Initial Thyroid Surgery
The natural history of papillary thyroid cancer is such that patients who achieve disease-free status after total thyroidectomy and 131I therapy usually reach normal life expectancy.[14] Yet despite slow tumor growth and favorable prognosis for survival with small papillary thyroid cancers, the most challenging problem is controlling locoregional recurrences.[15] Whether this is best accomplished with surgery or 131I—or whether patients with small papillary cancers should be treated at all—has been the substance of ongoing debate, especially concerning patients with tumors smaller than 2 cm.[3,6] The optimal extent of surgery has been debated for decades, with some opting for total thyroidectomy[15] and others for lobectomy or subtotal thyroidectomy,[16] particularly for younger patients with small tumors. This is a critical decision. The extent of initial surgery for papillary thyroid cancer sets the stage for subsequent adjunctive therapy.
What is the optimal extent of initial thyroid surgery?
Cumulative Thyroid Cancer Recurrence Rates
The debates concerning the extent of thyroid surgery have been largely silenced by a recent study of the AJCC National Cancer Data Base by Bilimoria et al,[17] including 52,173 patients with papillary thyroid cancer who were surgically treated from 1985 through 1988.[17] The operations were classified as either total thyroidectomy (bilateral resection) or lobectomy (unilateral resection). In all, 43,277 patients (83%) had total thyroidectomy and 8,946 (17%) had lobectomy. The tumors were smaller than 1 cm in 24%, 1 to 2 cm in 30%, and larger than 2 cm in 46% of the patients. At the time of diagnosis, metastases were found in lymph nodes in almost 35% of the patients, and 2% had distant metastases. Unfortunately, information concerning 131I therapy was missing in approximately two-thirds of the patients.
Recurrence rates were almost 6% at 5 years and 9% at 10 years, increasing significantly by 1 cm tumor increments (P < .001, Figure 2). The 10-year cancer-specific survival rates declined with increasing tumor size; however, survival was statistically worse only for patients with tumors larger than 4 cm (P < .0001, Figure 3). Multivariate analysis found that lobectomy was associated with a 57% higher risk of recurrence (P = .001) and a 21% higher risk of cancer death (P = .027) compared with total thyroidectomy.
Cumulative Thyroid Cancer Mortality Rates
To determine the threshold size that affected outcomes, tumor size was stratified by 1-cm increments up to 4 cm for the Cox analysis. For patients with tumor size less than 1 cm, there was no difference in recurrence or survival between total thyroidectomy and lobectomy. However, for patients with tumors 1 cm or larger, lobectomy was associated with a 15% higher risk of recurrence (P = .04) and a 31% higher rate of cancer death (P = .04), as compared with that of total or near-total thyroidectomy. To evaluate the possibility of a confounding effect of larger tumors upon the analysis, patients with tumors 1 to 2 cm in size were examined separately. In this group, patients who underwent lobectomy had a 24% higher risk of recurrence (P = .04) and a 49% higher risk of 10-year cancer mortality compared with those who had a total thyroidectomy (P = .04).
