 M0 T4a N1a M0 T1-4a N1b M0 Medullary Stage I Stage II Stage III Anaplastic T1 N0 M0 T2 N0 M0 T3 N0 M0 T1-3 N1a M0 T4a N0 M0 T4a N1a M0 T1-4a N1b M0 T4a any N M0 From American Joint Committee on Cancer: AJCC Cancer Staging Manual. 6th ed. New York: Springer; AMES In the AMES system, patient age, the presence of metastases, extent of tumor invasion, and tumor size were used to stratify patients into low-risk and high-risk groups (Table 124-2). Low-risk patients were young (men, <41 years old; women, <51 years old) without distant metastases and all older patients without extrathyroidal papillary carcinoma, without major invasion of the tumor capsule by follicular carcinoma or with a primary tumor less than 5 cm in diameter. In a review of 310 patients from , low-risk patients (89%) had a mortality of 1.8% compared with a mortality rate of 46% in high-risk patients (11%). Recurrence in low-risk patients was 5%, and in high-risk patients was 55%. [53] In DAMES, nuclear DNA content was added to the AMES system to improve riskstratification for papillary thyroid carcinoma. [54] Table Factors Used in Prognostic Classification Systems TNM AMES AGES MACIS

5 TNM AMES AGES MACIS Patient Factors Age X X X X Gender X X Tumor Factors Size X X X X Histologic grade X Histologic type X X * * Extrathyroidal spread X X X X Lymph node metastasis X Distant metastasis X X X X Incomplete resection X * AGES/MACIS classifications for papillary carcinomas only. AGES and MACIS In the original AGES system, age at diagnosis, histologic tumor grade, extent of disease at presentation, and tumor size were used to calculate a prognostic score. [55] Because of the infrequent practice of tumor grading, a more recent modification of the system eliminated histologic tumor grade and incorporated metastasis and extent of resection. The MACIS system accounts for metastasis, age at diagnosis, completeness of surgical resection, extrathyroidal invasion, and tumor size. [56] The MACIS score is calculated as follows: Patients were stratified by their prognostic scores into four groups with statistically significant differences in 20-year disease-specific mortality. Other risk-classification systems with similar diagnostic criteria have been described. [57-59] Although numerous multivariable prognostic scoring systems have been developed, none is universally accepted. Additionally, none of these classifications has shown clear superiority, and application of these systems to a single population has shown incompatible findings compared with the original studies. [59,60] These systems do not apply to patients with poorly differentiated and more aggressive thyroid carcinomas. Nevertheless, some general conclusions can be drawn from these studies regarding the prognosis of patients with well-differentiated thyroid carcinomas. Low risk for tumor recurrence and diseasespecific mortality is noted in patients who are younger at diagnosis, have smaller primary tumors that lack extrathyroidal extension or regional/distant metastases, and have complete gross resection of disease at the initial surgery. Delay in treatment negatively affects prognosis. The most significant overall indicator of a poor prognosis is distant metastases, however, especially to bone. [6] Although a single risk-classification strategy is unavailable, these criteria should guide physicians to use therapeutic strategies that are directed toward the particular disease and risk for an individual patient, rather than applying a general treatment strategy for all patients with a particular form of thyroid carcinoma. More recent management guidelines from the American Thyroid Association (ATA) have recommended use of the AJCC/UICC staging system for all patients with differentiated thyroid cancer.

AGES and MACIS In the original AGES system, age at diagnosis, histologic tumor grade, extent of disease at presentation, and tumor size were used to calculate a prognostic score.

Recurrent & Persistent Papillary Thyroid Cancer Central Nodal Dissection vs. Node-Picking Patterns of Nodal Metastases Recurrent Laryngeal Nerve,

Recurrent & Persistent Papillary Thyroid Cancer Central Nodal Dissection vs. Node-Picking Patterns of Nodal Metastases Recurrent Laryngeal Nerve, Larynx, Trachea, & Esophageal Management Robert C. Wang,