Management of Recurrent/Persistent Papillary Thyroid Carcinoma: Efficacy of the Surgical Option

It was estimated that over 44,000 people would be diagnosed with thyroid cancer in the United States in 2010 (1). With appropriate initial treatment, the majority of those patients can expect to achieve good disease-specific outcomes. However, up to 30% of patients (2) will suffer persistent disease or recurrences, the majority of which are fortunately localized to cervical lymph nodes. Although recommendations for the initial management of well-differentiated thyroid cancer are well-formulated and have considerable evidence behind them, gathered over many decades of careful follow-up, recommendations for therapeutic options for recurrent or persistent disease have less clarity. Historically, this has been a difficult literature. There have been variations in surgical technique and shifts in the use of adjuvant radioactive iodine therapy. There have been improvements in thyroglobulin assays over time and thus, changing definitions of biochemical cure. We have shifted paradigms for disease detection modalities, performing more frequent TSH-stimulated thyroglobulin assessments since the Food and Drug Administration approval of recombinant human TSH and have dramatically increased the utilization of high-resolution neck ultrasonography. In older studies, the criteria for cure after surgery was often not rigorous, or detailed information on disease assessment postoperatively was not provided. Furthermore, direct comparison of different modalities of therapy and combinations of therapy (e.g. radioactive iodine and/or surgical resection) have been rare, and those studies, such as Coburn et al. (3), usually were not randomized and suffered from significant selection bias. The 2009 Revised American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer recommend surgical management of locoregional disease in the absence of distant metastases with an evidence rating of B (based on fair evidence that the service or intervention can improve important health outcomes) (4). Literature subsequent to that reviewed for the 2009 Revised Guidelines, including the paper by Yim et al. (5) published in this issue of the JCEM, contribute additional information to be considered in the assessment of the efficacy of lymph node dissection for locoregional disease. Specifically, three recent studies suggest that surgical intervention for locoregional recurrence can indeed achieve biochemical remission (undetectable TSH-stimulated serum thyroglobulin).LymphnodedissectionachievesaTSH-stimulatedthyroglobulinof less than1.0ng/ml in29%ofpatients (6) and less than 2.0 ng/ml in 41–46% of patients in one to three lymph node dissections (6, 7). Clayman et al. (8) reported obtaining an undetectable thyroglobulin ( 3 ng/ml) in 71% of informative cases. The paper by Yim et al. (5) describes a careful analysis of a relatively large series of 83 patients who underwent surgical intervention for recurrent/persistent papillary thyroid carcinoma. The authors report achieving a biochemical remission (undetectable TSH-stimulated thyroglobulin less than 1.0 ng/ml) in 51% of patients and less than 2.0 ng/ml in 61% of patients. Additional important findings in this study were that higher preoperative thyroglobulin levelspredicted failure toachieveabiochemical and clinical remission. However, there was only a tendency toward the number of pathological nodes to predict biochemical remission and no impact of the number of removed nodes, number of malignant nodes, extent of reoperation or adjunctive radioactive iodine on achieving