Impact of Combined Prophylactic Unilateral Central Neck Dissection and Hemithyroidectomy in Patients with Papillary Thyroid Microcarcinoma

Sang Min Hyun, MD; Hyoung Young Song, MD; Sang Yoon Kim, MD; Soon Yuhl Nam, MD; Jong-Lyel Roh, MD; Myung Woul Han, MD; Seung-Ho Choi, MD

Department of Otolaryngology, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea

Abstract

Background. Lymph node metastases occur frequently in patients with papillary thyroid carcinoma (PTC), and the central compartment of the neck is the most frequently involved site. Some authors advocate prophylactic central neck dissection (CND) during initial thyroidectomy. However, little is known about the effects of prophylactic unilateral CND in papillary thyroid microcarcinoma (PTMC) patients who undergo hemithyroidectomy. This study was designed to investigate the impact of prophylactic unilateral CND in this patient population.

Methods. The clinical records of 152 patients with a PTMC ≤1 cm according to postoperative ultrasonography who underwent hemithyroidectomy between 2002 and 2009 were assessed retrospectively. Outcomes were compared between 65 (43%) patients who underwent hemithyroidectomy plus elective unilateral CND (CND+) and the 87 (57%) patients who underwent hemithyroidectomy only (CND– group).

Results. In the CND– group, 37 patients (43%) had locoregional recurrences, compared with 13 patients (20%) in the CND+ group. In high-risk PTMC patients (tumor size ≥6 mm and ETEs or extrathyroidal extension), CND was associated with a significantly lower rate of locoregional recurrence (p = 0.017).

Conclusions. Compared with hemithyroidectomy alone, prophylactic unilateral CND may reduce the rate of locoregional recurrence in patients with PTMC.

© Society of Surgical Oncology 2011
First Received: 11 December 2010
Published Online: 12 August 2011
S.-H. Choi, MD (email: shchoi@amc.seoul.kr)

Papillary thyroid carcinoma (PTC) is the most common histological type of thyroid malignancy. In most patients, PTC is characterized by an indolent course, and the overall 10-year survival rate exceeds 90%. During the past decade, an increase in the use of ultrasonography has led to an increase in the detection of papillary thyroid microcarcinoma (PTMC) ≤1 cm in size in the absence of nodal metastasis or other symptoms. Lymph node metastases are observed in 20–50% of patients with PTC, and the central compartment of the neck is the most frequently involved site. Because these metastases are difficult to detect using ultrasonography, some authors advocate routine central neck dissection (CND) in PTMC patients at the time of initial thyroidectomy, and many studies have reported that CND is not associated with increased morbidity. Central neck dissection may protect recurrence without influencing prognosis.

With increasing detection of PTC, minimal surgical procedures must be considered preferable to radical surgery. Moreover, the 2009 guidelines of the American Thyroid Association state that thyroid lobectomy is sufficient treatment for patients with small (<1 cm), unifocal, intrathyroidal, and clinically node-negative papillary carcinomas, whereas near-total or total thyroidectomy is appropriate treatment for patients with multifocal disease, extrathyroidal extension, or nodal metastasis. Thus, hemithyroidectomy is frequently performed for PTMC patients without CND. In such cases, prophylactic unilateral CND (ipsilateral to the involved lobe) may not be performed routinely, but may be indicated for selected PTMC cases in whom CND is considered beneficial. Unilateral CND may be performed in PTMC patients with high-risk features such as tumor size ≥6 mm or extrathyroidal extension (ETE) but without contralateral lobe involvement (T3 or T4). One benefit of unilateral CND is that it may provide accurate pathological information concerning lymph node status and thus the precise extent of locoregional lymph node metastasis and the prognosis. Prophylactic unilateral CND may improve disease control and provide important information concerning the tumor stage. This retrospective study was designed to assess the possible advantages of prophylactic unilateral CND in PTMC patients who undergo hemithyroidectomy in terms of the excision of occult metastases and a reduction in the rate of locoregional recurrence.

Materials and Methods

Between January 2002 and December 2009, 163 patients (133 female, 30 male) underwent hemithyroidectomy for PTMC at our institution. Surgery was performed by one of five head and neck surgeons. PTMC was defined as a PTC ≤1 cm in size according to postoperative ultrasonography.

Patients were excluded due to a discrepancy of more than 3 mm in tumor size between the preoperative ultrasonography and postoperative pathology measurements, bilateral lesions, recurrence after previous surgery, extrathyroidal extension (ETE), lymph node, or distant metastases diagnosed preoperatively, or associated with other diseases. A diagnosis of PTMC was established by pathologists after surgery, referring to current histological classifications. High risk patients confirmed to have bilateral lesions or ETE, or pathologically proven nodal metastasis underwent total thyroidectomy and central CND.

