Article

American Thyroid Association Design and Feasibility of a Prospective Randomized Controlled Trial of Prophylactic Central Lymph Node Dissection for Papillary Thyroid Carcinoma

Department of Surgery, School of Medicine, Yale University, New Haven, Connecticut 06520-8062, USA.
Thyroid: official journal of the American Thyroid Association (Impact Factor: 3.84). 03/2012; 22(3):237-44. DOI: 10.1089/thy.2011.0317
Source: PubMed

ABSTRACT 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).
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.
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.

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Available from: Brendan C Stack, Mar 30, 2015
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    • "Nevertheless, it failed to demonstrate beneficial effects on recurrence and long-term survival , based on strong support data [21] [22]. Certainly, prophylactic LD may reduce postoperative Tg, favoring follow-up but increasing the morbidity of thyroidectomies [22]. According to ML White et al. [4], the rates of permanent hypoparathyroidism and of unintentional permanent recurrent laryngeal nerve injury increased respectively from 1 to 2% and 0e5.5% to 0e14.3% and 0e5.7%, in case of RCLD associated with TT. "
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    ABSTRACT: Introduction: Lymph nodal involvement in papillary thyroid cancers is very common, but the role of lymph node dissection is still controversial. Surgeons are consequently divided between opposed to and in favor of routine central neck dissection associated with total thyroidectomy. Methods: Clinical records of 210 patients undergoing from January 2000 to December 2006 total thyroidectomy without routine lymph node dissection were retrospectively evaluated. One hundred and ninety eight patients (94.2%) underwent radioiodine ablation as well, followed by Thyroid Stimulating Hormone suppression therapy. In patients with loco regional lymph nodal recurrence, central (VI) and ipsilateral (III-IV) lymph node dissection was performed. Results: Incidence of permanent hypoparathyroidism (iPTH < 10 pg/ml) and permanent vocal fold paralysis were respectively 1.4% and 1.9%. After an 8-year mean follow-up, the rate of loco regional recurrence was 4.2%-9/210 patients. In these cases selective lymph node dissection was carried out without complications. Discussion: The role of neck dissection in papillary thyroid cancer management, is still subject of research and controversial regarding routine or therapeutic indications, surgical extension, its impact on local recurrence and survival. Conclusion: A low loco regional recurrence rate may be observed after total thyroidectomy without prophylactic lymph node dissection. Lymph nodal recurrences were more frequent in young male patients, sometime affected by follicular variant, in each case less than 2 cm. There is a general agreement about the extension of therapeutic lymph node dissection, while routine central neck dissection is still controversial and may be indicated in high risk patients. (C) 2014 Published by Elsevier Ltd on behalf of Surgical Associates Ltd.
    International Journal of Surgery (London, England) 05/2014; 12. DOI:10.1016/j.ijsu.2014.05.010 · 1.65 Impact Factor
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    • "Personal conviction is supported by rates of reoperation due to recurrence, survival over time, laboratory index trends. Unfortunately, there isn't any decisive contribution to the discussion due to the lack of randomized prospective trials and the explanations of this lack have been explained quite thoroughly in a recent article regarding this issue [3]. Therefore, we wish to make a contribution by expounding our convictions starting from our personal experience. "
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    ABSTRACT: Aims of the study: The aim of this retrospective study was to appraise the impact of central neck dissection (CND) when treating papillary thyroid carcinoma (PTC) and identifying predictors of tumour recurrence by analysing the results and complications related to this surgical procedure. Materials and methods: The study examined the histories of 347 patients with PTC, divided into two groups: group A including 284 patients who underwent total thyroidectomy (TT) only; group B including 63 patients who underwent TT and CND and possible lateral neck dissection (LND). Results: The patients in the B group were younger than those in the A group (an average of 44.5 vs. 48.6; p = 0.03) and their tumours were larger (1.91 cm vs 1.27 cm, p = 0.001). Multifocality, extra-capsular extensions of the neoplastic mass and high cell histological variant were more prevalent in the B group. The incidence of permanent hyperparathyroidism was higher in group B than in group A (25.4% vs 9.5%, p = 0.0006). Recurrence of disease and the numbers requiring reoperation were also higher in group B: (24.1% in group B vs 6.6 in group A, p < 0.0001). Patients classified as clinically N0 at their first operation and who were most probably clinically N1, totalled 6.6%. Conclusions: Our data show that only extra-capsular extension may be considered a predictor of recurrence. The findings of our study support the idea of carrying out "therapeutic" CND only in cases of preoperative or macroscopic intraoperative clinical evidence of lymph-node involvement.
    International Journal of Surgery (London, England) 05/2014; 12. DOI:10.1016/j.ijsu.2014.05.053 · 1.65 Impact Factor
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    • "Several authors wrote of their experiences but there isn't any prospective randomized trial decisive contribution to the discussion [3]. Indication for prophylactic CND in cN0 appears to be correlated with incidences of postoperative complications. "
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    ABSTRACT: Aims of the study: The aim of this retrospective study was to appraise the impact of central neck dissection (CND) when treating papillary thyroid carcinoma (PTC) and identifying predictors of tumour recurrence by analysing the results and complications related to this surgical procedure. Materials and methods The study examined the histories of 347 patients with PTC, divided into two groups: group A including 284 patients who underwent total thyroidectomy (TT) only; group B including 63 patients who underwent TT and CND and possible lateral neck dissection (LND). Results The patients in the B group were younger than those in the A group (an average of 44.5 vs. 48.6; p = 0.03) and their tumours were larger (1.91 cm vs 1.27 cm, p = 0.001). Multifocality, extra-capsular extensions of the neoplastic mass and high cell histological variant were more prevalent in the B group. The incidence of permanent hyperparathyroidism was higher in group B than in group A (25.4% vs 9.5%, p = 0.0006). Recurrence of disease and the numbers requiring reoperation were also higher in group B: (24.1% in group B vs 6.6 in group A, p <0.0001). Patients classified as clinically N0 at their first operation and who were most probably clinically N1, totalled 6.6%. Conclusions Our data show that only extra-capsular extension may be considered a predictor of recurrence. The findings of our study support the idea of carrying out "therapeutic" CND only in cases of preoperative or macroscopic intraoperative clinical evidence of lymph-node involvement.
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