This cohort study investigates the association between lobectomy vs total thyroidectomy and outcomes in patients with intermediate-risk papillary thyroid cancer and lymph node metastasis.
Key Points
Question
Is lobectomy associated with a significantly worse outcome compared with total thyroidectomy (TT) in patients with intermediate-risk papillary thyroid cancer and lymph node metastasis?
Findings
In this cohort study of 946 patients, after propensity score matching for potential prognostic factors, 265 pairs of patients were available for analysis. The 5-year recurrent-free survival rates were 92.3% and 93.7% for patients in the lobectomy group and TT group, respectively.
Meaning
Results suggest that patients with intermediate-risk papillary thyroid cancer and lymph node metastasis had a similar recurrent-free survival after lobectomy vs TT.
Abstract
Importance
Surgical treatment of patients with papillary thyroid cancer (PTC) by either lobectomy or total thyroidectomy (TT) has long been a topic of debate, especially for patients with intermediate-risk PTC.
Objective
To compare recurrence-free survival (RFS) for patients with PTC and lymph node metastasis after lobectomy vs TT.
Design, Setting, and Participants
This retrospective cohort study included a review of patients with PTC treated from January 1, 2000, to December 31, 2017. Propensity score matching (PSM) was performed between patients treated with lobectomy and TT. This study involved a single institute in a cancer referral center. Enrolled were adult patients (aged 18-75 years) with unilateral PTC and ipsilateral clinical lateral neck metastasis (cN1b). Patients with the following characteristics were excluded: a lymph node yield less than 20, primary tumor size greater than 4 cm, gross extrathyroidal extension, metastatic lymph node size greater than 3 cm, and distant metastasis. Data analysis was performed from April 1 to April 30, 2022.
Exposures
Lobectomy and TT.
Main Outcomes and Measures
The primary outcome was the association between extent of surgery and RFS, assessed using Cox proportional hazards regression models.
Results
A total of 946 patients with PTC (mean [SD] age, 37.0 [12.1] years, 630 female individuals [66.6%]) were analyzed. Lobectomy (624 [66.0%]) was negatively correlated with the frequencies of older age (≥65 years, 17 [2.7%]), female sex (393 [63.0%]), multifocality (132 [21.2%]), minor extrathyroidal extension (259 [41.5%]), number of metastatic lymph nodes (median [range], 9 [6-14] nodes), and radioactive iodine ablation (0). After PSM with treatment period and potential prognostic factors (age, sex, primary tumor size, multifocality, minor extrathyroidal extension, number of lymph node metastases and lymph node ratio), 265 pairs of patients were available for analysis. After a median (range) follow-up of 60 (9-150) months in the lobectomy group and 58 (8-161) months in the TT group, 21 (7.9%) and 17 (6.4%) structural recurrences were identified in the lobectomy and TT groups, respectively. Lobectomy was not associated with significantly compromised 5-year RFS rate (lobectomy, 92.3% vs TT, 93.7%; adjusted hazard ratio, 1.10; 95% CI, 0.58-2.11; P = .77). Power analysis indicated that the test had 90% power to detect a more than 4.9% RFS difference. No significant difference in RFS was observed between patients treated with TT and radioactive iodine ablation (n = 75) and their counterparts (adjusted hazard ratio, 0.59; 95% CI, 0.14-2.41; P = .46).
Conclusions and Relevance
Results of this cohort study suggest that patients with PTC and lymph node metastasis had a similar RFS after lobectomy vs those who had TT. If radioactive iodine ablation is not going to be performed, lobectomy may be an effective alternative option.
