Prophylactic Central Lymph Node Dissection: Continued Controversy

Low-risk papillary thyroid carcinoma (PTC), by definition, requires careful balancing of the risks of treatment and the risks of the disease. As Dr. Mazzaferri has noted, the critical factors in surgical decision-making are the extent of thyroidectomy and the extent of lymph node dissection. The long-running controversy regarding total vs less-than-total thyroidectomy for clinically significant thyroid cancer is now generally accepted to be resolved in favor of total thyroidectomy, based on the data from Bilimoria et al as detailed by Dr. Mazzaferri.[1] For any patients with a significant risk of persistent disease, total thyroidectomy improves disease-specific and recurrence-free survival, presumably as it forms part of an overall management strategy that includes radioiodine remnant ablation and thyroid-stimulating hormone suppression.

Lymph Node Management

Recommendations for the management of lymph nodes in PTC have been confounded by the overall good prognosis of thyroid cancer and the difficulty that creates for performing prospective trials. It has traditionally been accepted that regional lymph node metastases in PTC may increase regional recurrence rates but do not ultimately affect survival, as attested by the omission of regional lymph node metastases in the AMES, AGES, and MACIS prognostic scoring systems. However, this view has been challenged by data, including a large population-based study demonstrating increased mortality associated with regional lymph node metastases.[2] Hence, there has been a recent focus on the role of operative management of cervical lymph node metastases during the initial operation for thyroid cancer.[3]

There is universal agreement that lymph node involvement should always be assessed by preoperative examination and ultrasound, and by intraoperative inspection, and that evidence of central compartment node (level VI) involvement should prompt therapeutic complete dissection of the nodes in that compartment, rather than “berry-picking.” It is also accepted that prophylactic dissection of the lateral neck compartments (levels I–V) is not necessary, as those compartments of the neck are not violated during thyroidectomy and so could be dissected at a later time without increased risk due to the reoperative field.

Prophylactic Central Lymph Node Dissection

The area of significant controversy is the utility of prophylactic central lymph node dissection. Prophylactic dissection denotes removal of lymph nodes that appear normal by palpation and imaging studies preoperatively and intraoperatively. In contrast, therapeutic dissection denotes removal of lymph nodes that likely contain metastatic disease based on palpation or imaging studies. The evidence for this has been catalogued previously.[4]

The arguments for prophylactic central neck dissection are as follows:

• Lymph node metastases have a negative effect on patient outcome
• Lymph node metastases in the central neck cannot be reliably identified at operation
• Meticulous central neck node dissection has a beneficial effect on subsequent course
• Central neck dissection can be performed safely
• Reoperation for central neck recurrence has increased morbidity

One strategy to avoid prophylactic dissection is to actively evaluate the central compartment for metastasis, and perform therapeutic dissection if the nodes are involved. However, the central compartment nodes cannot be sensitively assessed by either preoperative ultrasound examination[5,6] or by intraoperative examination.[6] Without the capability to reliably identify node metastasis at ultrasound or operation, this assessment strategy cannot replace prophylactic dissection. However, actively seeking node involvement to guide the extent of operation is preferable if prophylactic dissection is not chosen routinely.

No prospective, randomized data exist to explain the impact of central lymph node dissection on recurrence or disease-specific mortality in PTC. One prospective Swedish study with contemporaneous controls provides the best available data to support an improvement in survival. Four retrospective cohort studies also exist, with mixed results: two support improvement by node dissection and two show no difference. One retrospective cohort study provides related evidence using thyroglobulin levels as a surrogate endpoint. On balance, there is some evidence to support improvement in outcome by including dissection, and only underpowered studies that show no difference.[4]

Operative Morbidity

One concern regarding the use of routine prophylactic central neck dissection in thyroid cancer treatment is operative morbidity. Total thyroidectomy without lymph node dissection, performed by surgeons experienced in the procedure, results in permanent hypoparathyroidism in 1% to 2% of patients and permanent nerve injury (recurrent laryngeal, external branch of the superior laryngeal) in 1% to 2% of patients. No high-level evidence exists to define whether the addition of central lymph node dissection to total thyroidectomy for PTC confers an increased risk of permanent hypoparathyroidism or permanent nerve injury. In expert series with liberal use of parathyroid autotransplantation, there does not appear to be any increased morbidity; however, other studies are mixed in their information regarding increased permanent hypoparathyroidism.[4] The morbidity appears likely related to surgical skill and experience, but it is clear that central node dissection can be performed safely by selected surgeons.

Conclusions

As Dr. Mazzaferri has so nicely detailed, there are significant continuing controversies in the management of low-risk papillary thyroid cancer. The surgical controversy regarding the extent of thyroid dissection is now largely resolved. However, the application of prophylactic central neck dissection to patients with differentiated thyroid cancer remains controversial. As for many issues regarding the management of differentiated thyroid cancer, there are no level 1 data to support or refute the hypothesis that central neck dissection at the time of initial thyroid cancer treatment is beneficial. However, in expert surgical hands, the addition of central neck node dissection to total thyroidectomy should carry no increased patient risk, and likely has benefit for disease-free and possibly overall survival in patients who are at some risk of recurrence. Finally, the value of identifying those patients who are definitively node negative is not yet clear, but dissection may also benefit them by defining a group who can receive limited or no adjuvant therapy, and who may require less intensive follow-up.

Financial Disclosure:The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References:

1. Bilimoria KY, Bentrem DJ, Ko CY, et al: Extent of surgery affects survival for papillary thyroid cancer. Ann Surg 246:375-384, 2007.
2. Lundgren CI, Hall P, Dickman PW, et al: Clinically significant prognostic factors for differentiated thyroid carcinoma: A population-based, nested case-control study. Cancer 106:524-531, 2006.
3. Cooper DS, Doherty GM, Haugen BR, et al: Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 16:109-142, 2006.
4. White ML, Gauger PG, Doherty GM: Central lymph node dissection in differentiated thyroid cancer. World J Surg 31:895-904, 2007.
5. Ito Y, Tomoda C, Uruno T, et al: Clinical significance of metastasis to the central compartment from papillary microcarcinoma of the thyroid. World J Surg 30:91-99, 2006.
6. Kouvaraki MA, Shapiro SE, Fornage BD, et al: Role of preoperative ultrasonography in the surgical management of patients with thyroid cancer. Surgery 134:946-955, 2003.