Risk Factors for Central Lymph Node Metastases and Benefit of Prophylactic Central Lymph Node Dissection in Middle Eastern Patients With cN0 Papillary Thyroid Carcinoma

Abstract

BackgroundProphylactic central lymph node dissection (PCLND) for adult patients with papillary thyroid carcinoma (PTC) is still a matter of debate. Data on incidence, risk and benefits of PCLND in Middle Eastern patients is lacking. Therefore, we aimed to identify the incidence and predictive clinico-pathological and molecular marker of PCLND in adult patients with clinically node negative (cN0) Middle Eastern PTC.MethodsThis retrospective study included 942 adult Middle Eastern patients with cN0 PTC who underwent total thyroidectomy (TT) or TT+PCLND. Clinico-pathological associations of central lymph node metastasis (CLNM) were assessed. Multivariate analysis was performed using logistic regression and Cox proportional hazards model.Results213 patients underwent PCLND and 38.0% (81/213) had positive CLNM. Multivariate analysis demonstrated age ≤55 years (Odds Ratio (OR) = 7.38; 95% Confidence Interval (CI) = 1.59 – 34.31; p = 0.0108), tumor bilaterality (OR = 3.01; 95% CI = 1.01 – 9.21; p = 0.0483), lymphovascular invasion (OR = 2.92; 95% CI = 1.18 – 7.23; p = 0.0206) and BRAF mutation (OR = 3.24; 95% CI = 1.41 – 7.49; p = 0.0058) were independent predictors of CLNM in adult PTC. Furthermore, patients who underwent PCLND showed significant association with improved recurrence-free survival (RFS; p = 0.0379). Multivariate analysis demonstrated that PCLND was an independent predictor of improved recurrence-free survival.ConclusionscN0 Middle Eastern PTC patients treated with PCLND showed a significantly better prognosis. PCLND was effective in improving RFS in Middle Eastern PTC patients and should be encouraged for patients with potential risk factors for CLNM.

Genetic Changes in Thyroid Cancers and the Importance of Their Preoperative Detection in Relation to the General Treatment and Determination of the Extent of Surgical Intervention—A Review

“…The role of elective neck dissection in the treatment of PTC without clinically present lymph node metastases remains controversial, especially regarding indications, approach, and surgical extension of treatment [32,[34][35][36][37]40]. Although morbidity and survival rates appear to be similar to those reported for total thyroidectomy alone, the impact of neck dissection VI on local recurrence and long-term survival is still under investigation [36,37,40,45]. Currently, most publications recommend selective indications for elective neck dissection in patients diagnosed with risk factors or combinations of risk factors (most frequently mentioned: BRAF mutations, tumor size, multifocality, extracapsular spread) rather than routinely indicated lymph node procedures [15,[44][45][46].…”

“…The detection of BRAF mutation as a possible predictive factor of occult metastasis could lead to the indication of elective neck dissection of region VI, which in the case of positive metastatic lymph nodes would lead to a reduction of recurrence and refinement of the extent of the disease (staging—conversion from cN0 to pN1a) [ 15 , 41 , 42 , 43 , 44 , 45 , 46 ]. However, the change in surgical treatment intensification (neck dissection routinely indicated) based on the identification of mutations in the preoperative period in cN0 PTC is still controversial because of the potential increased risk of surgical complications (recurrent laryngeal nerve injury, hypoparathyroidism) and its relation to the overall treatment benefit (persistence, recurrence of disease) [ 33 , 34 , 35 , 41 , 42 ].…”

“…In the following section, we present the results of recently published studies that address the general risks (temporary/permanent recurrent laryngeal nerve involvement, temporary/permanent hypoparathyroidism) and benefits (reduced incidence of persistence/recurrence of disease, reduced incidence of lymph node metastasis) of elective neck dissection of region VI in patients with thyroid carcinomas (especially PTC) [ 33 , 34 , 35 , 36 , 37 , 40 ]. We also present the results of studies focusing on performing neck dissections of region VI specifically in patients with BRAF V600E -positive mutation, where BRAF V600E mutation in PTC is correlated with a higher risk of occult metastasis, and it is discussed whether it should be a determining factor for indicating elective neck dissection of region VI under the assumption of improved survival and reduced risk of recurrence of the primary disease [ 15 , 41 , 42 , 43 , 44 , 45 , 46 ].…”

“…Due to the increased risk of temporary and permanent hypoparathyroidism in routinely performed elective neck dissection of the region VI and the different results of studies investigating the relationship of elective neck dissection with disease recurrence and survival in cN0 patients, risk factors related to metastatic spread to the central cervical lymph nodes have recently been studied. In the future, knowledge of these important risk factors should lead to the development of a diagnostic–therapeutic approach in order to predict the occurrence of metastases in cervical lymph nodes (not only central ones) and to indicate an adequate extent of surgical treatment in the preoperative period with regard to the high benefit and low risk of postoperative complications [ 15 , 41 , 42 , 43 , 44 , 45 , 46 ]. In recent studies, the most frequently mentioned predictive molecular factor for the occurrence of occult metastases to central cervical lymph nodes in cNO patients is the BRAF V600E mutation [ 15 , 38 , 39 , 43 , 44 , 45 , 46 ].…”

“…In the future, knowledge of these important risk factors should lead to the development of a diagnostic–therapeutic approach in order to predict the occurrence of metastases in cervical lymph nodes (not only central ones) and to indicate an adequate extent of surgical treatment in the preoperative period with regard to the high benefit and low risk of postoperative complications [ 15 , 41 , 42 , 43 , 44 , 45 , 46 ]. In recent studies, the most frequently mentioned predictive molecular factor for the occurrence of occult metastases to central cervical lymph nodes in cNO patients is the BRAF V600E mutation [ 15 , 38 , 39 , 43 , 44 , 45 , 46 ]. In large meta-analyses, male gender, age, tumor size > 10 mm, multifocality, tumor bilaterality, thyroid capsule affected by tumor, angiolymphatic invasion, and high histological risk have been correlated as additional predictive clinicopathological factors [ 42 , 44 , 45 , 46 ].…”