Introduction
Papillary thyroid cancer (PTC) accounts for more than 90% of all thyroid neoplasms and is commonly associated with an indolent disease course and good prognosis.1,2,3 With increasing emphasis on risk-stratified management, guideline-recommended approaches have evolved to allow for low-intensity treatment options in low-risk patients.4,5 These patients are usually defined as those with intrathyroidal and localized lesions. A predominant change in patient treatment is the decreased use of total thyroidectomy (TT) and postsurgical radioactive iodine (RAI) ablation.4,6
Regarding patients with PTC and lymph node metastasis, although direct evidence is lacking, TT and subsequent RAI ablation are still considered management options according to the guidelines.4 The therapeutic strategy is recommended to conform with the relatively higher recurrence risk in patients with lymph node metastasis, especially those with clinically positive nodes (cN+). However, the superiority of TT over lobectomy for these patients is actually unclear. First, lymph node metastasis is not considered a predominant risk factor for disease-specific mortality in major staging systems (eg, TNM, MAGES staging system).7,8 Second, inconsistent data always exist for the effect of TT and subsequent RAI ablation on decreasing tumor recurrence.9,10
A previous study based on our single-institute cohort has indicated that even in patients with extrathyroidal or nodal disease, lobectomy may not be associated with significantly higher thyroid cancer-related mortality or recurrence.11 Then, the present study was carried out to compare recurrence-free survival (RFS) of patients with intermediate-risk PTC and lymph node metastasis treated with lobectomy vs TT using propensity score–matching (PSM) analysis.
Methods
This retrospective cohort study was performed with untreated adult patients (aged 18-75 years) who underwent surgery for PTC at the Chinese Academy of Medical Sciences, Cancer Hospital, from January 1, 2000, to December 31, 2017. The study was approved by the Ethics Committee of the Cancer Hospital, Chinese Academy of Medical Sciences. Informed consent was obtained at the time of surgery for the general use of clinical information for future studies. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines.
The inclusion criteria were patients with PTC and clinical ipsilateral positive lymph nodes identified on the lateral neck (cN1b) and sufficient follow-up data (more than 24 months). Patients with evidence of a contralateral lesion (primary or central lymph node), primary tumor size greater than 4 cm or gross extrathyroidal extension (gETE; stages T3-T4), metastatic lymph node size greater than 3 cm, inadequate lymph node yield (total harvested lymph nodes <20), distant metastasis (stage M1), second primary malignancies, or incomplete resection were excluded. Patients with aggressive histologic variants were also excluded. Patients who underwent lobectomy and TT were categorized into study and control groups, respectively.
Variables such as patient age, sex, tumor characteristics, and treatment modalities were obtained from the medical records. cN1b was defined as any metastatic lymph nodes in the lateral neck identified by palpation or imaging (ultrasonography or computed tomography) and confirmed with cytology or frozen section preoperatively or intraoperatively. The lobectomy group included patients who underwent lobectomy with or without isthmectomy, and patients who underwent lobectomy with nodule enucleation were also included in the lobectomy group. The TT group included patients who underwent total, subtotal, or near-total thyroid resection.
Postoperative treatments included conventional thyrotropin suppression at appropriate levels and RAI ablation. Physical examinations, neck ultrasonography, and computed tomography or chest radiography were performed regularly every 6 months within the first 5 years and every 12 months thereafter. The primary end point of the study was structural recurrence, which was determined by the medical records in combination with telephone follow-up. Regional or local recurrences were proven by either cytology or pathology, whereas distant metastasis was determined by computed tomography or emission computed tomography. RFS was calculated from the time of surgery for PTC to structural recurrence. Thyroid function tests, including thyroglobulin and thyroglobulin antibodies, were routinely measured during follow-up, and biochemical abnormalities alone were not recorded as recurrence.
