Treatment of Recurrent or Persistent Cervical Node Metastases in Differentiated Thyroid Cancer: Deceptively Simple Options

Abstract

Occasionally in medicine a clinical situation that appears simple on the surface is, in reality, much more difficult and complex. Such is the case with the common occurrence (estimated to be as frequent as 30%) of recurrent or persistent papillary thyroid cancer identified in cervical lymph nodes (1, 2). Given the frequency of this circumstance, it would be expected that there would be a large number of prospective, randomized trials assessing the effectiveness of various treatment modalities. In fact, no such trials exist, and the literature represents retrospective studies with a relatively small number of patients. There are several potential (not mutually exclusive) approaches to such patients, including observation, surgery, radioactive iodine therapy, and ethanol injection. The clinical issue is how to approach these patients when there is apparent recurrence or persistence of cervical lymph nodes after initial therapy, which would usually include a thyroidectomy with radioactive iodine therapy. The American Thyroid Association guidelines (3) note that development of a recurrence is associated with a higher mortality, but the clinical benefit of diagnosing and treating small-volume recurrent disease that was detected by sensitive techniques is unclear. In the absence of distant metastases, surgery is favored for cervical lymph node recurrence (3). For patients with recurrent or persistent cervical nodal disease, comprehensive compartment and/or central neck dissection should be performed (3). Limited lateral and/or central compartment dissection is considered a reasonable alternative to more comprehensive neck dissection (3). Several basic questions arise before the issue of appropriate treatment can be considered. How often do cervical lymph nodes grow and cause significant local disease (e.g. tracheal or esophageal invasion or vascular invasion with bleeding)? These circumstances are thought to be extremely rare, especially in patients already preselected for relatively nonaggressive disease. Do local cervical metastases cause distant metastases? Recent studies have led to theories that cancer metastases from the original site involve multiple events including epithelial to mesenchymal transition, and local and distant invasion, each involving a complex series and interactions of genes and proteins, and a receptive distant host site (4). Cancer cells have been found to circulate. Furthermore, there is evidence that local and distant metastases can return to the site of the original tumor and reseed the primary tumor (4, 5). Therefore, it is conceivable that papillary thyroid cancer residing in cervical lymph nodes could relate to progressive primary and distant tumor growth. A corollary question is whether removal of a portion of the cervical node mass would relate to improvement in clinical parameters such as disease-free survival, morbidity, and mortality. It is unknown whether the number or localization of involved cervical nodes or the extent of tumor involvement in an involved cervical lymph node is associated with a worse clinical course. There are no controlled studies comparing different therapeutic approaches to these issues. Given that definitive answers to these important questions are not known, we have to rely on clinical studies to provide guidance on how to approach these patients. In this issue of the JCEM, Robenshtok et al. (6) report that monitoring selected low-risk individuals with recurrent or persistent cervical papillary thyroid cancer in lateral lymph nodes is a reasonable option in many patients. Excluding from analyses patients with aggressive histology or clinical features and using sonographic criteria, they