Abstract
This study aimed to evaluate the impact of periodic neck ultrasonography (US) on postoperative surveillance for locoregional disease control of patients with low- and intermediate-risk papillary thyroid carcinoma (PTC) who underwent total thyroidectomy. This retrospective cohort study included patients with PTC who underwent total thyroidectomy and central neck dissection at our institution between January, 2000 and December, 2016. The patients were divided into two groups: the physical examination (PE) group (follow-up by PE without periodic US) and the US group (follow-up by PE with periodic US). Serum thyroglobulin levels were measured periodically in both groups. Propensity score matching was used to rigorously balance the significant variables and assess the 10-year postoperative outcomes between the groups. Of the 189 patients, 150 were included after matching (75 in each group). There were no significant differences between the two groups in terms of background characteristics. The median follow-up period was 127.9 months. There was no significant difference in locoregional relapse-free survival between the PE and US groups (97.0 vs. 98.7%, p = 0.541). The overall survival was 96.7% and 98.7% in the PE and US groups, respectively, with no significant difference (p = 0.364). This study demonstrated that the addition of periodic US to PE for postoperative surveillance of patients with low- and intermediate-risk PTC who underwent total thyroidectomy did not significantly affect locoregional control.
Introduction
Papillary thyroid carcinoma (PTC) is a differentiated thyroid cancer (DTC) that accounts for the vast majority (90%) of all malignant thyroid tumors [1]. Surgical resection and radioactive iodine (RAI) are the recommended primary treatment modalities for PTC [2]. The prognosis for most patients with PTC is favorable, with a 10-year disease-specific survival of >90%. However, PTC with invasion of the trachea or esophagus and massive lymph node metastases pose a high risk of recurrence, and cases with progressive distant metastasis can be fatal [3]. Several clinical guidelines recommend follow-up based on stage and risk classification for management according to the risk of recurrence. Ultrasonography (US) is a widely used method for detecting locoregional recurrences after thyroidectomy [4]. According to the American Thyroid Association (ATA) guidelines, 6–12 months after total thyroidectomy (TT), which is the initial therapy, neck US is recommended to evaluate the thyroid bed along with central and lateral cervical nodal compartments based on the risk of recurrence (classified as low, intermediate, or high) and performed periodically thereafter along with physical examination (PE) [2]. For patients with PTC who underwent TT, the European Thyroid Association (ETA) guidelines do not recommend annual US for ETA low-risk patients and recommend annual US for high-risk patients, depending on pathological stage and serum thyroglobulin (Tg) levels [5]. On the other hand, 45.4% of physicians involved in thyroid cancer care follow-up patients with low-risk recurrence of PTC using routine US in long-term management [6], and most physicians in Japan also perform annual US after TT.
Although US is non-invasive, it is an operator-dependent procedure that can lead to high false-positive rates [7]. US may be more sensitive than Tg measurement or whole-body scan (WBS) and can identify small lymph node metastases [8]. However, whether the detection of such subclinical recurrent lesions leads to a beneficial prognosis for patients with PTC is controversial [9]. Moreover, over a median follow-up duration of 5–10 years, structural disease recurrence was identified in less than 1–2% of patients with low-risk DTC according to the ATA guidelines and in 8% of those with intermediate-risk who underwent thyroid surgery without RAI ablation as the initial therapy [2]. Therefore, the impact of periodic US on locoregional control after thyroid surgery in patients with low- and intermediate-risk PTC needs to be further investigated.
This study aimed to analyze the impact of periodic neck US on postoperative surveillance for locoregional disease control of patients with low- and intermediate-risk PTC who underwent TT.
