Clinical evaluation of T2 papillary thyroid carcinoma: a retrospective study conducted at a single tertiary institution

The American Joint Committee on Cancer/Union for International Cancer Control TNM staging system for thyroid cancer defines category T as follows: T0, no evidence of primary tumor; T1, size ≤ 2 cm and intrathyroid; T2, 2cm 4 cm or ETE (sterno-hyoid, sterno-thyroid, thyro-hyoid and omo-hyoid muscle); Q4, others – ETE gross. T2 accounts for only 3% to 13% of all PTC cases in Korea14,15,16. The incidence of T1 PTC has increased due to improved diagnostic modalities and early detection in Korea17. As raw ETE is often seen in thyroid cancer patients, T3 or T4 CTP accounts for a significant proportion18. Meanwhile, T2 PTC accounts for a relatively small portion of all PTC cases.

According to ATA management guidelines, lobectomy alone may be sufficient when used as initial treatment for patients with PTC measuring 1-4 cm but without ETE and without clinical evidence of LN metastasesten. However, the extent of surgery for PTCs measuring 1–4 cm is still controversial. After the release of the 2015 ATA management guidelines, several studies have investigated the extent of surgery in PTCs measuring 1–4 cm19,20,21. Rajjoub et al. showed that lobectomy is not sufficient for T2 PTC. The results showed that 33,816 adults with conventional CTP measuring 1.0 to 3.9 cm had better survival after TT than after lobectomy. This finding was observed especially in patients with a tumor size of 2.0 to 3.9 cm19. Suman et al. found that lobectomy had a significantly negative effect on long-term survival. Excluding high-risk features is important when adopting lobectomy as the definitive surgical treatment for T1b and T2 PTC because of its potential adverse effects on long-term survival.22. In contrast, previous research has found that lobectomy may be appropriate for patients with low-risk differentiated thyroid carcinoma (DTC). Careful risk assessment and stratification can individualize treatment, prevent overtreatment, and ensure a good long-term prognosis with a low risk of recurrence23. Philippo et al. revealed no significant difference in terms of the risk of locoregional recurrence or distant metastasis between the TT and lobectomy groups with pT1-T2 and pN0 PTC. Moreover, compared to lobectomy, TT was correlated with more complications, including postoperative hypoparathyroidism and recurrent laryngeal nerve damage.20. Consistent with Filippo’s study, there was no statistically significant difference in recurrence rate between the TT and lobectomy groups in our study (p = 0.868). Kaplan-Meier analysis of SSM showed no significant difference between the two groups (log-rank test, p=0.877).

If recurrence frequently occurs in the residual thyroid gland, TT, rather than lobectomy, may be recommended. We analyzed recidivism patterns in the study population. In the present study, five (4.6%) patients in the TT group and 6 (4.2%) in the lobectomy group were diagnosed with recurrence. All but one patient in the lobectomy group had a recurrence in the ipsilateral lateral compartment. On the contrary, the recurrence pattern of the TT group varied. Thus, the recurrence occurred mainly in the lateral compartment rather than in the residual thyroid gland after lobectomy.

TT is advantageous because it can improve the accuracy of monitoring by using serum thyroglobulin as a sensitive postoperative marker of residual or recurrent thyroid cancer24. In addition, it allows the use of RAI, which can be used both in postoperative treatment and monitoring25. RAI increases survival rates for patients with intermittent and high risk DTP. However, ATA management guidelines do not recommend RAI ablation in patients with low-risk T2 PTCten. Schvartz et al. showed that RAI after surgery has no survival benefit in a large cohort of patients with low-risk DTP26.