For the reliability and comparability of the lobectomy and TT groups, propensity score analysis with 1:1 matching was used to balance variables (treatment period and potential prognostic factors for prognosis recorded in our database and based on prior literatures: age, sex, primary tumor size, minor extrathyroidal extension [mETE], multifocality, number of lymph node metastases, and lymph node ratio [LNR]). Age cutoffs from 45 years to 65 years in 10-year intervals were examined. The treatment period was considered as 1 variable in the analysis and was treated as a binomial categorical variable. Primary tumor size was divided into 3 groups: 1 cm or smaller, 1 to 2 cm, and larger than 2 cm. All lymph node–related variables included both central and lateral lymph node data. The LNR was defined as the number of metastatic lymph nodes per number of harvested lymph nodes. The number of metastatic lymph nodes and LNR were considered continuous variables. Tumor stage and initial risk stratification were performed according to the American Joint Committee on Cancer staging system (8th edition) and 2015 American Thyroid Association (ATA) guidelines.
Statistical Analysis
The sample size of the study was reflective of patients meeting eligibility criteria based on their histologic diagnosis and year of treatment. Summary statistics were provided as whole numbers and percentages for categorical variables and medians with IQR for continuous variables. The distribution of categorical variables was tested using Pearson χ2 test or Fisher exact test, as appropriate. The distribution of continuous variables was tested using the t test (normal distribution) or Wilcoxon rank sum test (abnormal distribution), respectively. Then, PSM analysis was used to account for differences in baseline patient characteristics between the 2 groups. This score was calculated using a logistic regression model with the extent of surgery as the outcome and treatment period and potential prognostic factors recorded in our database (age, sex, primary tumor size, mETE, multifocality, number of lymph node metastases, and LNR) as determinants. This predicted probability was used as a score for 1:1 case matching with the nearest neighbor approach with a tolerance of 0.02. After matching, estimates of RFS proportions were computed using the Kaplan-Meier method, and survival distributions were compared across groups using the log-rank test. Univariate and multivariate Cox proportional hazards models were used to identify potential prognostic factors for RFS (multicollinearity of factors was examined using correlation coefficient), and backward selection was performed. Adjusted survival curves were created based on multivariate Cox proportional-hazards model and focused on the study factor (lobectomy vs TT). Significance levels were interpreted as 2-sided P < .05. Finally, we performed a power analysis using PASS 15, version 15.0.5 (NCSS), with regard to our ability to detect a difference in RFS between the 2 groups. All statistical analyses were performed using IBM SPSS software, version 26.0 (IBM Corp). Data analysis was performed from April 1 to April 30, 2022.
Results
Baseline Characteristics Before and After Propensity Score Matching
A total of 2228 patients with unilateral cN1b PTC were identified in the studied period. After exclusion of patients with a contralateral lesion (primary or central lymph node) (n = 825); primary tumor size greater than 4 cm or gETE (n = 286); metastatic lymph node greater than 3 cm (n = 8); insufficient lymph node yield (n = 94); distant metastasis, second primary malignancies, or incompletely resected tumors (n = 41); and aggressive histologic variants (n = 28), 946 patients (mean [SD] age, 37.0 [12.1] years; 630 female individuals [66.6%]; 316 male individuals [33.4%]; 624 lobectomy group [66.0%]; 322 TT group [34.0%]) met the inclusion criteria (Figure 1).
Figure 1. Flowchart of Patient Inclusion and Exclusion.
Enrolled were adult patients with unilateral papillary thyroid cancer (PTC) and ipsilateral clinical lateral neck metastasis (cN1b). gETE indicates gross extrathyroidal extension.
Compared with patients who underwent TT, patients treated with lobectomy were more likely to be male (231 [37.0%] vs 85 [26.4%]; relative risk [RR], 0.85; 95% CI, 0.77-0.94), younger (≥65 years, 17 [2.7%] vs 10 [3.1%]; RR, 0.93; 95% CI, 0.59-1.44), have less multifocality (132 [21.2%] vs 107 [33.2%]; RR, 0.79; 95% CI, 0.70-0.89), less mETE (259 [41.5%] vs 204 [63.4%]; RR, 0.74; 95% CI, 0.67-0.81), and more metastatic lymph nodes (median [range], 9 [6-14] nodes vs 8 [5-12] nodes). Moreover, the proportion of TT increased over time, which was more than lobectomy between 2013 and 2017 (239 cases vs 220 cases) (Table 1). Lobectomy was negatively correlated with female sex (393 [63.0%]) and radioactive iodine ablation (0).