Materials and Methods
Patients and data collection
This single-center retrospective cohort study included patients with PTC who underwent TT and central neck dissection (CND) at Nagoya University Hospital between January 1, 2000, and December 31, 2016. Patients with available surveillance data for more than five years after the initial surgery were evaluated in this study. Patients with papillary thyroid microcarcinoma (pT1aN0M0), gross extrathyroidal extension (pT4), distant metastases, or unavailable data were excluded from the study. The histological diagnosis of PTC was made and the patients were classified according to the Union for International Cancer Control (UICC) Staging System (8th edition). ATA risk classification was performed according to the results of pathological examination [2]. Thyroid-stimulating hormone (TSH) suppression therapy and postoperative RAI therapy (remnant ablation with 30 mCi) were determined at the physician’s discretion based on each patient’s general condition, pathological features, and risk of recurrence. TSH suppression was defined as 0.1 mU/L in accordance with the ATA guidelines [2].
Ethics
The study was conducted in accordance with the tenets of the Declaration of Helsinki and approved by the Ethics Committee of Nagoya University Hospital (approval number: 2023-0388). All patients provided consent for the use of their clinical data in the form of opt-outs on the website.
Clinical follow-up
Patients were followed-up with PE and measurement of Tg and anti-Tg antibody at 3–6 months intervals during the first year after surgery and at 6–12 months thereafter on the basis of the clinical course and individual patient risk of recurrence.
PE evaluation
Outpatient physicians palpated the thyroid bed and all lymph node compartments in the neck. PE abnormalities were defined as cervical lymph nodes or cervical nodules with at least one of the following characteristics: approximately ≥10 mm diameter, poor mobility, and hard. If PE revealed suspicious lesions, US-guided fine-needle aspiration (FNA) (cytology and Tg measurement) was performed at the physician’s discretion.
Neck US evaluation
Neck US was performed annually using a linear, high-resolution, 18-MHz transducer by experienced thyroid surgeons as part of routine surveillance in accordance with a standard protocol that included gray-scale and color Doppler US of the thyroid bed and all neck lymph node compartments. US abnormalities were defined as cervical lymph nodes with at least one of the following features: microcalcifications, cystic aspect, peripheral vascularity, and ≥8–10 mm in their smallest diameter [2, 10]. In addition, thyroid bed nodules with a hypoechoic appearance and internal vascularity were also defined as US abnormalities [11]. Normal US findings were defined as cervical lymph nodes with normal morphology or absence of thyroid bed nodules or cervical lymph nodes. For suspicious lesions evident on US, US-guided FNA was performed at the physician’s discretion. Alternatively, for patients undergoing US as part of routine surveillance, suspicious lesions were carefully followed-up with repeat US after 6 or 12 months at the physician’s discretion.
Outcomes
Patients were classified into the following two groups: patients who were followed-up by PE without periodic US surveillance were categorized into the “PE group,” and patients who underwent at least one periodic US surveillance in addition to PE were defined as the “US group.” Diagnosis of structural neck recurrence was evaluated by cytological analysis and/or Tg measurement using FNA. A US scan was considered true-positive if there was evidence in the form of cytology or Tg measurement by US-guided FNA. If no supporting evidence was found or the suspicious lesion was not revealed by careful follow-up with US, it was considered false-positive. The background characteristics of patients in both groups were adjusted using propensity score matching. The primary endpoint of this study was the evaluation of the impact of neck US on locoregional disease control during routine surveillance after TT by analyzing locoregional relapse-free survival, and the secondary endpoints included disease-specific survival and overall survival.
Propensity score matching
Propensity score matching was used to rigorously balance the significant variables included in the analysis. Propensity scores were estimated using a logistic regression model based on eight covariates: ≥ or <55 years of age, sex, UICC pathological T factor, UICC pathological N factor, UICC pathological Stage, TSH suppression therapy, postoperative RAI therapy, and ATA risk classification. One-to-one matching without replacement was performed using the nearest-neighbor matching method with 0.2 caliper width. After matching, pairs with matched scores were used in subsequent analyses.
Statistical analysis
Association between each group and clinicopathological factors were analyzed using the Chi-square test for categorical variables and the Mann-Whitney test for numerical variables. Locoregional relapse-free survival, disease-specific survival, and overall survival were calculated using the Kaplan-Meier method, and survival curves were compared using the log-rank test. All statistical analyses were performed using JMP 16 software (SAS Institute, Inc., Cary, NC, USA), and the level of significance was set at p < 0.05.
