American Thyroid Association Design and Feasibility of a Prospective Randomized Controlled Trial of Prophylactic Central Lymph Node Dissection for Papillary Thyroid Carcinoma
Tobias Carling, Sally E. Carty, Maria M. Ciarleglio, David S. Cooper, Gerard M. Doherty, Lawrence T. Kim, Richard T. Kloos, Ernest L. Mazzaferri, Peter N. Peduzzi, Sanziana A. Roman, Rebecca S. Sippel, Julie A. Sosa
The role of prophylactic central lymph node dissection in papillary thyroid cancer (PTC) is controversial in patients who have no pre-or intraoperative evidence of nodal metastasis (clinically N0; cN0). The controversy relates to its unproven role in reducing recurrence rates while possibly increasing morbidity (permanent hypoparathyroidism and unintentional recurrent laryngeal nerve injury). Methods and Results: We examined the design and feasibility of a multi-institutional prospective
... zed controlled trial of prophylactic central lymph node dissection in cN0 PTC. Assuming a 7-year study with 4 years of enrollment, 5 years of average follow-up, a recurrence rate of 10% after 7 years, a 25% relative reduction in the rate of the primary endpoint (newly identified structural disease; i.e., persistent, recurrent, or distant metastatic disease) with central lymph node dissection and an annual dropout rate of 3%, a total of 5840 patients would have to be included in the study to achieve at least 80% statistical power. Similarly, given the low rates of morbidity, several thousands of patients would need to be included to identify a significant difference in rates of permanent hypoparathyroidism and unintentional recurrent laryngeal nerve injury. Conclusion: Given the low rates of both newly identified structural disease and morbidity after surgery for cN0 PTC, prohibitively large sample sizes would be required for sufficient statistical power to demonstrate significant differences in outcomes. Thus, a prospective randomized controlled trial of prophylactic central lymph node dissection in cN0 PTC is not readily feasible. T hyroid cancer is the most common endocrine malignancy. In the United States, an estimated 44,670 new cases of thyroid cancer were diagnosed in 2010 with a total of 1690 deaths due to the disease (1). The discrepancy between the total number of cases of all endocrine cancers arising in the thyroid (95.2%) and the total proportion of endocrine cancer deaths (65.8%) reflects the long-term survival associated with thyroid malignancies, given its relatively indolent nature (1). Authors are listed in alphabetical order. Assuming the following newly identified structural disease (i.e., persistent, recurrent or distant metastatic disease) cumulative rates over the study period: Year 1 = 10%, Year 2 = 20%, Year 3 = 25%, Year 4 = 27.5%, Year 5 = 30%, Year 6 = 32.5%, Year 7 = 35% c Assuming the following newly identified structural disease (i.e., persistent, recurrent or distant metastatic disease) cumulative rates over the study period: Year 1 = 3%, Year 2 = 5%, Year 3 = 6%, Year 4 = 7%, Year 5 = 8%, Year 6 = 9%, Year 7 = 10%. 242 CARLING ET AL.