Table 1. Patient Demographic, Clinical, and Pathologic Characteristics by Extent of Surgery, 2000-2017 (N = 946).
| Characteristics | No. (%) | RR (95%CI) | ||
|---|---|---|---|---|
| Overall | Lobectomy | Total thyroidectomy | ||
| No. | 946 | 624 | 322 | |
| Sex | ||||
| Female | 630 (66.6) | 393 (63.0) | 237 (73.6) | 1 [Reference] |
| Male | 316 (33.4) | 231 (37.0) | 85 (26.4) | 0.85 (0.77-0.94) |
| Age, y | ||||
| <45 | 645 (68.2) | 439 (70.4) | 206 (64.0) | 1 [Reference] |
| 45-55 | 192 (20.3) | 125 (20.0) | 67 (20.8) | 0.96 (0.84-1.09) |
| 55-65 | 82 (8.7) | 43 (6.9) | 39 (12.1) | 0.77 (0.64-0.93) |
| ≥65 | 27 (2.9) | 17 (2.7) | 10 (3.1) | 0.93 (0.59-1.44) |
| Treatment period | ||||
| 2000-2012 | 487 (51.5) | 404 (64.7) | 83 (25.8) | 1 [Reference] |
| 2013-2017 | 459 (48.5) | 220 (35.3) | 239 (74.2) | 0.58 (0.53-0.64) |
| Primary tumor size, cm | ||||
| ≤1 | 360 (38.1) | 234 (37.5) | 126 (39.1) | 1 [Reference] |
| 1-2 | 401 (42.4) | 266 (42.6) | 135 (41.9) | 1.02 (0.9-1.16) |
| >2 | 185 (19.6) | 124 (19.9) | 61 (18.9) | 1.03 (0.88-1.21) |
| Multifocality | 239 (25.3) | 132 (21.2) | 107 (33.2) | 0.79 (0.70-0.89) |
| Minor extrathyroidal extension | 463 (48.9) | 259 (41.5) | 204 (63.4) | 0.74 (0.67-0.81) |
| No. of metastatic lymph nodes, median (IQR) | 8 (5-13) | 9 (6-14) | 8 (5-12) | NA |
| Lymph node ratio, median (IQR) | 0.2 (01-0.3) | 0.2 (0.1-0.3) | 0.2 (0.1-0.3) | NA |
Abbreviations: NA, not applicable; RR, relative risk.
After PSM with treatment period and potential prognostic factors (age, sex, primary tumor size, multifocality, mETE, number of lymph node metastases, and LNR), 265 pairs of patients were available for analysis (Figure 1). Compared with patients in the TT group, patients in the lobectomy group were more likely to be female (192 [72.5%] vs 185 [69.8%]; RR, 0.94; 95% CI, 0.76-1.16), slightly older (≥65 years, 6 [2.3%] vs 4 [1.5%]; RR, 0.79; 95% CI, 0.21-2.96), in the early treatment period (2000-2012, 89 [33.6%] vs 83 [31.3%]; RR, 1.05; 95% CI, 0.85-1.29), have a larger tumor (>2 cm, 52 [19.6%] vs 48 [18.1%]; RR, 0.91; 95% CI, 0.69-1.22), and have less multifocality (74 [27.9%] vs 90 [34.0%]; RR, 1.15; 95% CI, 0.95-1.40). Similar numbers of metastatic lymph nodes (median [IQR], 9 [5-13] nodes) and LNR (median [IQR], 0.2 [0.1-0.3]) were observed between 2 groups; however, none of these differences was significant (Table 2).
