ENEs in Thyroid Cancer Up Risk for Recurrence to Intermediate

Roxanne Nelson, RN, BSN

July 01, 2019

The presence of extranodal extension (ENE) indicates an intermediate risk for recurrence of papillary thyroid carcinoma (PTC), according to new findings.

ENE is the extension of metastatic cells beyond the nodal capsule into the perinodal soft tissue, as determined by surgical pathology results obtained after total thyroidectomy.

The authors say that incorporating ENE into the current risk-stratification system for PTC would allow more accurate treatment decisions.

"The study found that the presence of extranodal extension indicates an intermediate risk for recurrence in papillary thyroid carcinoma. Our findings underscore the value of including ENE in the current system of managing PTC with lymph node metastasis," author Tae Hyuk Kim, MD, PhD, from the Thyroid Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, told Medscape Medical News in an email.

In the study, patients with five or fewer lymph nodes (LNs) but one to three ENEs were found to be at higher risk for recurrence than those with five or fewer LNs but no ENEs.

Additionally, the risk for recurrence in the subgroup with five or fewer LNs and one to three ENEs was similar to that of the three subgroups with more than five LNs.

"The take-home message is that ENE has prognostic significance in PTC, as it does in head and neck cancers, particularly for those with ATA [American Thyroid Association]–low risk," Kim said.

"The presence of ENE in their metastatic lymph nodes confers them ATA-intermediate risk equivalent for structural persistent/recurrent disease," he said.

The study by Hye In Kim, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, and colleagues was published in Thyroid.

ENEs Emerge as a Risk Factor for Recurrence

Physicians currently use the risk-stratification system of the ATA to determine further management options for patients with PTC, including radioactive iodine treatment, degree of thyrotropin suppression, and surveillance. The current system incorporates two LN criteria to stratify nodal disease: the number and largest size of positive LNs.

However, the authors note, the presence of ENE has emerged as an important risk factor for recurrence.

According to the current ATA guidelines, patients with LNs with three or fewer ENEs are at low risk for recurrence (2%). Those with LNs that have more than three ENEs are at high risk for recurrence (estimated 40%).

ENE has not been incorporated into the ATA risk-stratification system for recurrence of PTC for a number of reasons, including the fact that the presence and number of ENEs are closely linked to the number of positive LNs, which is already included as a variable in the system.

"Considering the prognostic significance of ENE, an alternative ATA risk stratification system that includes ENE criteria is needed," the researchers stress.

"However, most studies have focused only on the fact that ENE is a risk factor of recurrence, and have not investigated how to incorporate ENE into the current ATA risk-stratification system taking multi-collinearity into consideration," they explain.

Incorporating ENEs Into Risk Upgrades Many to Intermediate

In this study, Kim and colleagues evaluated the impact of the presence and number of ENEs on recurrence in patients with PTC and studied how to integrate this information into the current ATA risk-stratification system.

The retrospective review included 369 patients with N1 PTC, without distant metastasis, who were treated at a single center in South Korea.

The researchers identified the combination of number of positive LNs and LNs with ENE that had the highest C-index. Statistical models were developed to assess the association between the various combinations and recurrence, with or without adjusting for conventional prognostic factors.

They then estimated the effect of incorporating ENE into the current ATA risk-stratification system.

The median age of participants was 42.0 years, and 63% were women. The median largest positive LN size was 0.6 cm, and the median number of positive LNs was five. ENEs were detected in 193 patients (52.3%).

At a median follow-up of 40 months, 35 patients (9.49%) experienced structural persistent/recurrent disease.

The recurrence rate for the patient subgroup that had five or fewer LNs and one to three ENEs (7/61 [11.5%]) was more than three times higher than the subgroup that had five or fewer LNs without ENE (5/129 [3.9%]; adjusted hazard ratio [HR] = 3.42; P = .050) and was similar to that of the subgroup that had more than five LNs without ENE (recurrence rate, 6/47 [12.8%]; adjusted HR = 4.47; P = .028).

Using the current risk-stratification system, the patients in the latter subgroup, who had more than five LNs without ENE, would be classified as being at intermediate risk.

When incorporating ENE into the risk stratification, almost a third (32.8%) of patients with five or fewer LNs but with ENE were upstaged from the low-risk group to the intermediate-risk group.

Those with more than five LNs with ENE remained in the intermediate-risk group, because there was no further increase in risk for recurrence with regard to the presence or number of ENE.

"By incorporating ENE into the current risk-stratification system, physicians can make more accurate decisions about how to manage PTC," the authors conclude.

The authors have disclosed no relevant financial relationships.

Thyroid. Published online May 30, 2019. Full text

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