Background and rationale
cancers, thyroid cancer, microcarcinomas, cancer, paralysis, papillary thyroid cancer, endocrine malignancy, tumors, thyroid cancers
CANCERS, METASTASIS, RECURRENCE, DIFFERENTIATED THYROID CARCINOMA, CANCER, DISEASE, HYPOPARATHYROIDISM, THYROID, DIFFERENTIATED THYROID CANCER, PND, REMISSION, PAPILLARY THYROID CANCER, TUMORS, METASTASES, COMPLICATIONS, THYROID CANCER
For most cancers, the extent of metastasis to regional lymph nodes is a prognostic factor, and prophylactic treatment of lymph node basins for patients with no preoperative evidence of nodal disease (cN0) is often recommended. For differentiated thyroid cancer, however, the prognostic role of prophylactic central compartment neck dissection (PND) associated with total thyroidectomy for patients cN0 constitutes a major controversy for these tumors with an increasing incidence, but a very low mortality rate.Those in favor of PND for whom it is a standard of care cite the low-level evidence suggestingImproved recurrence-free survival (retrospective case series), [A higher rate of recurrence in the presence of lymph node metastases (in some retrospective studies) and the usefulness of a complete staging in the neck to stratify for radioactive iodine treatment, [The technical difficulty of performing a reintervention in the central compartment secondarily, andThe absence of increased permanent complications of PND (in experienced hands). [Opponents of PND cite the low-level evidence suggestingNo effect on oncologic outcomes with PND (retrospective case series), [The low rate of recurrence and mortality even without PND, [The efficacy of radioactive iodine to treat microscopic nodal metastases,A higher risk of complications (hypoparathyroidism and vocal fold paralysis) as compared to -thyroidectomy alone, [The feasibility of reoperation in the central compartment if needed with a relatively low risk of complications (in experienced hands), [An increase in cost with PND. [Despite the low-level conflicting evidence, different professional societies in several countries have published recommendations for or against the routine use of PND, with consequences for patients, physicians, and healthcare providers [This study aims to provide level I evidence with a multicenter prospective open randomized non-inferiority trial comparing bilateral PND with total thyroidectomy to total thyroidectomy alone (and adjuvant radioactive iodine in both groups) for low-risk papillary thyroid cancer patients cT1bT2N0 in terms of the rate of complete remission at 1 year after randomization. We hypothesize that thyroidectomy alone is not inferior to thyroidectomy with PND by more than 5% at 1 year.Differentiated thyroid carcinoma is the most common endocrine malignancy, with an increasing incidence in part related to an improvement in screening for small tumors by neck ultrasound. It accounts for 80% of all thyroid cancers and ranks as the sixth most common cancer in females in incidence, with approximately 10,000 new cases per year in France [However, the role of systematic prophylactic neck dissection (PND) in the absence of suspected neck metastases on preoperative ultrasound (cN0) remains controversial. For example, guidelines from the American Thyroid Association (ATA),[All of these recommendations are grade C (“expert opinion”) due to the lack of high-level evidence in the field. The proponents of systematic PND have underlined its potential effect on recurrence-free survival and disease-specific survival, shown in some retrospective studies, [Current practice is based on conflicting data from studies with low-level evidence and due to the absence of a randomized trial, conflicting recommendations as to the optimal management of low-risk thyroid cancer will prevail [A PubMed® literature search using the terms “thyroid cancer prophylactic neck dissection” found 512 results (accessed January 2023). Among these, Table Summary of publications with the highest level of evidence763409 PND354 TT10151 PND50 TT6030 PND30 TT257153 PND104 TT18193 PND88 TT18,37611,098 PND5583 TTLower LRR in PND group2.52% vs 4.59% (OR=0.65)68233312 PND3511 TT44371969 PND2468 TTLower LRR in PND group1.1% vs 3.4% (Wang TS et alAnn Surg Oncol 2013 [1740745 PND995 TT33311592 PND1739 TTLower LRR in PND group4.7% vs 8.6% (OR=0.65)1264396 PND868 TTAbbreviations: Our study differs from these published studies in the following ways:Our study includes only tumors ≥11 mm (microcarcinomas are not eligible), whereas all of the studies cited in Table Thyroglobulin measurements will be evaluated before and after the administration of RAI to evaluate the effect of RAI ablation and eliminate this bias found in most of these studies in which outcomes were evaluated after RAI ablation in most or all patients;Finally, our study is designed with a non-inferiority margin of 5% and an alpha level set at 0.025, whereas the study by Viola et al. [