This report describes one of the most long-term follow-up (median 20 years) of PTC at a single institution. This is important because it is a report of the long-term results of a large number of patients at a regional top-tier hospital. The facility handles all types of head and neck cancer, and because it is a general hospital, even patients with complications or underlying diseases are treated. Furthermore, as a major regional hospital, many patients are from nearby areas, allowing for long-term follow-up. Compared to other reports, the percentage of stage I disease was low in this study, and not many cases are censored, even after 20 years.2,4,6,7
As more examinations may be performed to detect small tumors due to the improvement and widespread availability of equipment compared to the time we investigated the included cases,8 newer reports may include more stage I cases. In addition, only a few modalities were used to detect distant metastasis preoperatively, as computed tomography and other methods were not as widely available as they are today, and the number of stage IV cases was small. However, distant metastasis was associated with a high mortality rate in this study, and it has been established that the presence or absence of distant metastasis significantly affects prognosis. In our study, there was a significant difference in DSS in the multivariate analyses in terms of age, tumor size, pathological node metastasis, and distant metastasis, similar to previous reports. Considering the era in which the treatment was performed, the accuracy of the preoperative tests was questionable; therefore, this analysis was based on postoperative pathology. Several risk factors have been proposed to determine treatment strategies based on preoperative and intraoperative evaluation.9 One of these is the ATA guidelines, and similar risk factors have also been proposed in Japan.3,5 Although the risk slightly differs depending on the treatment of 1–2 cm tumors and metastatic lymph nodes, these evaluations are based on the TNM classification.
In the TNM stage classification of the AJCC 8th TNM classification, which has been in use since 2018, age was considered, and the stage classification method was based on age 55 years. Ito et al. reconsidered the Japanese Society of Thyroid Surgery (JSTS) guidelines by considering age and found them useful.10 We also divided the TNM staging by age 55 years and performed our analyses based on the risk factors in the ATA guidelines. The prognosis of patients aged < 55 years was relatively good based on DSS (Figure 3A). However, when considering DFS with ATA risk, the possibility of recurrence was different, and follow-up was necessary according to risk (Figure 3B). In this report, aggressive total thyroidectomy and prophylactic neck dissection were seldom performed for thyroid cancer. Therefore, it can be suggested that appropriate treatment at the time of recurrence without extended surgery does not affect the prognosis. It is important to note that the three cases that relapsed after > 20 years all had an age of onset of < 55 years and were considered high-risk by the ATA (Figure 2). There were 103 high-risk cases based on ATA in patients aged < 55 years, with 68 and 35 cases undergoing lobectomy and total thyroidectomy, respectively. Twenty years later, the recurrence rate was approximately 20% in both cases and the primary mortality rate remained the same at approximately 3%. Although aggressive total thyroidectomy may reduce the recurrence rate, we believe that treatment based on tumor localization is acceptable considering the high prognosis. Careful long-term follow-up is essential.
For patients aged ≥ 55 years, DFS at 20 years in stage I was 90.1%. However, the DSS was 100%, indicating that, as in the case of patients aged < 55 years, the prognosis was not affected by appropriate additional treatment, even if recurrence occurred (Figure 4A). Considering that 40% of patients with stage III and IV disease will have a recurrence within 20 years, aggressive treatment, including RAI, should be performed postoperatively in addition to total resection based on appropriate staging in preoperative and intraoperative assessments. However, since patients must be at least 55 years of age and the 20-year survival rate is over 80%, reduction surgery is an option for older patients with underlying diseases. Stage II disease includes a relatively even range of low-risk to high-risk patients in the risk classification by ATA and JTST, and more appropriate treatment can be proposed under various conditions. The critical difference between ATA and JTST high-risk cases is the inclusion of all N cases. According to the TNM classification, all N-positive cases in T1-3 are classified as stage II, and in the ATA, all cases with N are classified as high-risk. In JSTS, the presence of N and ≥ 3 cm of extranodal invasion is classified as high-risk. The guidelines indicate that classification of the N factor is essential for the determining the risk. A study of N+ patients classified as stage II showed that such patients did not have a high recurrence rate or poor prognosis; however, N1b patients had a predominantly poor prognosis (Figure 5A).
The decision regarding the selection of lobectomy versus total thyroidectomy is controversial.11 Some reports recommended total thyroidectomy for tumors more extensive than 1 cm,12 while others reported the absence of a difference in prognosis.13 Although there are subtle differences among reports, stage I tumors are considered low-risk and can be treated by lobectomy. In contrast, stage III and IV tumors are considered high-risk, and total thyroidectomy is recommended.5,14 Although there is no consensus on intermediate-risk cases, the recurrence rate in our study was higher for stage II pN1b cases, suggesting that aggressive treatment may be indicated for N1b cases. In N1b cases, total thyroidectomy was associated with a significantly lower recurrence rate and higher DSS (Figure 5B). In contrast, even in stage II cases, lobectomy without aggressive treatment may be acceptable in N0 and N1a cases. If only N1b in stage II is treated with total thyroidectomy, more than 60% of stage II patients will experience no problems with lobectomy and may be able to avoid taking lifelong oral medication. Total resection eliminates the risk of recurrence in the remaining lobe, and the thyroglobulin level can be used as an accurate indicator of recurrence. However, the thyroid hormones must be considered, and the risk of complications from surgery increases.
Even in patients who undergo lobectomy, it is possible to save many lives by the early detection of recurrence. Extensive follow-up is necessary to make lobectomy acceptable. In addition to blood tests and lung radiography, we perform annual echocardiographic examinations and have a system to immediately perform echo-guided cytological diagnosis when recurrence is suspected. The fact that the hospital is rooted in the community and that many patients come from nearby areas is a major factor in our ability to provide intensive follow-up care. When considering appropriate treatment methods, it is necessary to consider medical factors and the characteristics of each hospital. According to U.S. guidelines, total thyroidectomy is indicated if the tumor is ≥ 1 cm.12 It is understandable that total thyroidectomy, which a home doctor can easily follow, is shown in cases such as in the U.S., where it is difficult to go to a specialized hospital in a wide area of the country. Although total resection is necessary to perform RAI, at least in cases other than stage III, IV, and stage II N1b cases, which have a poor prognosis, lobectomy may be sufficient if the tumor is confined to one side.
This report describes the long-term prognosis of patients with PTC at a single institution. The accuracy of the preoperative diagnosis was thought to be inferior compared to the present period because the target period in this study was not recent as we desired to evaluate long-term data. Therefore, we considered the treatment policy by combining the risk factors reported based on the preoperative diagnosis and stage based on the postoperative diagnosis. The results are similar to many reports and indicate that the TNM classification is useful,7 and the risk is considerably low under the age of 55. For those aged > 55 years, N1b cases classified as stage II and III and above should be treated aggressively. In the future, with the development and widespread availability of equipment, it is expected that the difference between preoperative examination and postoperative results will decrease, and more appropriate treatment policies will be considered. It is also necessary to assess the efficacy of molecularly targeted therapy and the risk of genetic mutations. We hope that future studies will improve the treatment outcomes, especially in high-risk patients.