Papillary thyroid cancer (PTC) accounts for more than 90% of all thyroid neoplasms.^1,2 Most PTCs are associated with an indolent disease course and have a favorable prognosis even after low-intensity treatment. Therefore, disease management includes a wide range of options, from active surveillance to radical surgery and subsequent radioactive iodine (RAI) ablation.³ Consequently, the major clinical challenge is to stratify patients by risk of mortality or recurrence. At present, several clinicopathologic characteristics have been recognized as being associated with an unfavorable prognosis, including older age, large primary tumor size, extrathyroidal extension (ETE), lymph node metastasis (LNM), and distant metastasis.^3-6 Patients with these risk factors thus require aggressive treatment, whereas low-intensity treatment may be sufficient for patients who do not have these risk factors.^3,4,7

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.

Background: The value of serum thyroglobulin/antithyroglobulin (Tg/antithyroglobulin antibody [ATg]) for papillary thyroid carcinoma (PTC) surveillance after lobectomy was investigated. We aimed to examine the association between postlobectomy serum Tg/ATg and PTC structural recurrence and define applicable values for stratification. Methods: PTC patients who underwent lobectomy with adequate serum Tg/ATg data during 2000–2014 were selected. Predictive classifiers of recurrence using random forest were established combining different variables related to serum Tg (ATg-negative patients) or ATg (ATg-positive patients). Cutoff values were determined with receiver operating characteristic curves when applicable. Kaplan–Meier curve and Cox regression were performed to examine the predictive value of elevated Tg/ATg. Results: Of 1451 patients enrolled, 66 (6.3%) and 26 (6.5%) patients in the ATg-negative group ( n = 1050) and ATg-positive group ( n = 401) developed recurrence. The established classifier of serum Tg ( n = 1050) showed a favorable association with recurrence (AUC = 0.81), while serum ATg did not (AUC = 0.72). The optimal cutoff values of the first Tg (FTg, measured 6–12 months after lobectomy) and last Tg (LTg, measured most recently) were 5.3 and 11.0 ng/mL, respectively. Elevated LTg patients had significantly higher recurrence rates than normal LTg patients (23.5% vs. 4.4%, p < 0.05). Patients with elevated FTg had significantly lower recurrence-free survival rates than patients with normal FTg in all ATg-negative patients, low-risk patients, and intermediate- to high-risk patients (according to the American Thyroid Association initial risk stratification) ( n = 1050, 583, and 467, all p < 0.05). Multivariate analysis indicated patients with elevated FTg had twice the recurrent risk compared with those with normal FTg (hazard ratio = 2.052). Conclusions: Postlobectomy serum Tg has favorable value for predicting recurrence in PTC patients, and reasonable thresholds could identify patients at higher risk for recurrence during follow-up.

Membrane-associated ring-CH-type finger (MARCH) proteins belong to the E3 ubiquitin ligase family, which regulates protein stability by increasing ubiquitination. Recent evidence has shown that some MARCH proteins play important roles in cancer development. However, the role of MARCH6 in tumorigenesis, including thyroid tumorigenesis, remains unknown. In this study, we determined that MARCH6 was upregulated in the majority of primary papillary thyroid cancers (PTCs) at both the mRNA and protein levels. Gain-of-function and loss-of-function studies demonstrated that MARCH6 suppressed apoptosis and promoted cell cycle progression, cell proliferation, growth, migration and tumorigenesis in thyroid cancer cells. Mechanistically, MARCH6 interacted with and downregulated DHX9. Knockdown of DHX9 enhanced the proliferative and migratory abilities of thyroid cancer cells. The inhibitory effect of MARCH6 knockdown on thyroid cancer cell growth and migration was also reversed by DHX9 silencing. In addition, MARCH6 activated the AKT/mTOR signaling pathway in a manner dependent on the downregulation of DHX9. Overall, MARCH6 functions as a potential oncogene in thyroid cancer by destabilizing DHX9 and activating AKT/mTOR signaling.

Lobectomy is not advocated for papillary thyroid carcinoma (PTC) with high-risk features, although there is no high-level evidence showing that this is an inferior strategy. This study aimed to examine the association between the extent of surgery and survival of patients with PTC and high-risk features. Consecutive patients with PTC and at least one high-risk feature treated in 2000–2012 were included in the study. High-risk features were defined as: primary tumour larger than 4 cm, gross extrathyroidal extension, macroscopic multifocality, and confirmed nodal metastasis including pathological lateral neck metastasis (pN1b) or more than five central lymph node metastases. Cox proportional hazards models were employed to measure the association between the extent of surgery and disease-specific survival (DSS) in the whole cohort and in a matched-pair analysis. Among a total of 2059 patients with high-risk features, 1224 underwent lobectomy and 835 had total thyroidectomy. Patients who underwent total thyroidectomy had significantly higher rates of bilateral cancer than those who had a lobectomy (79.4 versus 2.7 per cent respectively), macroscopic multifocality (80.8 versus 32.8 per cent) and bilateral neck metastasis (30.9 versus 3.3 per cent) (all P < 0.001). With a median follow-up of 93 months, multivariable analysis showed that the extent of surgery was not associated with DSS in the whole cohort (hazard ratio 1.36, 95 per cent c.i. 0.75 to 2.48; P = 0.310). After 1 : 1 case–control matching of 528 patients, no significant difference between lobectomy and total thyroidectomy groups was observed with respect to the 10-year DSS rate (94.3 versus 95.2 per cent respectively; P = 0.323) or 10-year recurrence-free survival rate (75.8 versus 79.2 per cent; P = 0.784). Lobectomy was not associated with significantly worse outcomes for patients with PTC and high-risk features.