Results
Patient characteristics
Fig. 1 shows the flowchart of the patient enrollment process. A total of 189 patients fulfilled our inclusion criteria (102 in PE and 87 in US groups) before propensity score matching. After one-to-one matching, 150 patients were included in this retrospective study (n = 75 in each group), all of whom were classified as low- or intermediate-risk according to the ATA risk classification. The median follow-up period was 127.9 months (range: 60.4–277.2 months). Table 1 shows the clinical characteristics of the patients before and after matching. Before matching, the PE group included more patients with ≥55 years of age and pathological Stage II disease than the US group (p = 0.032 and p = 0.019, respectively). In contrast, significantly more patients in the US group received postoperative RAI therapy than did those in the PE group (p = 0.002). After matching, there were no significant differences in background data between the two groups, and no patients in either group received postoperative RAI therapy.
Fig. 1
Flowchart demonstrating the enrollment process of the study participants.
Table 1 Patient characteristics before and after propensity score matching
|
Unmatched comparison |
Matched comparison |
PE group
(n = 102) |
US group
(n = 87) |
p-value |
PE group
(n = 75) |
US group
(n = 75) |
p-value |
| Age (years) |
55 (17–81) |
48 (15–77) |
0.146 |
50 (17–72) |
48 (15–77) |
0.800 |
| Age |
|
|
0.032* |
|
|
0.864 |
| <55 |
51 (50.0%) |
57 (65.5%) |
|
49 (65.3%) |
48 (64.0%) |
|
| ≥55 |
51 (50.0%) |
30 (34.5%) |
|
26 (34.7%) |
27 (36.0%) |
|
| Follow-up period (months) |
153.2 (60.4–277.2) |
128.1 (60.6–264.3) |
0.249 |
133.7 (60.4–277.2) |
122.9 (60.6–263.1) |
0.280 |
| Sex |
|
|
0.504 |
|
|
0.500 |
| Male |
14 (13.7%) |
15 (17.2%) |
|
10 (13.3%) |
13 (17.3%) |
|
| Female |
88 (86.3%) |
72 (82.8%) |
|
65 (86.7%) |
62 (82.7%) |
|
| UICC pathological T |
|
|
0.922 |
|
|
0.986 |
| T1a |
7 (6.9%) |
6 (6.9%) |
|
5 (6.7%) |
6 (8.0%) |
|
| T1b |
45 (44.1%) |
35 (40.2%) |
|
33 (44.0%) |
31 (41.3%) |
|
| T2 |
28 (27.5%) |
29 (33.3%) |
|
23 (30.6%) |
23 (30.7%) |
|
| T3a |
3 (2.9%) |
3 (3.5%) |
|
2 (2.7%) |
3 (4.0%) |
|
| T3b |
19 (18.6%) |
14 (16.1%) |
|
12 (16.0%) |
12 (16.0%) |
|
| UICC pathological N |
|
|
0.498 |
|
|
0.611 |
| N0 |
35 (34.3%) |
34 (39.1%) |
|
26 (34.7%) |
29 (38.7%) |
|
| N1a |
67 (65.7%) |
53 (60.9%) |
|
49 (65.3%) |
46 (61.3%) |
|
| UICC pathological Stage |
|
|
0.019* |
|
|
1.000 |
| I |
65 (63.7%) |
69 (79.3%) |
|
60 (80.0%) |
60 (80.0%) |
|
| II |