The extent of surgery should not be based solely on the risk of recurrence. TT can lead to various postoperative complications. However, such complications are rare. First, TT is associated with a higher risk of hypoparathyroidism. After thyroidectomy, 19% to 38% and 0% to 3% of patients had transient and permanent hypoparathyroidism, respectively.27. Permanent hypoparathyroidism is associated with multiple complications, including impaired kidney function, gastrointestinal and neuropsychiatric problems, and infections28. Second, TT is also associated with an increased risk of recurrent laryngeal nerve injury. About 0.5% to 5% and 1% to 30% of patients who undergo TT have permanent recurrent laryngeal nerve injury and temporary injury, respectively.29. Third, patients with PTC are relatively young, most in their 40s or 50s at the time of diagnosis.30. Considering that PTC has a good prognosis, patients should be treated with levothyroxine for about 30-50 years after TT. Long-term use of this drug leads to complications including osteoporosis and arrhythmias31.32. Further studies on TT complications, which were not included in the current study, should be performed.

Because the purpose of this study is to observe the general characteristics of patients with T2 CTP, data on patient complications were not initially included. Among the patients included in this study, transient paralysis of the vocal cords was observed in three patients (2.1%) in the lobectomy group and four patients (3.7%) in the TT group. There was no statistically significant difference in terms of transient vocal cord paralysis between the two groups. Permanent vocal cord paralysis was not observed in any patient in the lobectomy group, while it was observed in one patient (0.9%) in the TT group. Transient hypoparathyroidism was not found in the lobectomy group, whereas it occurred in 25 patients (23.1%) in the TT group. These results are consistent with those reported in a recent meta-analysis33.

The LNR is calculated by dividing the number of positive LNs by the number of harvested LNs, and it is used to predict recurrence in other types of cancers34.35. Recently, LNR has been shown to be an important predictor of DFS in PTC36. Schneider et al. assessed 10,955 cases, and results showed NRL to be a strong prognostic factor37. Vas Nunes et al. conducted a retrospective analysis of 198 patients with PTC who underwent TT. The results showed that the LNR was an important independent prognostic factor in PTC and could be used in combination with existing staging systems.38. Our study found similar results. An analysis of the ROC curve was performed to obtain an optimal threshold value of 0.32. Multivariate analysis revealed that an LNR > 0.32 was a significant risk factor for recurrence. In the Kaplan-Meier analysis, the DFS between the high and low LNR groups did not differ significantly (log-rank test, p37. Vas Nunes et al. proposed that an LNR cut-off value of 0.3 may be a prognostic factor38. In this study, the optimal LNR cut-off value was 0.32. Thus, further prospective or multicenter studies should be conducted to determine the optimal LNR cutoff value. The high LNR group was younger and had a greater number of male patients than the low LNR group. This result was consistent with that of several studies. Wang et al. showed that younger patients with a high LNR are at higher risk of PTC39. Kim et al. conducted a large cohort study. The results showed that male patients had a higher number of positive LNs40. Nevertheless, further studies should be conducted to determine the relevance of age and sex for NRL. This study identified the recurrence patterns of patients with T2 PTC. Most recurrences did not occur in the remaining thyroid gland after lobectomy. Even if postoperative pathology findings showed that patients had elevated LNR, we do not routinely recommend thyroidectomy after lobectomy. Short-term follow-up may be useful for patients with T2 PTC who have an elevated LNR after lobectomy.

This study had several limitations due to its retrospective nature. First, the strength of the result has been undermined. Second, the participants came from a single higher education institution. Therefore, this may have caused selection bias and these participants may not reflect the entire patient population. Finally, the follow-up period was relatively short (100.7 ± 18.3 months). Therefore, longer follow-up is needed to predict long-term surgical outcomes of patients with T2 PTC, as it has indolent features. Nevertheless, these limitations could be resolved by conducting a multicenter study in the future.

However, the study also had some advantages. In other words, each patient was followed and standardized laboratory and imaging protocols from a single institution were used. To our knowledge, only a few studies have individually analyzed T2 PTC. Although other studies have previously addressed PTC recurrence, this research differs as it identified patterns of recurrence in the TT and lobectomy groups. This then helps to determine the extent of the surgery.

In conclusion, lobectomy is not associated with a higher risk of recurrence and is feasible in patients with T2 PTC. Additionally, it may be considered in patients without ETE, suspected LN metastases, and intrathyroid lesion. LNR may be an independent risk factor for recurrence in T2 PTC. Thus, short-term follow-up may be recommended for patients with PTC T2 who have a high LNR.

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