Introduction
Thyroid carcinoma is the most common endocrine malignancy, accounting for approximately 3.8% of all newly diagnosed cancer cases (1). Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, accounting for ~85% of all thyroid cancer cases (2,3). It usually has a favorable outcome, with the 10-year survival rate exceeding 90% (4,5). However, previous studies have reported that the recurrence rate is 7-23% following initial surgical treatment (6,7).
Lymph node metastasis is relatively frequent in PTC. However, it is unclear whether it is a risk factor for PTC recurrence. The American Thyroid Association (ATA) 2015, National Comprehensive Cancer Network (NCCN) 2019, and British Thyroid Association (BTA) 2014 are widely known international guidelines (8-10). However, comparisons between the guidelines reveals that small differences in risk factors for PTC recurrence among each guideline can be observed (Table I). This is largely attributed to the guidelines being mainly based on the Union for International Cancer Control/American Joint Commission on Cancer (UICC/AJCC) TNM classification (11). In previous reports, various factors, including age, sex, tumor size, extrathyroidal infiltration, lymphovascular invasion, paratracheal lymph node metastasis and lateral cervical lymph node metastasis have been shown to be associated with the recurrence of PTC (12-14). The main focus of the present study was lymph node metastasis, particularly lateral cervical lymph node metastasis. The difference in recurrence rate, depending on the presence or absence of lateral cervical lymph node metastasis at the time of the initial surgery and the risk factors for lateral cervical lymph node metastasis were investigated herein.
Results
The present study included 59 males (21.5%) and 215 females (78.5%), aged 19-86 years (median age, 66 years). The TNM classification of the patients is presented in Table II. Among the 274 patients, PTC recurred in 20 (7.3%) patients in total. The duration to recurrence and treatment are presented in Table III. Of the 274 participants, 78 (28.5%) presented with lateral cervical lymph node metastasis (Table IV). Since neck dissection was performed only in cases with obvious metastases on pre-operative imaging, there were no cases with no metastases post-operatively.
Age was classified as ≥55 and <55 years, as age is crucial for thyroid cancer staging. No significant differences in age were detected. Similarly, no significant differences were found with respect to sex (Table IV).
Several items revealed significant differences (Table IV). Multivariate analysis of the significantly different items revealed that paratracheal lymph node metastasis and tumor size were independent risk factors for lateral cervical lymph node metastasis (Table V).
As illustrated in Fig. 2, the DFS of patients with lateral cervical lymph node metastasis was significantly lower than that of those without lateral cervical lymph node metastasis. The 10-year DFS rates following initial treatment were 76.8 and 93.8%, respectively (P<0.0001).
Discussion
The prognosis of the majority of patients with PTC is favorable, with 10-year disease-specific survival rates exceeding 90%, and patients who undergo curative surgery have a better prognosis. Additionally, a good prognosis has been frequently reported for patients with PTC (15-17). Recurrence has been reported to occur in ~7-23% of patients with PTC. In addition to TNM, other risk categories that have been proposed for PTC include age, grade, extent and size (AGES), age, metastasis, extent and size (AMES) and metastasis, age, complete resection, invasion and size (MACIS), with the corresponding factors including age, sex, extrathyroidal infiltration, tumor size, lymph node metastasis, distant metastasis, and differentiation by pathological diagnosis (8-11). Although there are some differences of race or in the medical care system, key risk factors are common, indicating that there is universality in factors derived from previous reports. The most critical issue associated with PTC is to reduce the recurrence rate, and thus there is an urgent need to investigate strategies with which to achieve this aim. In the present study, lateral cervical lymph node metastasis was the main focus, which is considered a risk factor for PTC recurrence.
In the univariate analysis, lymphovascular invasion, venous invasion, extrathyroidal infiltration, paratracheal lymph node metastasis and tumor size were designated as risk factors for cervical lymph node metastasis. In the multivariate analysis, paratracheal lymph node metastasis and tumor size at initial treatment were found to be independent risk factors for lateral cervical lymph node metastasis. Extrathyroidal infiltration also tended to be a risk factor, although not significantly. Lymphovascular invasion surely causes a high rate of lymph node metastasis. Actually, 31 out of 64 patients with lymphovascular invasion, or about half, had lateral cervical lymph node metastasis (Table IV). In ATA 2015, NCCN 2019 and BTA 2014, extrathyroidal infiltration and lymph node metastasis (N1) were listed as high-risk factors (8-10). Lateral cervical lymph node metastasis was present in 57 out of 148 patients with extrathyroidal infiltration and in 74 out of 170 patients with paratracheal lymph node metastasis.
As regards the extent of lymph node dissection in the absence of obvious metastases, paratracheal lymph node dissection is recommended from the viewpoint of complications during reoperation; however, it has been reported that prophylactic lateral cervical lymph node dissection may be unnecessary, excluding cases where the primary tumor is large in diameter or distant metastases are detected (18-20). According to the results of the present study, prophylactic lateral cervical lymph node dissection may be considered in patients with obvious pre-operative paratracheal lymph node metastasis.
There was a notable difference in the DFS between patients with and without lateral cervical lymph node metastasis, indicating that patients with lateral cervical lymph node metastasis are more likely to have recurrence. This result is consistent with the aforementioned guideline risk factors. Although it is difficult to eliminate recurrence, the most critical task is to clarify the risk factors for recurrence and to improve the recurrence rate by accumulating such studies. It is suggested that it is necessary to keep accumulating additional cases and conduct more detailed studies.
In conclusion, in the present study, 274 cases of PTC were reviewed and the presence of lateral cervical lymph node metastasis was determined. Paratracheal lymph node metastasis and tumor size were found to be independent risk factors for lateral cervical lymph node metastasis. Japanese guidelines generally recommend prophylactic paratracheal lymph node dissection (18,20). The procedure is relatively simple, and based on the present data, it is that prophylactic dissection may be beneficial. Increase in recurrence rate was observed to be significantly associated with lateral cervical lymph node metastasis.