37 (36.3%) |
18 (20.7%) |
|
15 (20.0%) |
15 (20.0%) |
|
| TSH suppression therapy |
|
|
0.111 |
|
|
0.327 |
| Suppressed |
49 (48.0%) |
53 (60.9%) |
|
36 (48.0%) |
42 (56.0%) |
|
| Un-suppressed |
51 (50.0%) |
34 (39.1%) |
|
39 (52.0%) |
33 (44.0%) |
|
| Unknown |
2 (2.0%) |
0 (0.0%) |
|
0 (0.0%) |
0 (0.0%) |
|
| Postoperative RAI therapy |
|
|
0.002* |
|
|
N/A |
| RAI |
0 (0.0%) |
8 (9.2%) |
|
0 (0.0%) |
0 (0.0%) |
|
| No-RAI |
102 (100.0%) |
79 (90.8%) |
|
75 (100.0%) |
75 (100.0%) |
|
| Serum Tg status-FU1y |
|
|
0.262 |
|
|
0.209 |
| Tg <1 ng/mL, TgAb-negative |
29 (28.4%) |
37 (42.5%) |
|
19 (25.3%) |
31 (41.3%) |
|
| Tg ≥1 ng/mL, TgAb-negative |
10 (9.8%) |
7 (8.1%) |
|
8 (10.7%) |
4 (5.3%) |
|
| Tg <1 ng/mL, TgAb-positive |
19 (18.6%) |
16 (18.4%) |
|
15 (20.0%) |
14 (18.7%) |
|
| Tg ≥1 ng/mL, TgAb-positive |
1 (1.0%) |
0 (0.0%) |
|
1 (1.3%) |
0 (0.0%) |
|
| Others |
43 (42.2%) |
27 (31.0%) |
|
32 (42.7%) |
26 (34.7%) |
|
| ATA risk classification |
|
|
0.598 |
|
|
0.742 |
| Low |
43 (42.2%) |
40 (46.0%) |
|
32 (42.7%) |
34 (45.3%) |
|
| Intermediate |
59 (57.8%) |
47 (54.0%) |
|
43 (57.3%) |
41 (54.7%) |
|
Data are expressed as the median (range) or number (%). *p < 0.05.
ATA, American Thyroid Association; FU1y, follow-up one year after surgery; N/A, not applicable; PE, physical examination; RAI, radioactive iodine; Tg, thyroglobulin; TgAb, anti-thyroglobulin antibody; TSH, thyroid-stimulating hormone; UICC, Union for International Cancer Control; US, ultrasonography.
When we evaluated the structural neck recurrence of our cohort after matching, there was no significant difference in locoregional relapse-free survival (10-year locoregional relapse-free survival rate, PE group vs. US group; 97.0% vs. 98.7%, p = 0.541; Fig. 2A). As the secondary endpoint, no patients in either group died of PTC during the follow-up period (p = not applicable, Fig. 2B), and the overall survival (10-year overall survival, PE group vs. US group; 96.7% vs. 98.7%, p = 0.364; Fig. 2C) was not significantly different between the two groups. The postoperative outcomes before matching were consistent with those after matching (Supplementary Fig. 1).
Fig. 2
Postoperative outcomes of the physical examination group versus the ultrasonography group of patients after propensity score matching. The vertical whiskers indicate censoring. (A) Locoregional relapse-free survival. (B) Disease-specific survival. (C) Overall survival. CI, confidence interval; HR, hazard ratio; PE, physical examination; US, ultrasonography.
