In the United States, the rate of TT for PTC increased every year from the years 2000 to 2014, and TT was more likely to be performed in patients with PTC with tumor sizes <4 cm;16 however, multiple studies have shown that TT did not contribute to reduced recurrence and survival benefits.11,12,13,14,17 Our study showed that the efficacy of lobectomy for RFS was comparable with that of TT (log-rank p = 0.80) (Fig. 2) in selected unilateral PTC with ipsilateral LLNM. Moreover, lobectomy could lower the rate of unsatisfactory TSH control.

Wang et al.12 and Song et al.11 reported equivalent RFS between lobectomy and TT in appropriately selected patients with unilateral PTC and LLNM; however, the condition of the contralateral lobe has not yet been reported. Dong et al.18 reported that the recurrence rate of PTC in the contralateral remnant thyroid tissue was 1.5% (7/466) over a median 18.4-year follow-up period. In our study, occasional minimal PTC was found in the contralateral lobe in approximately 18.8% of patients (18/96) in the TT group. Only 2.9% of patients (3/102) in the lobectomy group had reoperations for confirmed PTC in the contralateral lobe, which is consistent with the study by Dong et al.18 Although our follow-up period was relatively short, it covered the peak time of recurrence (1–3 years) of PTC, as reported in previous literature.19,20,21,22,23 Therefore, we concluded that lobectomy did not increase the risk of reoperation of the contralateral lobe within a relatively short follow-up period. It should be noted that minimal PTC was detected in approximately 54.5% of patients (6/11) in the TT group who had TIRADS 4a nodules in the contralateral lobe; therefore, TT should be recommended to these patients to reduce possible recurrence.

It was reported that ETE was an important risk factor for recurrence in patients with LLNM.22,24 Although 6% of patients in the lobectomy group exhibited ETE, the multicenter study by Kuba et al.25 reported that the 10-year RFS after TT was comparable with that after lobectomy. Our study included 13.7% of patients with ETE in the lobectomy group, and we found no significant difference in RFS between the lobectomy and TT groups. Evidence has also shown that there are no differences in overall survival (OS) or disease-specific survival after TT or lobectomy, even in patients who had undergone lobectomy accompanied by high-risk factors, including ETE.14,17 Thus, lobectomy may be an alternative strategy for patients with unilateral PTC and LLNM carrying high-risk factors such as RLN invasion.

There is no doubt that lobectomy is better tolerated than TT, particularly for parathyroid protection. Kuba et al.25 reported that the incidence rates of transient and permanent hypocalcemia after TT were 38% and 8%, respectively, a result that was similar to that reported by Song et al. (43.3% and 4.5%, respectively).11 In our study, the incidence of transient and permanent hypocalcemia in the TT group was 11.5% and 1.0%, respectively. Due to the exclusion of PTC with ETE, no permanent RLN injury occurred in the studies by Song et al.11 and Wang et al.12 Kuba et al.25 reported that the incidence of RLN paralysis over a 1-year period was not significantly different between the TT and lobectomy groups (7.5% vs. 2.5%; p = 0.203). In our study, the incidence rates of permanent RLN injury in the lobectomy and TT groups were 5.9% and 9.4% respectively; however, approximately 93.3% of RLN injuries (14/15) were due to tumor invasion, and in these patients, the RLN was excised to achieve R0 resection. Given the similar rates of RFS between the two groups in our study, lobectomy was considered an alternative option when the RLN was invaded. This approach could reduce the risk of tracheotomy caused by bilateral RLN injury.

RAI therapy is usually recommended for patients with LLNM after TT and could contribute to recurrence detection using Tg; however, there is evidence showing that it did not improve RFS and OS.8,9,10,11,12,25 In our study, the recurrence rate for patients who received RAI treatment was comparable with that of patients who did not receive RAI treatment in the TT group (5.3% vs. 4.8%; p = 1.000). In order to fully explore the benefits of RAI treatment following TT, patients who did not receive RAI treatment in the TT group were excluded (ESM Table 3). However, in our cohort, we did not observe a significant improvement in RFS as a result of RAI therapy following TT (ESM Fig. 1). Thus, RAI therapy should not be the definitive reason for performing TT in some patients with unilateral PTC and ipsilateral LLNM.

Exogenous L-T4 intake for TSH suppression is an important postoperative therapy for patients with PTC; however, TSH suppression could increase the risk of coronary heart disease, ischemic stroke, reduced bone mineral density, and osteoporotic fractures,15,26,27 which are closely related to the dose of L-T4. Wang et al.12 reported that compared with TT, lobectomy in properly selected PTC with LLNM could significantly reduce the intake dose of L-T4. Thus, cardiovascular changes, especially an increased resting heart rate, were significantly reduced in patients who had undergone lobectomy. A multicenter prospective study that included 2013 patients with differentiated thyroid cancer indicated that 1236 patients (61.4%) achieved targeted values of TSH suppression at 1 year after surgery.28 A prospective study by Chen et al.29 showed that the incidence of well-controlled TSH levels 1 year after lobectomy was significantly higher than that after TT. Our study showed a lower rate of unsatisfactory TSH control in patients who had undergone lobectomy. Therefore, lobectomy could reduce anxiety caused by unsatisfactory TSH control and the potential risk of cardiovascular disease and osteoporotic fractures.

Our study had several limitations. First, the follow-up duration in our study was relatively short; therefore, a study with a longer time period is needed to further illustrate the outcome of lobectomy in unilateral N1b PTC. Second, the benefit to the cardiovascular and skeletal organs was not evaluated because of the lack of related data collection. Third, although the candidates for lobectomy were carefully selected by a multidisciplinary team before surgery based on strict enrollment criteria, there was a selection bias among patients in the lobectomy group, which may be due to the influence of the consulting surgeons. Thus, a multicenter, randomized, prospective study is needed to further illustrate the oncological safety of lobectomy in these patients.