Table 2. Patient Demographic, Clinical, and Pathologic Characteristics by Extent of Surgery After PSM, 2000-2017 (N = 265 Pairs).
| Characteristics | No. (%) | RR (95%CI) | ||
|---|---|---|---|---|
| Overall | Lobectomy | Total thyroidectomy | ||
| No. | 530 | 265 | 265 | |
| Sex | ||||
| Female | 377 (71.1) | 192 (72.5) | 185 (69.8) | 1 [Reference] |
| Male | 153 (28.9) | 73 (27.5) | 80 (30.2) | 0.94 (0.76-1.16) |
| Age, y | ||||
| <45 | 376 (70.9) | 185 (69.8) | 191 (72.1) | 1 [Reference] |
| 45-55 | 106 (20.0) | 54 (20.4) | 52 (19.6) | 0.97 (0.69-1.34) |
| 55-65 | 38 (7.2) | 20 (7.5) | 18 (6.8) | 0.93 (0.52-1.68) |
| ≥65 | 10 (1.9) | 6 (2.3) | 4 (1.5) | 0.79 (0.21-2.96) |
| Treatment period | ||||
| 2000-2012 | 172 (32.5) | 89 (33.6) | 83 (31.3) | 1 [Reference] |
| 2013-2017 | 358 (67.5) | 176 (66.4) | 182 (68.7) | 1.05 (0.85-1.29) |
| Primary tumor size, cm | ||||
| ≤1 | 202 (38.1) | 96 (36.2) | 106 (40.0) | 1 [Reference] |
| 1-2 | 228 (43.0) | 117 (44.2) | 111 (43.7) | 0.93 (0.75-1.15) |
| >2 | 100 (18.9) | 52 (19.6) | 48 (18.1) | 0.91 (0.69-1.22) |
| Multifocality | 164 (30.9) | 74 (27.9) | 90 (34.0) | 1.15 (0.95-1.40) |
| Minor extrathyroidal extension | 312 (58.9) | 156 (58.9) | 156 (58.9) | 1 [Reference] |
| No. of metastatic lymph nodes, median (IQR) | 9 (5-13) | 9 (5-13) | 9 (5-13) | NA |
| Lymph node ratio, median (IQR) | 0.2 (0.1-0.3) | 0.2 (0.1-0.3) | 0.2 (0.1-0.3) | NA |
Abbreviations: NA, not applicable; PSM, propensity score matching; RR, relative risk.
Survival Analysis After PSM
After a median follow-up of 60 (9-150) months and 58 (8-161) months, 21 (7.9%) and 17 (6.4%) structural recurrences were identified in the lobectomy group and TT group, respectively. In the lobectomy group, 8, 18, and 3 recurrences were identified in the residual lobe, regional lymph nodes, and distant metastases, respectively. In the TT group, 16 and 2 recurrences were identified in regional lymph node and distant metastases, respectively. The 5-year RFS rates were 92.3% and 93.7% for the lobectomy group and TT groups, respectively (lobectomy unadjusted HR, 1.17; 95% CI, 0.62-2.22; P = .63) (Figure 2A). The number of lymph node metastases and LNR were multicollinearities, and LNR was excluded from multivariate analysis. Independent risk factors for decreased RFS in patients with unilateral cN1b PTC after lobectomy or TT were age (45-55 years: HR, 1.99; 95% CI, 0.96-4.14; P = .06; 55-65 years: HR, 2.34; 95% CI, 0.78-7.00; P = .13; ≥65 years: HR, 5.01; 95% CI, 1.14-22.04; P = .03) and numbers of metastatic lymph nodes (HR, 1.09; 95% CI, 1.05-1.13; P < .001) (Table 3). The HR of lobectomy vs TT after adjustment for age and number of lymph node metastases was 1.10 (95% CI, 0.58-2.11; P = .77) (Table 3 and Figure 2B). Stratified analysis was performed in patients treated with RAI ablation in the TT group (n = 75) and counterparts in the lobectomy group (n = 75), and no significant difference in RFS between the lobectomy and TT plus RAI ablation groups was found (5-year RFS rate, 94.3% vs 92.7%; lobectomy unadjusted HR, 0.74; 95% CI, 0.20-2.76; P = .65; lobectomy adjusted HR, 0.59; 95% CI, 0.14-2.41; P = .46) (Figure 2C-D). The power analysis was performed with 90% statistical power, 5% type I error, and 5-year RFS rate of TT group of 93.7%. It is estimated that a survival difference of 4.9% can be detected in the PSM cohort.