The clinical outcome of each study cohort is shown in Fig. 3. Table 2 shows the clinical features and outcomes of the patients who underwent FNA in both groups. In two patients (2.7%) in the PE group, lymph nodes suspicious for recurrence were palpated in the left supraclavicular region, and recurrence was confirmed by FNA. Among the 75 patients in the US group, 16 (21.3%) demonstrated US abnormalities. In patients exhibiting US abnormalities, the specific features identified within the cervical lymph nodes included diameter enlargement in 13 cases, microcalcifications in one case, and cystic aspect in one case. Notably, lymph node enlargement was also observed in the patient with cystic aspect. The remaining two patients had hypoechoic nodules in the thyroid bed, and US abnormalities were observed more than five years after surgery in both patients. Three (4.0%) out of 75 patients in the US group had a locoregional recurrence. US findings in these three patients demonstrated cervical lymphadenopathy in the lateral compartments in all cases, one of which also exhibited cystic aspect. One of the three patients with locoregional recurrence was not confirmed by palpation, and the description regarding palpation was unknown in two patients. Of the remaining 13 patients with US abnormalities, three were determined to be benign by cytological analysis, and 10 continued to be carefully followed-up by US, but no recurrence was confirmed. Thirteen patients were classified as false-positive, with a rate of 18.1% (95% confidence interval 10.9–28.5%). US findings in the 13 patients with false-positives showed lateral neck lymphadenopathy in 10 cases, microcalcifications in the lateral cervical lymph node in one case, and hypoechoic nodules in the thyroid bed in the remaining two cases. Supplementary Fig. 2 shows the representative US images of the patients with locoregional recurrence and those with false-positives. The lesions in all five patients with recurrence in both groups were located in the lateral cervical nodal compartments. Four of the five patients with recurrence underwent lateral neck dissection, and one patient refused surgery and was carefully monitored. The clinical course of cases with abnormal findings in either the PE or US group is separately shown in the swimmer plot (Fig. 4). The clinical outcome and clinical course before matching are shown in Supplementary Fig. 3 and Supplementary Fig. 4. Among patients with US abnormalities, the US/4 case in Table 2 showed recurrence 59 months after surgery; however, as shown in Fig. 4 and Supplementary Fig. 4, false-positives tended to occur more frequently within five years of the initial surgery.
Fig. 3
Clinical outcome of each study cohort after matching. FNA, fine-needle aspiration; US, ultrasonography.
Table 2 Clinical features and outcome of eight patients undergoing FNA
| Group/Patients No. |
Age/Sex |
UICC pStage |
ATA risk classification |
LN size (mm)a |
Microcalcification/Cystic aspectb |
Serum Tg (ng/mL)c |
Recurrence |
Recurrence site |
DFI from initial surgery (months) |
Salvage surgery |
Surgical complication |
Outcome |
Follow-up (months) |
| PE/1 |
53/M |
I |
Intermediate |
N/A |
— |
66.9 |
Yes |
Lateral neck LN |
85 |
LND |
None |
NED |
91 |
| PE/2 |
71/F |
II |
Intermediate |
35 |
— |
1.4 |
Yes |
Lateral neck LN |
92 |
LND |
None |
NED |
99 |
| US/1 |
71/F |
II |
Low |
15 |
— |
0.1 |
No |
— |
— |
— |
— |
NED |
76 |
| US/2 |
22/F |
I |
Intermediate |
7.6 |
Microcalcification |
0.4 |
No |
— |
— |
— |
— |
NED |
133 |
| US/3 |
57/F |
II |
Low |
N/A |
— |
N/A |
Yes |
Lateral neck LN |
143 |
LND |
None |
NED |
191 |
| US/4 |
32/F |
I |
Low |
20 |
— |
0.1 |
Yes |
Lateral neck LN |
59 |
LND |
None |
NED |
216 |
| US/5 |
30/M |
I |
Intermediate |
10 |
Cystic aspect |
1.1 |
Yes |
Lateral neck LN |
137 |
refused |
— |
AWD |
250 |
| US/6 |
31/F |
I |
Low |
11 |
— |
0.6 |
No |
— |
— |
— |
— |
NED |
256 |
aLN diameter measured on US at the time of FNA. bLN findings on US at the time of FNA. cSerum Tg levels at the time of FNA.
ATA, American Thyroid Association; AWD, alive with disease; DFI, disease-free interval; F, female; FNA, fine-needle aspiration; LN, lymph node; LND, lateral neck dissection; M, male; N/A, not available; NED, no evidence of disease; PE, physical examination; Tg, thyroglobulin; UICC, Union for International Cancer Control; US, ultrasonography.
Fig. 4
Clinical course of cases with abnormal findings after matching. PE, physical examination; US, ultrasonography.
Discussion
The present study demonstrated that the addition of periodic neck US to PE during routine surveillance of patients with low- and intermediate-risk PTC who underwent TT did not result in significant differences in terms of locoregional relapse-free survival, disease-specific survival, and overall survival.
