Previous studies have reported that the rate of regional lymph node metastasis in patients with PTC is approximately 30% up to 80%18,19 and central lymph node metastasis is already present in 40–60% of patients at the time of diagnosis20–22. Other studies demonstrated that the rate of contralateral central neck metastasis in patients with ipsilateral lateral neck metastasis was 34.7% and 5–30% in the final pathology, respectively23,24. Since these rates were relatively high, there has been a controversy as to whether or not surgeons should perform contralateral central neck dissection (CND) without suspicious contralateral central lymph nodes on preoperative imaging. In addition, there have not been many studies on this subject to date, therefore the long term effect of prophylactic contralateral CND in PTC patients with ipsilateral lateral neck metastasis are still unclear. To the best of our knowledge, this study is one of the few studies to investigate the long-term outcome of prophylactic contralateral central neck dissection in PTC patients with ipsilateral lateral neck metastasis.
In our study, male sex, larger tumor size, and greater number of metastatic ipsilateral CLNs significantly increased the risk of LRR, however, ipsilateral CND only did not increase the risk of recurrence (Tables 3 and 4, Figs. 2 and 3). In the ipsilateral CND group, the rate of recurrence in the ipsilateral central or lateral neck was higher than those in the contralateral central or lateral neck (Table 2). There was no significant difference in recurrence regarding CND status with either the ipsilateral or bilateral sides (Figs. 2 and 3).
The point is, recurrence is more likely to occur in the ipsilateral neck, not in the contralateral central neck or lateral neck in this whole study population (Table 2). A previous study reported by Oshima et al. demonstrated that male sex, larger tumor size, ETE, and gross nodal metastasis were associated factors for contralateral lateral neck recurrence25. However, contralateral neck recurrence rarely occurred so it was difficult to analyze risk factors for contralateral recurrence in our study.
Based on our results, we found that ipsilateral CND only was not associated with a higher risk of either overall recurrence or contralateral recurrence. Interestingly, there was no tumor recurrence in the contralateral central neck among the whole study population, regardless of whether bilateral CND was performed. LRR occurred mostly in the ipsilateral thyroidectomy site and/or ipsilateral compartment.
Some studies concluded that microscopic node metastasis occurs frequently, but it does not give rise to the higher recurrence risk seen in clinically detectable macroscopic disease26,27. Randolph et al. reported that microscopic lymph node metastasis appeared to be present in up to 80% of patients, but recurrence rates ranged from 2–6%26. Our study showed that microscopic central neck metastasis was present in 68.5% of patients, and recurrence rate was 7.9%. Hughes DT et al. concluded that there was no significant difference in postoperative Tg level between the thyroidectomy alone group and prophylactic CND group in pathologic N1a patients who presented preoperatively cN027. On the other hand, even if there’s a difference in study population, this study found that Tg was higher in the ipsilateral CND group than in the bilateral CND group with no difference in overall recurrence.
The prevalence of contralateral central neck metastasis in our study was 37.8% (150/397) of patients with ipsilateral lateral neck metastasis. Out of theses 150 patients, preoperative contralateral cN1a was found in only 20 (13.3%) patients, implying that most contralateral central lymph node metastasis is microscopic metastasis. Preoperative contralateral cN1a was not commonly found in PTC patients with ipsilateral lateral neck metastasis (N1b) and we were not even able to ensure that contralateral cN1a increased the likelihood of LRR as well as microscopic contralateral central neck metastasis from this study.
Postoperative complications such as hypocalcemia were higher in patients who underwent bilateral CND than those who underwent ipsilateral CND (Table 4). This is a critical issue in thyroid surgery because hypocalcemia is closely associated with the patients’ quality of life, and all endocrine surgeons should not ignore it.
Given the results above, prophylactic contralateral CND may not be necessary in patients with ipsilateral cN1b as a routine procedure. These retrospective data suggest that PTC patients with ipsilateral N1b presenting with evident lymphadenopathy intraoperatively or on preoperative imaging in the contralateral central compartment should undergo therapeutic contralateral CND. Unless there is an evident contralateral metastatic lymph node preoperatively or a detectable contralateral cN1a intraoperatively, ipsilateral CND may be sufficient surgical treatment of the PTC patients with ipsilateral N1b.
This study had several limitations. First, our study was a non-randomized, retrospective, cohort study. Confounding variables or unmeasured factors may not have been identified, and there was possible surgeon bias in the decision to undergo ipsilateral CND versus bilateral CND. That is, the whole cohort was not treated in a random fashion. Thus, further prospective, randomized trials are needed to resolve this selection bias issue in order to clearly compare recurrence rates between the ipsilateral CND and bilateral CND groups. Second, a longer follow-up period is required to assess recurrence and survival more completely. Third, inter-observer variation in the detection and interpretation of cervical lymph node metastasis and inconsistent surgical management were involved because of the long-term period of data collection. Fourth, our findings may not be applicable to smaller centers without a skilled team such as high volume surgeons or radiologists since the experts’ factor could contribute to the low incidence of recurrence and contralateral recurrence. Performing prophylactic contralateral CND may rather decrease recurrence and help postoperative treatment planning and follow-up in small institutions with less skill in preoperative node evaluation; even this may demonstrate higher microscopic nodal disease. Despite these limitations, this study still has the value of a retrospective study in examining the role of CND in PTC as a prospective randomized trial may not easily feasible28. By analyzing adequate sample size in a single institution, we tried to minimize inadequate statistical power and local institutional variability using specific inclusion factors and follow-up.
In conclusion, This study suggests that bilateral central neck dissection increased surgery-related complications, especially hypocalcemia, and may not reduce the risk of recurrence in PTC patients with unilateral N1b; therefore, surgeons may perform contralateral CND only in the presence of clinically evident or suspected nodal disease.