Select Patients with Thyroid Cancer May Not Require Prophylactic Central Compartment Neck Dissection

Select patients with papillary thyroid carcinoma with clinically involved lateral neck nodes (cN1b disease) may not require prophylactic central compartment neck dissection (PCND), according to our retrospective study published recently in the Annals of Surgical Oncology. ⁽¹⁾

The current guidelines of the American Thyroid Association (ATA) ⁽²⁾ and the National Comprehensive Cancer Network (NCCN) ⁽³⁾ endorse PCND in patients with cN1b thyroid cancer. Given the limited evidence supporting these endorsements, we examined outcomes for 152 patients who underwent surgery for well-differentiated thyroid carcinoma at Memorial Sloan Kettering Cancer Center (MSK) from 1986 to 2015.

A total of 103 patients (68 percent) did not have a PCND, and only two patients in this cohort developed a central neck recurrence by final follow-up. The five- and ten-year central neck recurrence-free probability was 98.4 percent in the non-PCND group and 93.6 percent in the PCND group (p = 0.133), with a median follow-up of 65 months. ⁽¹⁾

Despite the low morbidity associated with PCND, oncological benefit determines the extent of the initial surgery for papillary thyroid cancer at MSK. Our expert surgeons rely on physical examination, preoperative imaging, and intraoperative evaluation of frozen sections of suspicious nodes to determine whether a patient should have a PCND. For example, patients with bulky lateral nodal disease involving multiple or large metastatic lymph nodes are more likely to benefit from the intervention.

Thyroid Cancer and Current Surgical Guidelines

Overall, papillary thyroid cancer is associated with excellent survival outcomes. Regional lymph node metastases are common, occurring in about 30 to 80 percent of cases. ^{(4), (5), (6), (7)} Patients with clinically involved lateral compartment lymph node metastases often also have central compartment lymph node metastases. ^{(8), (9), (10)} The estimated risk of recurrence ranges from one to 40 percent. ⁽²⁾

Since the rate of pathological nodal metastases does not correlate with the rate of regional nodal recurrence, a proportion of nodal metastases must remain clinically insignificant, suggesting that neither PCND nor a prophylactic lateral neck dissection is required for all patients with papillary thyroid cancer. ⁽¹⁾

Further, adjuvant radioactive iodine therapy is usually administered in patients with cN1b disease, in accordance with ATA guidelines, ⁽²⁾ which may reduce the risk of central compartment recurrence and further limit the usefulness of PCND in select patients.

Current surgical guidelines endorse the role of PCND in patients with papillary thyroid carcinoma and clinically involved lateral neck nodes. The 2015 ATA guidelines recommend considering PCND for select patients with advanced primary tumors or clinically involved lateral neck nodes (cN1b). ⁽²⁾ The 2019 NCCN guidelines state that a central compartment neck dissection is required ipsilateral to a modified radical neck dissection performed for clinically involved lateral neck lymph nodes, in most cases. ⁽³⁾

However minimal, surgery of the central compartment carries the risk of injury to the parathyroid glands and recurrent laryngeal nerves, which can result in temporary or permanent hypoparathyroidism and hoarseness.

Study Design

For our study, we examined our institutional database of 6,259 patients who underwent initial surgery for well-differentiated thyroid carcinoma from 1986 to 2015. We identified 152 patients with cN1b disease but no evidence of central compartment lymph node metastases on preoperative imaging and intraoperative evaluation. ⁽¹⁾

Preoperative imaging included ultrasound, computed tomography scan, or magnetic resonance imaging scan. Intraoperative evaluation involved an assessment of the central compartment based on the appearance and palpation of level 6 and 7 lymph nodes to determine the likelihood of malignancy. ⁽¹⁾

We evaluated the central neck recurrence-free probability and disease-specific survival outcomes for patients who had or had not received PCND.

Study Findings

The median age among the 152 patients was 49 years (range 19 to 79), and 57 percent were female. The majority (97 percent) of patients had a primary tumor less than 4 cm, and 47 percent had microscopic gross extrathyroidal extension. ⁽¹⁾ According to the ATA’s risk stratification, 72 percent had intermediate-risk, and 24 percent had high-risk cancer. ⁽²⁾ All patients were stage I or stage II, as classified according to the American Joint Committee of Cancer’s tumor node metastases staging system. ⁽¹¹⁾

Among the 152 patients, 103 patients (68 percent) had not received a PCND, and 49 patients (32 percent) had undergone the procedure. The two groups were similar in the total number of lateral compartment lymph node metastases (p = 0.455), the maximum diameter of lateral compartment lymph node metastases (p = 0.551), and the number of lateral compartment lymph node levels involved (p = 0.330). ⁽¹⁾ Seventy-one percent of patients in the non-PCND group and 78 percent of patients in the PCND group had received adjuvant radioactive iodine therapy (p = 0.386). ⁽¹⁾

Of the 103 non-PCND patients, 13 (13 percent) had lymph node sampling within the central compartment. Eight of these 13 patients had central nodal disease confirmed on histopathology, with a median of one positive central compartment node with a maximum diameter of 0.55 cm. Among the 49 PCND patients, 37 (76 percent) had central nodal disease confirmed on histopathology, and the median number of nodes removed was seven.

We identified central neck recurrence during the study period in two patients who did not have a PCND. With a median follow-up of 65 months, the five- and ten-year estimated central neck recurrence-free probability was 98.4 percent in the non-PCND group and 93.6 percent in the PCND group (p = 0.133). ⁽¹⁾

During the study period, we also identified lateral neck recurrence in seven patients who did not receive PCND and four patients who had the procedure. The five- and ten-year estimated lateral neck recurrence-free probability was 93.8 percent and 87.8 percent in the non-PCND group, and 91.5 percent and 91.5 percent in the PCND group (p = 0.933), respectively. ⁽¹⁾

The five- and ten-year estimated disease-specific survival was 100 percent and 92 percent in the non-PCND group and 100 percent and 100 percent in the PCND group (p = 0.116), respectively. ⁽¹⁾

Advancing Thyroid Cancer Research

At MSK, we are dedicated to improving oncological outcomes for patients while minimizing the risks and complications of treatments. We support the position that the extent of initial surgery for thyroid cancer patients should be based on evidence showing improved locoregional control or survival.

We are currently conducting nine clinical trials testing innovative treatment approaches for thyroid cancer. These trials include three testing LOXO-292, an investigational drug designed to inhibit cancer growth by blocking RET protein, and two testing whether drugs may enhance the uptake of radioactive iodine in patients with specific gene mutations that limit its response.

The study was funded in part through the National Institutes of Health/National Cancer Institute Cancer Center Support Grant, P30 CA008748.

All study authors declare no competing financial or personal interests.