This article outlines features of the biology of well differentiated thyroid cancer, and how these impact on systems of risk prediction. It covers salient points that the surgeon should consider from the clinical history and examination in the office, and outlines the procedures available for surgical management of thyroid cancer. The article then examines the choices that face thyroid surgeons both in relation to planning primary thyroid surgery and the approach to regional lymphadenectomy. In addition, key findings in the operating room are discussed in relation to their impact on decision making. Long-term outcomes are presented for patients following surgery.
Key points
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A surgical plan should be discussed preoperatively and based upon details of the clinical history, physical examination, and investigations.
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Patients with low-risk, intrathyroid disease should be offered thyroid lobectomy, while the remaining patients should be managed with total thyroidectomy.
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Patients with evidence of regional lymph node metastases should undergo systematic neck dissection, and patients considered without evidence of lymph node metastases (cN0) should not undergo elective lateral neck dissection.
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In the operating room, experience, clinical acumen, and frozen section should be used to adapt the surgical plan as required.
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With appropriate planning, low-risk patients will have survival rates greater than 95% at 10 years, and less than 50% of high-risk patients will die of disease.
Overview
Following preoperative investigation of thyroid cancer, which will involve ultrasound and cytologic assessment in most cases (as outlined elsewhere), the surgeon must decide upon an operative plan. This plan will be shaped by patient factors (such as age), ultrasonographic characteristics of the thyroid gland, thyroid nodules and associated regional lymph nodes, and the cytologic features of samples obtained (including presence of nuclear grooves and pseudoinclusions). Integration of these variables will allow the surgeon to assess the patient’s risk of recurrence and death from disease. An appreciation of this risk, in conjunction with an understanding of disease biology, will allow the surgeon to recommend the plan most likely to maximize chances of surgical cure and minimize the potential for morbidity with a single procedure.
The aim of this article is to provide an understanding of the biology of well differentiated thyroid cancer (WDTC), and how relevant features of the patient and tumor impact on clinical risk and outcome. The authors go on to outline the procedures available for managing WDTC and the rationale for selecting appropriate therapy on an individual risk-stratified basis for both in relation to the thyroid gland and regional lymph nodes. The article concludes with an overview of the long-term outcomes that patients with WDTC can expect.
Overview
Following preoperative investigation of thyroid cancer, which will involve ultrasound and cytologic assessment in most cases (as outlined elsewhere), the surgeon must decide upon an operative plan. This plan will be shaped by patient factors (such as age), ultrasonographic characteristics of the thyroid gland, thyroid nodules and associated regional lymph nodes, and the cytologic features of samples obtained (including presence of nuclear grooves and pseudoinclusions). Integration of these variables will allow the surgeon to assess the patient’s risk of recurrence and death from disease. An appreciation of this risk, in conjunction with an understanding of disease biology, will allow the surgeon to recommend the plan most likely to maximize chances of surgical cure and minimize the potential for morbidity with a single procedure.
The aim of this article is to provide an understanding of the biology of well differentiated thyroid cancer (WDTC), and how relevant features of the patient and tumor impact on clinical risk and outcome. The authors go on to outline the procedures available for managing WDTC and the rationale for selecting appropriate therapy on an individual risk-stratified basis for both in relation to the thyroid gland and regional lymph nodes. The article concludes with an overview of the long-term outcomes that patients with WDTC can expect.
Relevant anatomy and pathophysiology and their impact on risk prediction
WDTC is increasingly common, and papillary thyroid cancer is the most commonly encountered histologic subtype. Indeed, over 80% of thyroid cancers are now considered papillary. Interestingly, autopsy studies show high rates of clinically undetected disease in patients who die of other causes, a finding that suggests that many lesions never impact on patient outcome during life. Nonetheless, it is important to understand the pathology of this disease in order to make appropriate treatment decisions.
The increasing incidence of thyroid cancer is being driven in a large part by more intensive investigation of the US population. As such, the nature of the disease is changing. More patients with small-volume disease are presenting, and the average age at presentation is increasing. Today, the most commonly encountered thyroid cancer in the United States is a papillary carcinoma that measures less than 1 cm and has no detectable regional lymph node metastases.
Outcomes for patients with WDTC are excellent. Long-term follow-up of patients treated in many institutions confirms survival rates of over 90% at 10 years. The risk of recurrence and/or death can be estimated using a number of available systems based on patient and tumor factors. Prior to considering these, some points about the nature of the disease should be considered.
Papillary thyroid cancer (PTC) has a propensity both for multifocality and regional nodal metastasis. Approximately 40% of PTC cases are multifocal (more than 1 PTC present in the thyroid gland). Although this has little impact on oncological outcome, preoperative investigation may identify bilateral nodules, which may be addressed with a single surgery. Extrathyroid extension (ETE) is extremely uncommon in disease less than 1 cm, and more common in larger-volume primary tumors. Such ETE may be identified following clinical examination, on preoperative imaging, or on the operating table (gross ETE). This clinically apparent ETE has a significant impact, not only on rates of recurrence, but also on survival. In patients considered free of ETE following surgery, who have microscopic ETE on histopathological analysis, the impact is far less significant. Such patients are at higher risk of recurrence, but survival is unaffected by this finding.