Figure 2. Recurrence-Free Survival of the Enrolled Patients After Propensity Score Matching.
A, Unadjusted recurrence-free survival. B, Recurrence-free survival after adjusting for other prognostic factors. C, Unadjusted recurrence-free survival in the total thyroidectomy (TT) plus radioactive iodine (RAI) ablation group and its counterparts. D, Recurrence-free survival in the TT plus RAI ablation group and its counterparts after adjusting for other prognostic factors.
Table 3. Univariable and Multivariable Survival Analysis.
| Characteristics | Univariable | Multivariable | ||
|---|---|---|---|---|
| HR (95%CI) | P value | HR (95%CI) | P value | |
| Sex | ||||
| Female | 1 [Reference] | NA | NA | NA |
| Male | 0.66 (0.34-1.30) | .23 | NA | NA |
| Age, y | ||||
| <45 | 1 [Reference] | NA | 1 [Reference] | NA |
| 45-55 | 1.94 (0.92-4.11) | .08 | 1.99 (0.96-4.14) | .06 |
| 55-65 | 2.42 (0.78-7.53) | .13 | 2.34 (0.78-7.00) | .13 |
| ≥65 | 5.03 (1.14-22.32) | .03 | 5.01 (1.14-22.04) | .03 |
| Extent of surgery | ||||
| Total thyroidectomy | 1 [Reference] | NA | 1 [Reference] | NA |
| Lobectomy | 1.21 (0.63-2.34) | .57 | 1.10 (0.58-2.11) | .77 |
| Primary tumor size, cm | ||||
| ≤1 | 1 [Reference] | NA | NA | NA |
| 1-2 | 1.18 (0.52-2.69) | .70 | NA | NA |
| >2 | 1.65 (0.68-4.02) | .27 | NA | NA |
| Multifocality | 1.06 (0.51-2.19) | .88 | NA | NA |
| Minor extrathyroidal extension | 1.06 (0.51-2.19) | .76 | NA | NA |
| No. of metastatic lymph nodes | 1.05 (1.00-1.12) | .07 | 1.09 (1.05-1.13) | <.001 |
| Lymph node ratio | 7.61 (0.29-202.77) | .23 | NA | NA |
Abbreviations: HR, hazard ratio; NA, not applicable.
Discussion
In the present cohort study, we compared RFS for patients with intermediate risk of PTC and lymph node metastasis after lobectomy vs TT. To create a comparable case series, we admitted patients with unilateral PTC with ipsilateral lateral neck metastasis, which ensured a similar tumor stage and surgical extent (except for the contralateral lobe of the thyroid). Moreover, PSM analysis was performed to minimize the influence of related factors. Results suggest that lobectomy had a similar RFS compared with TT in both unadjusted and adjusted analyses, and power analysis indicated that the study had 90% power to detect a more than 4.9% RFS difference. Given the lower complication rate of lobectomy, a maximal 4.9% RFS difference is acceptable, which enhances the reliability of the study results. Our findings call into question whether cN1b alone should be an absolute determinant for deciding the optimal extent of thyroid surgery for PTC.