ATA recommendation R26[9] is that the surgical procedure for patients with thyroid cancer larger than 1 cm should be a near-total or total thyroidectomy unless there are contraindications to this surgery (near-total thyroidectomy is removal of all thyroid tissue, leaving amounts of thyroid tissue < 1 cm to spare the recurrent laryngeal nerves and parathyroid glands). The guideline further suggests that thyroid lobectomy alone may be sufficient treatment for small (< 1 cm), low-risk, unifocal, intrathyroidal papillary carcinomas in the absence of prior head and neck irradiation or radiologically or clinically involved cervical nodal metastases. The ATA classifies that as an “A” recommendation (ie, their guidelines task force “strongly recommends” it).[9]
Initial Surgery for Cervical Lymph Node Metastases
Cervical Lymph Node Compartments
Ongoing controversy surrounds the optimal initial management of papillary lymph node metastases.[18,19] The neck is divided into seven contiguous lymph node compartments that are identified by roman numerals I to VII (Figure 4). Compartment VI creates the greatest concern for surgical complications and unsuspected lymph node metastases, which are found in 50% to 65% of patients.[20,21] Still, lymph node metastases occur nearly as often in the ipsilateral lateral cervical compartment levels III and IV, with fewer metastases in level II, while a small number skip past the usual path of metastasis and are found in contralateral compartments III and IV.[22]
Lymph node metastases are most common at the extremes of age. They are found in 25% to 60% of both low- and high-risk patients, depending on the extent of the compartment dissection.[23,24] Children with papillary thyroid cancer present with even more extensive lymph-node metastases, ranging from 50% to 90% at the time of diagnosis.[25-28] Children nonetheless have a relatively favorable outcome after initial therapy, with disease-free survival rates of 80% at 5 years and 60% at 10 years, providing they are adequately treated with total thyroidectomy and 131I ablation.[25,26,29] Children and adolescents have a good prognosis with prolonged survival, even when extensive regional disease or lung metastases are present at the time of diagnosis, but very long-term follow-up is needed to appreciate the impact of the disease in children.[30,31] It is best to think of outcome in young patients in terms of normal life expectancy, which casts a different light on survival and recurrence rates.
It has been widely held that lymph node metastases from papillary thyroid cancer increased local recurrence rates without affecting survival; however, newer studies suggest otherwise. A study of almost 10,000 patients found 14-year all-cause survival rates of 79% and 82% in patients with and without lymph-node metastases, respectively (P < .05).[32]
Another study[33] of 33,088 patients with papillary cancer lymph node metastases found a 46% increased risk of cancer-specific death in patients age 45 years or older compared with patients who did not have lymph node metastases (P < .001).[33]
Metastatic lymph nodes that remain after initial therapy are the most common cause of recurrence.[23,24] Moreover, the larger the number of cervical lymph node metastases, the more serious the long-term outcome in terms of tumor recurrence and distant metastases.[34] This occurs in both children and adults with papillary thyroid cancer, and in adults with papillary microcarcinomas < 1 cm.[8,20,23,35]
| After total thyroidectomy: | |
| • | No further therapy other than levothyroxine |
| • | Maintain TSH < 0.1 mU/L indefinitely |
| • | Radioiodine therapy with 30 mCi |
| • | Radioiodine therapy with 100 mCi |
The treatment of lymph node metastases rests on a fine balance of the risks and benefits of both lymph node surgery and the use of postoperative 131I. The ATA guidelines[9] suggest systematic lymph node dissection, which refers to an en bloc dissection of anatomic node compartments, as opposed to selectively excising lymph-nodes, often referred to as “berry-picking,” which is not recommended. Therapeutic lymph-node dissection is removal of malignant lymph nodes identified before or at the time of surgery, whereas prophylactic dissection refers to excision of lymph nodes that are considered normal preoperatively and at the time of surgery.
ATA recommendation R27[9] suggests that therapeutic central-compartment (level VI) or lateral neck compartment dissections should accompany total thyroidectomy to provide clearance of disease from the central neck (B recommendation, “based on fair evidence”).[9] Recommendation R27a suggests that prophylactic central-compartment neck dissection (ipsilateral or bilateral) may be performed in patients with papillary cancer with clinically uninvolved central neck lymph nodes, especially for advanced primary tumors (T3 or T4), which is a category C recommendation (“expert opinion”); and recommendation 27c suggests that near-total or total thyroidectomy without prophylactic central neck dissection may be appropriate for small (T1 or T2) noninvasive clinically node-negative papillary thyroid cancers (C recommendation).[9]