Unilateral CND was performed by removing all lymph nodes between the carotid sheaths and the trachea laterally, the hyoid bone superiorly, the suprasternal notch inferiorly, and the esophagus posteriorly. All surgical specimens were fixed in buffered formalin, embedded in paraffin, sectioned, and stained with hematoxylin and eosin. Clinicopathological data such as sex, age, tumor size, extrathyroidal extension, pathologic multicentricity, recurrence, and type of surgery were retrospectively collected.

Patients were grouped into those who underwent hemithyroidectomy alone (CND– group) and those who underwent hemithyroidectomy with prophylactic unilateral CND (CND+ group). The primary outcome was locoregional recurrence, defined as clinically confirmed or pathologically proven recurrence after thyroidectomy. Locoregional recurrence-free survival was calculated using the Kaplan–Meier method, and prognostic factors were analyzed by univariate and multivariate analysis. The following factors were considered: sex, age, tumor size, extrathyroidal extension (ETE), multicentricity, recurrence, and nodal metastasis.

Data were analyzed by using SPSS statistical software (Version 12.0 for Windows, Chicago). Categorical data were compared using two-tailed Fisher’s exact test. The Kaplan–Meier method was used to calculate locoregional recurrence-free survival, and differences were compared using the log-rank test. A multivariate analysis was performed by the Cox proportional hazards model.

Results

The clinical and demographic characteristics of the two groups are shown in Table 1. No significant differences were observed between the CND– and CND+ groups in terms of sex, mean age, tumor size, pathologically confirmed multicentricity, postoperative tumor size >1 cm, extrathyroidal extension, recurrence, or completion thyroidectomy (p > 0.05).

In the CND+ group, 19 patients (29%) had pathologically identified central lymph node metastasis. The mean follow-up period was 61.8 months (range, 24–96 months). During follow-up, locoregional recurrence occurred in 37 patients (43%) in the CND– group and 13 patients (20%) in the CND+ group (p = 0.003).

The 5-year locoregional recurrence-free survival rate was significantly higher in the CND+ group than in the CND– group (p = 0.017).

Of the 37 patients with recurrence in the CND– group, 20 patients with ETEs and extrathyroidal extension (47%) had significantly higher recurrence rates compared with the remaining 17 patients without ETEs (22%) (p = 0.025). Among the 13 patients with recurrence in the CND+ group, 9 had ETEs (75%) and 4 had no ETEs (p = 0.017).

Completion thyroidectomy was performed in 24 patients (28%) in the CND– group and 23 patients (35%) in the CND+ group (p = 0.375). Indications for surgery included completion thyroidectomy due to contralateral tumors, the need for lifelong thyroid hormone replacement—

Table 1. Clinical and demographic characteristics of the CND– and CND+ groups

ᵃ Size range: 2–12 mm; mean value, 5.84 ± 2.75 mm
ᵇ Two-tailed Fisher’s exact test

Table 2. Correlation between level VI metastasis and extrathyroidal extension or multifocality

ᵃ Two-tailed Fisher’s exact test

Table 3. Completion thyroidectomy in the CND– and CND+ groups

ᵃ Two-tailed Fisher’s exact test

ETE extrathyroidal extension; CND central neck dissection; pN pathological lymph node

therapy, and general anesthesia (Fig. 1). One of these 23 patients subsequently developed tumor recurrence (patient 8).

During follow-up, 14 patients (n = 1, CND+; and n = 13, CND–) developed tumor recurrence (Table 4). Six had contralateral lobe recurrence only (i.e., without nodal recurrence), and eight had nodal recurrence with unilateral central neck metastases. Of these eight patients, six developed recurrence in the central neck compartment only, and two developed recurrence that included ipsilateral level III and IV metastases with the central neck compartment (patients 7 and 8). Of the eight patients with nodal recurrence, three developed simultaneous recurrence in the contralateral lobe.

Univariate analysis showed that unilateral CND (p = 0.017) had a significant negative correlation with tumor recurrence. Multivariate analysis showed that unilateral CND (p = 0.045) was an independent predictor of locoregional recurrence (Table 5; Fig. 2).

Discussion

Although the optimal treatment for PTC has been the subject of considerable debate during the past two decades, hemithyroidectomy is now considered an adequate treatment for small (<1 cm), low-risk, unifocal, intrathyroidal papillary carcinomas in the absence of radiologically or clinically involved cervical nodal metastasis. However, in the present cohort, prophylactic unilateral CND combined with hemithyroidectomy decreased the locoregional—

Figure 1.

In the CND– group, 24 of 37 patients with ETEs underwent completion thyroidectomy; in the CND+ group, 23 of 33 patients with ETEs or nodal metastases underwent completion thyroidectomy. One patient who declined completion thyroidectomy subsequently developed tumor recurrence.

Table 4. Characteristics of patients with recurrence

ETE extrathyroidal extension; CND central neck dissection; pN pathological lymph node

Figure 2.

