Endocrinology and Metabolism Clinics of North America
Papillary Thyroid Cancer: Monitoring and Therapy
Section snippets
Initial presentation
Thyroid cancer is diagnosed in women two to three times more often than in men. Although it can present at any age, the median age at diagnosis is close to 45 years of age. Most patients present with an asymptomatic painless mass in the thyroid that is detected by the patient or their health care provider. Thyroid function tests are almost uniformly normal [10].
Although fine-needle aspiration has the highest sensitivity and specificity for identification of malignant thyroid nodules, several
Clinical guidelines
Over the last few years, several thyroid cancer specialist organizations around the world have published guidelines specifically addressing the pertinent management issues in thyroid cancer [11], [24], [25], [26], [27], [28]. In the following sections, we explore the similarities and differences in the recommendations provided in these various guidelines to determine where there is uniform agreement and where we continue to have areas of controversy. Because each of the guidelines includes an
Risk stratification
Risk stratification is the cornerstone of treatment and follow-up recommendations. Over the years, a relatively small group of clinical and histopathologic factors have been shown to be significant predictors of disease-specific mortality and usually risk of recurrence [29], [30]. These include patient factors such as age at diagnosis and gender and tumor-related factors such as size of the primary tumor, extent of extrathyroidal invasion, specific tumor histology, and distant metastases (Table
Goals of initial therapy
As outlined in the ATA guidelines [25], the goals of initial therapy are to surgically remove all evidence of gross disease in the neck while minimizing treatment and disease-related morbidity. In situations where radioactive iodine remnant ablation is required, complete surgical removal of the normal thyroid tissue facilitates the efficacy of RAI in destroying the remaining microscopic normal remnant and any metastatic disease that may be present. Furthermore, our initial therapies, if
Primary surgical considerations regarding extent of thyroid resection
Because of the high prevalence of metastatic cervical lymph node involvement in differentiated thyroid cancer, several of the guidelines recommend routine preoperative ultrasonographic evaluation of neck lymph nodes to properly plan surgical intervention [11], [25], [26]. Preoperative ultrasound (US) identifies suspicious cervical adenopathy in 20% to 30% of cases and in some cases alters the planned surgical approach [38], [39]. Because US is used in nearly all patients as routine follow-up in
Primary surgical considerations regarding extent of lymph node resection
Compartment-oriented lymph node dissections are recommended in all the guidelines for patients who have known lymph node metastases detected on preoperative staging or intraoperatively. The guidelines uniformly agree that functional neck dissection is preferred over “berry picking” and that radical neck dissection is rarely indicated. All the guidelines note that this approach decreases the risk of recurrence in low-risk patients and may prolong survival in high-risk patients.
The BTA and the
Radioactive iodine remnant ablation
The use of radioactive iodine in the postthyroidectomy setting to destroy residual thyroid bed tissue has become known as radioactive iodine remnant ablation (RRA). Because RRA has been shown in selected patients to decrease recurrence rates [22], [42], [43], [44], [45], [46] and decrease disease-specific mortality [22], [42], [44], [45], [46], it must also have a tumoricidal effect beyond destroying the microscopic residual thyroid cells remaining after a total thyroidectomy. Often, this
Details of radioactive iodine remnant ablation
Most of the guidelines recommended a low iodine before RRA, but the duration varied from 1 to 4 weeks (Table 7). The ATA and ETA noted that thyroid hormone withdrawal or recombinant human TSH (rhTSH) stimulation was acceptable for routine RRA [25], [26], whereas the NCCN, BTA, and AACE did not discuss the possible use of rhTSH as preparation for remnant ablation [11], [24], [27].
With regard to diagnostic whole-body scanning before ablation, there was general concern for stunning with higher
Role for external beam irradiation in initial therapy
In the setting of initial therapy, external beam radiation is seldom necessary in patients who have papillary thyroid cancer [52]. The guidelines are in agreement that external beam radiation therapy (EBRT) is most often used for unresectable tumors that do not concentrate RAI or for older patients (>45 years) who have evidence of gross extrathyroidal extension of the tumor into surrounding structures that are likely to have microscopic or small-volume macroscopic disease that is not amenable
Role of thyroid-stimulating hormone suppressive therapy
Suppression of TSH with supraphysiologic doses of levothyroxine to decrease the rate of progression and recurrence of thyroid cancer has been a cornerstone of treatment for more than 40 years [53], [54]. Retrospective studies suggest that TSH suppression to less than 0.1 mU/L may be beneficial in high-risk patients [55], [56], but the benefit of aggressive TSH suppression is much less clear in low-risk patients. Although all would agree that it is wise to avoid prolonged elevations in TSH, the
Serum thyroglobulin
As newer assays with improving sensitivities have become commercially available over the last 10 to 20 years, serum Tg determination has become the primary marker of differentiated thyroid cancer [57]. Although Tg is an excellent marker for well differentiated thyroid cancer, poorly differentiated tumors can produce Tg poorly and can evidence clinically significant recurrent disease with minimal Tg elevations [58]. Not all thyroid cancer recurrences that are detected with high-resolution US,
Follow-up strategy for detecting persistent/recurrent disease
Follow-up paradigms for detecting recurrent disease are usually based on whether the patient is considered high risk or low risk for death from disease. Although these approaches are useful, it may be more instructive to base the follow-up strategy on an understanding of the biology of the tumor and likely sites of recurrence. For example, a 25-year-old woman with a 3-cm papillary thyroid cancer involving several lymph nodes at diagnosis is likely to have a well differentiated tumor that should
Treatment options for persistent/recurrent disease
In the setting of clinically recurrent thyroid cancer, each of the guidelines endorses consideration of additional surgery if lesions are resectable and consideration of additional RAI if the lesions are likely to be RAI avid. Likewise, each guideline agrees that EBRT is usually only considered if the recurrent disease is not surgically resectable and is likely to be unresponsive to RAI. Therefore, initial investigations searching for persistent/recurrent disease should focus on neck US and
Treatment options for distant metastases
Although distant metastases are present in only 3% to 5% of patients who have papillary thyroid cancer at diagnosis, they can become evident in as many as 9% to 10% of patients who have papillary thyroid cancer and in as many as 20% of patients who have follicular thyroid cancer during the course of follow-up. In young patients, the pulmonary metastases often present as small, military, diffuse lesions throughout both lungs that usually respond well to repeated doses of RAI [69]. RAI is much
Summary
The last 10 years have seen a number of major paradigm shifts in the management of thyroid cancer. This is largely secondary to the more widespread use of highly sensitive detection tools, such as neck ultrasonography, highly sensitive Tg assays, and 18 FDG PET scanning in routine clinical practice. In addition, the ability to offer RAI studies, radioactive iodine remnant ablation, and stimulated Tg measurements with rhTSH rather than traditional thyroid hormone withdrawal has allowed many
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