Proponents of TT argue that complete resection of thyroid tissue mainly affords the opportunity to use RAI ablation for postoperative detection of residual or metastatic disease, as well as for treatment. Although the current ATA guidelines suggest that RAI ablation should be considered after TT in patients with intermediate-risk PTC, there are few and controversial data to make firm recommendations for them.4,9 Multivariate adjusted analyses from the Surveillance, Epidemiology, and End Results (SEER) Program suggest that RAI ablation is associated with a 29% reduction in the risk of death, with a hazard risk of 0.75 in patients with intermediate-risk PTC.12 However, a single-center retrospective study from Memorial Sloan-Kettering Cancer Center examining RFS suggested no significant benefit in patients with PTC treated with RAI ablation.13 Although 71% of patients in the TT group in our study did not receive RAI ablation, which might have potentially influenced the survival results, we think the 2 groups are comparable based on the conflicting results of the previously mentioned studies.12,13 Moreover, when we performed further stratified analyses in patients treated with TT plus RAI ablation and their counterparts, no significant difference was found, which conformed with result from the whole cohort. Certainly, the stratified comparison did not have enough power to examine the effect of RAI ablation on tumor recurrence subject to the limitation of sample size and case selection. Further study is needed on this topic.
It is generally accepted that lobectomy is only an optimal option for patients with low-risk PTC but not for patients with intermediate-high–risk PTC.4 In our previous reports, no advantages of TT over lobectomy for intermediate-risk PTC were found with respect to RFS or disease-specific survival rate, which may not be entirely surprising because similar findings have been obtained in several previous studies.14 A study by Matsuura et al15 analyzed 3756 patients with low-intermediate–risk node-negative thyroid cancer and showed no significant differences between lobectomy and TT for RFS (10-year RFS, 99.5% vs 98.3; P = .08) after PSM for age, sex, histology, pT stage, RAI ablation, and ATA initial risk stratification. Adam et al16 evaluated the National Cancer Database data of 61 775 patients with PTC, including 8%, 25%, and 1% of cases involving ETE, TNM, and distant metastasis, respectively, and showed that the extent of surgery was not independently associated with compromised survival. However, Suman et al17 reported that patients with cN1, lymphovascular invasion, ETE, positive margins, poorly differentiated PTC, and M1 disease in the TT group maintained a survival advantage compared with those in the lobectomy group after PSM (5 years: 96.5% vs 94.7% and 10 years: 90.9% vs 88.5%, respectively, P = .03). Several studies have reported similar findings, even for papillary thyroid microcarcinoma.18,19 The differences could be due to several factors, including inclusion and exclusion criteria, differences between the 2 groups, the criteria used to define disease recurrence, and possibly statistical methods.
Strengths and Limitations
Our study has several strengths. Due to the past treatment modality in the authors’ institute, a relatively large proportion of patients underwent lobectomy, which enabled this comparison. Although the criterion standard methodology to address this question is to carry out a randomized prospective clinical trial, the implementation is challenging owing to the low mortality rate of PTC. The largest cohort to date of patients with cN1b PTC in our study gave us the ability to perform PSM for well-known prognostic factors in PTC, such as age, primary tumor size, multifocality, mETE, number of lymph node metastases, and LNR, to minimize the effect of bias and show that TT was not associated with improved RFS.
Nevertheless, our study has several limitations. First, as this is a single-institutional study, several specific management factors existed, eg, a lower rate of RAI ablation use and a lower recurrence rate, may influence the results and may restrict the universality of the conclusion. Second, other than recurrence, survival outcome is another concern for this topic, but it was not analyzed in our study due to its low incidence rate (2 of 530 [0.4%]). Third, owing to the retrospective nature of these data, some characteristics (such as BRAF status, vascular invasion, extranodal extension and different surgeons) were not taken into consideration, which may have influenced the final results. Moreover, the sample size, performance of extent of surgery and RAI ablation, and the power analysis was not preplanned, which did have limited performance to evaluate. Further prospective study is needed but our study provides sound theoretical basis.
Conclusions
In conclusion, results of this cohort study suggest that patients with cN1b PTC who underwent lobectomy exhibited RFS rates similar to those who underwent TT after controlling for major prognostic factors. These findings suggest that cN1b alone should not be an absolute indication for TT. If RAI ablation is not going to be performed, lobectomy may be an effective alternative option for properly selected patients to optimize quality of life.
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