The current trend in the treatment of PTC involves a more personalized approach, and it is important to use appropriate surveillance tools and follow-up strategies depending on the risk of recurrence. It is controversial whether patients with PTC would benefit from early detection of clinically asymptomatic recurrence using routine US as a surveillance tool [9]. Cervical US can detect nodules with a diameter of approximately 2–3 mm [12]; however, 18% of lymph nodes displaying suspicious features on US are histologically diagnosed as benign [5]. In the present study, US abnormalities were noted in 16 patients with PTC classified as having a low or intermediate recurrence risk according to the ATA risk stratification system during the follow-up period, and the false-positive rate was 18.1% (13/72). Of the 13 patients with false-positives, three were confirmed to have no structural neck recurrence by FNA, and 10 required additional US beyond periodic US. No patients with false-positives showed evidence of recurrence during the subsequent follow-up period. This result is consistent with previous studies demonstrating that periodic US in patients with PTC with serum Tg levels <1 ng/mL classified as ATA low or intermediate recurrence risk, is associated with a high rate of false-positives and low rates of structural recurrence detection [13-15]. The reason why there were many false-positives within five years of the initial surgery in our study was presumably because of the occurrence of locoregional recurrence at a late stage, which was reflected by the slow growth of PTC, and the fact that larger normal lymph nodes were also identified as abnormal by US. Only one previous single-arm prospective study evaluated the need for routine US in patients with low- and intermediate-risk PTC who underwent TT and RAI [16]. The study suggested that when no apparent persistent disease was confirmed by US and WBS in the first-year postoperative surveillance, routine US may be omitted for five years after surgery unless Tg ≥1 ng/mL. In our study, none of the patients underwent postoperative RAI, and some patients had serum Tg levels ≥1 ng/mL. However, even with a median follow-up period of more than 10 years, not only did the locoregional recurrence rate remain low (3.3%, 5/150), but the addition of periodic US to PE for postoperative surveillance also did not significantly affect locoregional disease control and survival. In other words, even in the absence of certain conditions such as low serum Tg levels or after RAI therapy, periodic US would be omitted in long-term follow-up after TT in patients with PTC exhibiting low risk of recurrence. Among eight patients who underwent FNA in both groups, only one patient with locoregional recurrence in the PE group had an elevated serum Tg levels. In this study, serum Tg levels were of low value in determining whether locoregional recurrence was present. The ATA guidelines do not recommend postoperative RAI therapy for low- and most intermediate-risk patients with PTC [2]. Although prophylactic CND is optional in thyroidectomy [2], it is recommended in the Japanese guidelines [17]; therefore, CND was performed in all patients in our study cohort. This may account for the non-occurrence of clinically problematic recurrence, such as recurrent laryngeal nerve palsy in both cohorts, and may lead to an underestimation of the clinical significance of periodic US.
A high frequency of false-positive US findings may prompt additional testing or unnecessary additional interventions, resulting in increased costs and intervention-related complications. According to the 2024 medical fee list of the National Insurance System for Health in Japan, annual US costs extra 3,500 yen per patient, and if suspicious lesions were followed-up with repeat US at the physician’s discretion, the same additional cost will be incurred. A benign diagnosis by FNA for lesions with US abnormalities results in an additional cost of 4,500 yen. Furthermore, false-positive results can lead to unnecessary anxiety in patients with PTC. Patients with concerns about thyroid cancer recurrence, as well as patients with thyroid cancer recurrence, reported a significantly lower health-related quality of life than those without concerns about recurrence [18].