In terms of regional disease, PTC metastasizes often and early. Even in those without clinical evidence of regional disease, occult metastases will be demonstrated in around 40% of patients if elective central and lateral neck surgery is performed. These occult nodes do not confer worse survival, particularly in younger patients, and in most patients will never manifest clinically during follow-up. The prognosis in patients with evident regional metastases at presentation is influenced by age. In younger patients, regional metastases do not place patients at higher risk of disease-specific death. This young patient group has a higher rate of subsequent regional failure, but such recurrences can be detected early and cured with appropriate surgery. In contrast, older patients with regional disease at presentation are at a higher risk of death. These patients have higher rates of distant recurrence, which impacts on survival.
Distant metastases are uncommon. In older patients, distant disease portends a grave prognosis. These patients cannot be cured surgically, and at advanced age, the response to radioactive iodine is limited, rendering the outcomes of treatment of systemic disease poor. In contrast, younger patients, particularly children, commonly present with pulmonary metastases. These young patients with extremely well differentiated cancers have iodine avid disease, which allows for excellent outcomes following adjuvant radioactive iodine (RAI) even in the presence of distant metastases.
Following preoperative assessment, patients can be stratified into low-, intermediate- or high-risk groups based on host and tumor characteristics. Low-risk patients are young (<45 years) with low-risk tumors (pT1/2 N0 M0). High-risk cases are older (>45 years) with high-risk tumors (T3/4 or M1). The remaining young patients with high-risk disease and older patients with low-risk disease constitute an intermediate-risk group ( Table 1 ). Such an approach allows patients to be stratified for treatment based on risk versus benefit assessment. More recently, recurrence risk stratification systems have been developed that include variables such as the presence of nodal disease and the degree of ETE ( Table 2 ).
| Risk Level | Patient Factor | Tumor Factor | |||
|---|---|---|---|---|---|
| Low risk | Age <45 y | Papillary Ca | M 0 | No ETE | Size <4 cm |
| High risk | Age >45 y | Follicular Ca/Hurthle Cell Ca | M1 | ETE | Size >4 cm |
| Low-risk case | Low-risk patient | Low-risk tumor | |||
| Intermediate-risk case | Low-risk patient | High-risk tumor | |||
| High-risk patient | Low-risk tumor | ||||
| High-risk case | High-risk patient | High-risk tumor | |||
| Regional Metastases | Distant Metastases | Extrathyroid Extension | Surgical Resection | Aggressive Pathology | RAI Uptake Outside Thyroid Bed | |
|---|---|---|---|---|---|---|
| Low risk: Only if all the following are true | Absent | Absent | Absent | Complete | Absent | Absent |
| Intermediate risk or High risk: In any of the following are true | Present | Absent | Microscopic | Complete | Present | Present |
| Present | Macroscopic | Incomplete |
Clinical presentation/examination
Most patients who present for thyroid surgery will have no signs or symptoms. However, this does not render clinical history and examination without clinical utility. The surgeon should elicit relevant features from the patient such as family history and exposure to ionizing radiation. The presence of high-risk features such as prior external beam radiation to the head and neck places the thyroid gland at higher risk of malignant change, and strengthens the case for total thyroidectomy. More significant symptoms such as voice change, dysphagia and hemoptysis suggest advanced disease.
Physical examination should include assessment of the general state of the patient, examination of the central neck and regional nodes, and assessment of vocal cord mobility in all patients. In those patients with a suspicion of fixation of the primary tumor, nodal metastases or vocal cord palsy, cross-sectional imaging of the head and neck, including the mediastinum, allows for an accurate assessment of disease extent.
In those patients considered to have invasive disease affecting the airway or esophagus, preoperative endoscopic assessment is essential to confirm the extent of disease and plan surgical therapy.
Available procedures and choice of procedure
Procedures such as nodulectomy and subtotal thyroidectomy no longer have a role in the management of WDTC. The minimum procedure that should be considered is extracapsular thyroid lobectomy when unilateral surgery is performed, and total thyroidectomy when bilateral surgery is required. The only exception to this is isolated, uninodular isthmic lesions that can safely be managed in selected low-risk patients using thyroid isthmusectomy, thereby avoiding entry to the tracheoesophageal grooves and minimizing the morbidity of surgery.
When selecting an appropriate surgical procedure, the surgeon must consider 3 factors: the need for resection of lymph nodes, the need for bilateral surgery, and the anticipated need for postoperative radioactive iodine ( Fig. 1 ).