Kaplan–Meier analysis of locoregional control rates in 152 patients with small papillary thyroid carcinoma who underwent combined hemithyroidectomy and ipsilateral central neck dissection (CND+) or hemithyroidectomy alone (CND–).

p = 0.0174 (log-rank test)

(Graph shows disease-free survival rate vs. time in months, with CND+ group maintaining higher control rates than CND– group.)

Table 5. Univariate and multivariate analysis of factors that affect locoregional recurrence

ᵃ Kaplan–Meier survival analysis with log-rank test
ᵇ Proportional hazards Cox’s regression model
HR hazard ratio; CI confidence interval

As increasing numbers of patients with PTMC ≤1 cm without nodal metastasis are being identified by preoperative ultrasonography, in such patients, hemithyroidectomy has several advantages over total thyroidectomy. The major benefit of hemithyroidectomy is that the risk of recurrent laryngeal nerve and permanent damage to parathyroid glands and bilateral parathyroid impairment injury is substantially reduced, since overall complication frequency is only unilateral. Thus, the potential for permanent or temporary hypocalcemia may be decreased by not exploring the contralateral central neck compartment. In addition, hemithyroidectomy may reduce the need for lifelong thyroid hormone replacement compared with total thyroidectomy. However, the disadvantage of this procedure includes a higher risk of recurrence, the subsequent need for revision surgery, and the possible need for completion thyroidectomy.

The present findings suggest that prophylactic unilateral CND with hemithyroidectomy may increase the likelihood of detecting occult nodal metastases compared with hemithyroidectomy alone, and additional completion thyroidectomy would not affect locoregional control. In this study, 29% of the patients had metastases, and among the CND+ group of 65 patients, 20 (29%) were found to have occult central nodal metastases.

Several authors have previously reported that occult central nodal metastases may be present in PTMC patients in up to 40% of cases, supporting the present findings to a greater extent. Up to this point, an important question has been whether patients with occult nodal metastases benefit from prophylactic CND in terms of recurrence, survival, and complications.

Although the overall recurrence rate in the present cohort was not significantly different between the CND– and CND+ groups, subgroup analysis revealed that prophylactic unilateral CND may reduce the locoregional recurrence rate in high-risk PTMC patients and permanently improve locoregional control. Compared with total thyroidectomy, hemithyroidectomy combined with prophylactic unilateral CND may reduce the risk of hypocalcemia and recurrent laryngeal nerve injury by reducing the need for reoperation.

Statistical analysis revealed that completion thyroidectomy was not an independent factor influencing recurrence in the present cohort. Combined unilateral CND and adjuvant RAI therapy may have an important impact on local recurrence. However, only 5 patients in this study underwent operation completion thyroidectomy, 4 had ETEs or/and recurrence in contralateral thyroid lobes, which is a small sample size. The evaluation of larger samples is warranted to investigate this hypothesis further.

Unilateral CND was associated with a decrease in the local recurrence rate in the present cohort. Of the 14 patients who developed recurrence, 6 developed recurrence in the contralateral lobe only, although whether central neck metastases were present is unknown. These patients underwent completion thyroidectomy and RAI therapy without CND, and it is difficult to detect central neck metastases by means of ultrasonography. The locoregional recurrence rate was significantly higher in the CND– group compared with the CND+ group (p = 0.017).

Tumor recurrence was observed in 14 patients (9.2%), and the rate was higher than that reported by previous studies. Total thyroidectomy with CND may have been a better choice for the treatment of PTMC. However, some patients expressed concerns regarding the risk of bilateral vocal cord palsy and permanent hypocalcemia and were reluctant to commence lifelong thyroid hormone replacement therapy. For such patients, hemithyroidectomy with unilateral CND may represent an alternative surgical treatment.

Given the indolent course of PTMC, some of these cases may never recur. As a result, the recurrence rates generated here represent the hypothetical outcome that might have been. Alternatively, the low recurrence rate of recurrence was examined in this analysis because of the infrequency of performing completion thyroidectomy, because ultrasonography was performed only every 6–12 months during follow-up.

A high proportion of patients had features associated with poor prognosis: 40% had ETE or pN1a, and 6 patients were found to have contralateral lobe recurrence. Recurrence was detected mainly in the contralateral lobe, where occult metastases may have been undetected by ultrasonography. The sensitivity of ultrasonography in detecting micrometastases remains unsatisfactory, and CND could help reduce the risk of recurrence by eliminating occult metastases.

The limitations of this retrospective study are its non-randomized nature and controlled trial insufficiencies. A larger prospective and controlled trial including a larger patient base and longer follow-up period is warranted to validate the impact of CND on the locoregional control rate further.

In conclusion, prophylactic CND resulted in the excision of occult central lymph node metastases in approximately 30% of PTMC patients. Prophylactic unilateral CND and hemithyroidectomy may decrease the locoregional recurrence rate in this population.

Conflict of Interest

None.

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