American Thyroid Association design and feasibility of a prospective randomized controlled trial of prophylactic central lymph node dissection for papillary thyroid carcinoma.
BACKGROUND
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).


RESULTS
We examined the design and feasibility of a multi-institutional prospective randomized 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.


CONCLUSIONS
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.
Department of Surgery, School of Medicine, Yale University, New Haven, Connecticut 06520-8062, USA.
Tobias
T
Carling
Sally E
SE
Carty
Maria M
MM
Ciarleglio
David S
DS
Cooper
Gerard M
GM
Doherty
Lawrence T
LT
Kim
Richard T
RT
Kloos
Ernest L
EL
Mazzaferri
Peter N
PN
Peduzzi
Sanziana A
SA
Roman
Rebecca S
RS
Sippel
Julie A
JA
Sosa
Brendan C
BC
Stack
David L
DL
Steward
Ralph P
RP
Tufano
R Michael
RM
Tuttle
Robert
R
Udelsman
D000328:Adult; D002277:Carcinoma; D002291:Carcinoma, Papillary / Q000601:surgery*; D005240:Feasibility Studies; D005500:Follow-Up Studies; D006801:Humans; D008197:Lymph Node Excision; D008207:Lymphatic Metastasis; D009333:Neck; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design; D018401:Sample Size; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000601:surgery*; D013965:Thyroidectomy; D016896:Treatment Outcome