Yet the verification of this recommendation lies in identifying lymph node metastases preoperatively or at the time of surgery. The ATA guidelines suggest preoperative cervical ultrasonography in all patients undergoing thyroidectomy. Although this identifies suspicious cervical lymph nodes in up to half the cases,[36,37] altering the surgical approach in many patients, neck ultrasonography has important limitations. It may fail to identify extracapsular lymph node invasion deep in the neck and small lymph node metastasis within the central compartment (VI), which may lower the sensitivity of ultrasonography to 35% or more.[38,39]
| • | Total thyroidectomy with prophylactic level VI lymph node dissection done by a very experienced surgeon is the optimal means of surgically removing all tumors in the neck, but can result in hypoparathyroidism or unintended laryngeal nerve damage. |
| • | Radioiodine (131I) therapy is the optimal means of destroying residual microscopic thyroid cancer, but is associated with damage to non-thyroidal tissues and carries a small risk for causing nonthyroidal cancers and leukemia. |
| • | Following thyroid surgery that leaves no evidence of residual tumor, small amounts of 131I (~30 mCi) and preparation with recombinant human TSH significantly reduces total-body irradiation and permits follow-up with thyroglobulin to accurately identify occult tumor. |
| • | Patients can be reliably assured to be free of disease when all of the following are present: no clinical and ultrasound evidence of tumor, and undetectable serum thyroglobulin during both TSH suppression and stimulation without antithyroglobulin antibodies. TSH can be maintained in the low normal range by thyroid hormone when the patient is free of disease |
White et al[19] conducted a systematic review using evidence-based criteria and found no prospective randomized studies to explain the impact on outcome of central lymph node dissection in patients with papillary thyroid cancer. The authors concluded that systematic compartment-oriented central lymph node dissection may decrease recurrence of papillary cancer and likely improves disease-specific survival (C recommendation). They also noted that adding central (level VI) lymph node dissection to total thyroidectomy can significantly reduce serum thyroglobulin (Tg) levels.[19] They found a higher than usual rate of permanent laryngeal nerve injury and hypoparathyroidism with compartment-oriented central lymph node dissection. This must be weighed against the fact that reoperation in the central neck compartment for recurrent papillary cancer substantially increases the risk of hypoparathyroidism and unintentional laryngeal nerve injury compared with total thyroidectomy with or without central lymph node dissection (C recommendation). This finding alone may support a more aggressive initial operation in the central neck.[19]
Until recently, only one strong study supported prophylactic compartment dissection. In this trial, 160 patients with papillary cancer had systematic (prophylactic) compartment-oriented dissection of lymph node metastases, which improved recurrence (P < .0001) and survival (P < .005) rates, especially for patients with T1 to T3 tumors.[40]
A very recent study from Paris by Bonnet et al[39] provides important new information on systematic (prophylactic) lymph node metastases. In this retrospective study of 115 consecutive patients ranging in age from 17 to 73 years (mean, 48.5), all had papillary cancers smaller than 2 cm, ranging from 1 to 19 mm (mean, 12.5). Patients were selected for study on the basis of tumor size and a negative preoperative neck ultrasound examination (preoperative T1, ,N0, M0, stage I). All underwent total thyroidectomy and bilateral prophylactic dissections of the central neck (level VI) and ipsilateral lateral neck (levels III and IV). Further lateral neck dissection was based on the results of frozen section analysis of metastatic involvement of ipsilateral lateral levels III and IV.
The main finding of the study was that 42% of the patients had lymph node metastases, 45% of which were in the central compartment and 57% involving the lateral compartment. Almost 40% of the tumors would have been missed if the surgery had involved only the central neck. In 29% of the patients, tumors extended beyond the thyroid capsule. The final surgery was extensive: all 115 patients had bilateral level VI dissections, 96 (94%) had ipsilateral systematic level III to IV dissections (which were bilateral in 6%), and 11% had ipsilateral level II, III, IV and V dissections because tumor was in the superior thyroidal pole. Only one patient had permanent unilateral vocal cord paralysis (0.9%), and another had permanent hypoparathyroidism (0.9%).
In this study, prophylactic lymph node dissection had an important impact on selective remnant ablation. Radioiodine was not administered in 42% of patients with tumors less than 20 mm in diameter without metastatic lymph nodes, and 58% of the patients were treated with 131I as a result of lymph node metastasis, extracapsular thyroid invasion, or unfavorable histologic subtype. At the 1-year follow-up, all of the patients had negative neck ultrasound examinations and 97% had an undetectable serum Tg during either TSH suppression or recombinant human thyrotropin-α (Thyrogen [rhTSH]) stimulation, indicating there was no evidence of residual tumor. Only one patient had persistent foci of 131I uptake after therapy.