PE is performed regularly during postoperative surveillance, and face-to-face consultation and neck palpation by a specialist physician provide reassurance to patients and may improve mental well-being [19]. Although not all locoregional recurrences are palpable, detecting clinically asymptomatic local recurrences in patients with low- and intermediate-risk PTC may lead to “overdiagnosis,” which is a problem in cancer screening tests [20]. Although no study has evaluated the impact of adding periodic neck US to routine PE on locoregional control of patients with PTC, the structural neck recurrence rate in both groups in our study was similar to that of previous studies that detected recurrences performing periodic US in patients with low-risk PTC recurrence [13-15]. There were no significant differences in locoregional relapse-free survival rates between the PE and US groups. As an ancillary finding in this study, periodic US did not significantly affect survival, which was consistent with the previous retrospective study [21]. In addition, although the size of neck lymph nodes measured on US at the time of detecting locoregional recurrence tended to be larger in the PE group than in the US group, no complications occurred in the subsequent salvage surgery in either group. These findings showed that early detection of asymptomatic local recurrence using periodic US and immediate intervention did not significantly affect locoregional disease control. Therefore, the results of the present study would be extrapolated to answer the need for periodic US in postoperative surveillance of low- and intermediate-risk patients with PTC undergoing TT.
This study had a few limitations. First, this was a single-center study with a small sample size and retrospective design. Performing prospective two-arm studies is impractical because a large sample size and long follow-up period are required to confirm recurrence and thyroid cancer-specific survival, which have a good prognosis. Second, because our study included patients who underwent TT between 2000–2016, patients with a clinical stage that recommended lobectomy in the recent guidelines were also included [17]. However, we excluded patients with pT1aN0M0 PTC from our analysis and recognized that the results could not be applied to high-risk patients. Third, it was difficult to ensure that the method of follow-up was strictly the same between physicians because of a retrospective design. Furthermore, outpatient physicians sometimes changed during the follow-up period. For patients included in this study, postoperative surveillance, including neck US, was performed by a physician specializing in thyroid surgery; therefore, there was little influence on the surveillance evaluation. Finally, because structural neck recurrence was diagnosed using cytological analysis and/or Tg measurement using FNA, recurrences detected by WBS were not included. Consequently, the number of patients who experienced relapse may have been underestimated. However, in this study, WBS was not used to detect recurrence because none of the patients underwent postoperative RAI after matching by propensity score.
In conclusion, our findings revealed that the use of periodic neck US for postoperative surveillance of low- and intermediate-risk patients with PTC undergoing TT did not significantly affect locoregional disease control. Although the results obtained from this study do not completely deny the benefit of US, these would provide an opportunity to re-evaluate the usefulness and necessity of periodic US for patients with PTC with low risk of recurrence.
Acknowledgments
We would like to thank Editage (www.editage.com) for English language editing.
Disclosure
None of the authors have any potential conflicts of interest associated with this research.
Author Contributions
T.I. (Takahiro Inaishi) and T.K. conceived and designed the study. D.T., T.I. (Takahiro Ichikawa), and G.I. contributed to the acquisition of patient data. T.I. (Takahiro Inaishi) analyzed the data and wrote the manuscript. A.H., M.O., N.M., and T.K. contributed to the interpretation of the comprehensive data. D.T., T.I. (Takahiro Ichikawa), G.I., A.H., M.O., N.M., and T.K. critically reviewed important intellectual content and revised the manuscript. The final manuscript was read and approved by all authors.
Funding
This study received no funding.
References
- 1 Megwalu UC, Moon PK (2022) Thyroid cancer incidence and mortality trends in the United States: 2000–2018. Thyroid 32: 560–570.
- 2 Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, et al. (2016) 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid 26: 1–133.
- 3 Banerjee M, Muenz DG, Chang JT, Papaleontiou M, Haymart MR (2014) Tree-based model for thyroid cancer prognostication. J Clin Endocrinol Metab 99: 3737–3745.
- 4 Haber RS (2000) Role of ultrasonography in the diagnosis and management of thyroid cancer. Endocr Pract 6: 396–400.
- 5 Leenhardt L, Erdogan MF, Hegedus L, Mandel SJ, Paschke R, et al. (2013) 2013 European thyroid association guidelines for cervical ultrasound scan and ultrasound-guided techniques in the postoperative management of patients with thyroid cancer. Eur Thyroid J 2: 147–159.
- 6 Haymart MR, Banerjee M, Yang D, Stewart AK, Sisson JC, et al. (2013) Variation in the management of thyroid cancer. J Clin Endocrinol Metab 98: 2001–2008.
- 7 de Campos Lopes SG, Dias Silva Ferreira DN, Fernandes VAR, da Costa Cardoso Marques HM, da Silva Santos Pereira RF, et al. (2022) The role of neck ultrasound in the follow-up of low- and intermediate-risk papillary thyroid cancer. Arch Endocrinol Metab 66: 481–488.
- 8 Frasoldati A, Pesenti M, Gallo M, Caroggio A, Salvo D, et al. (2003) Diagnosis of neck recurrences in patients with differentiated thyroid carcinoma. Cancer 97: 90–96.
- 9 Gray JL, Singh G, Uttley L, Balasubramanian SP (2018) Routine thyroglobulin, neck ultrasound and physical examination in the routine follow up of patients with differentiated thyroid cancer-where is the evidence? Endocrine 62: 26–33.
- 10 Rosário PW, Tavares WC, Borges MA, Santos JB, Calsolari MR (2014) Ultrasonographic differentiation of cervical lymph nodes in patients with papillary thyroid carcinoma after thyroidectomy and radioiodine ablation: a prospective study. Endocr Pract 20: 293–298.
- 11 Kamaya A, Gross M, Akatsu H, Jeffrey RB (2011) Recurrence in the thyroidectomy bed: sonographic findings. AJR Am J Roentgenol 196: 66–70.
- 12 Wang LY, Roman BR, Palmer FL, Tuttle RM, Shaha AR, et al. (2016) Effectiveness of routine ultrasonographic surveillance of patients with low-risk papillary carcinoma of the thyroid. Surgery 159: 1390–1395.
- 13 Yang SP, Bach AM, Tuttle RM, Fish SA (2015) Serial neck ultrasound is more likely to identify false-positive abnormalities than clinically significant disease in low-risk papillary thyroid cancer patients. Endocr Pract 21: 1372–1379.
- 14 Peiling Yang S, Bach AM, Tuttle RM, Fish SA (2015) Frequent screening with serial neck ultrasound is more likely to identify false-positive abnormalities than clinically significant disease in the surveillance of intermediate risk papillary thyroid cancer patients without suspicious findings on follow-up ultrasound evaluation. J Clin Endocrinol Metab 100: 1561–1567.
- 15 Sek KS, Tsang I, Lee XY, Albaqmi OH, Morosan Allo YJ, et al. (2021) Frequent neck US in papillary thyroid cancer likely detects non-actionable findings. Clin Endocrinol (Oxf) 94: 504–512.
- 16 Rosario PW, Mourão GF, Calsolari MR (2019) Repeat ultrasonography in the first years after therapy with radioiodine is not necessary in most patients with papillary thyroid carcinoma when postoperative ultrasonography is negative: a reduction of costs and false-positives. Eur Thyroid J 8: 41–45.
- 17 Ito Y, Onoda N, Okamoto T (2020) The revised clinical practice guidelines on the management of thyroid tumors by the Japan Associations of Endocrine Surgeons: core questions and recommendations for treatments of thyroid cancer. Endocr J 67: 669–717.
- 18 Hedman C, Djärv T, Strang P, Lundgren CI (2016) Determinants of long-term quality of life in patients with differentiated thyroid carcinoma—a population-based cohort study in Sweden. Acta Oncol 55: 365–369.
- 19 Bender JL, Wiljer D, Sawka AM, Tsang R, Alkazaz N, et al. (2016) Thyroid cancer survivors’ perceptions of survivorship care follow-up options: a cross-sectional, mixed-methods survey. Support Care Cancer 24: 2007–2015.
- 20 Wegwarth O, Schwartz LM, Woloshin S, Gaissmaier W, Gigerenzer G (2012) Do physicians understand cancer screening statistics? a national survey of primary care physicians in the United States. Ann Intern Med 156: 340–349.
- 21 Banerjee M, Wiebel JL, Guo C, Gay B, Haymart MR (2016) Use of imaging tests after primary treatment of thyroid cancer in the United States: population based retrospective cohort study evaluating death and recurrence. BMJ 354: i3839.
