Our study is the first to explore the effectiveness and safety of RFA as a treatment modality for PTMC located adjacent to the trachea. We have compared the clinical outcomes of PTMCs with trachea-adjacent location and trachea-distant location, respectively. Technical success in our study was 100%, and the complication rate was less than 1%. During a mean follow-up period of 30.0 ± 16.5 months, we found no significant differences in volume, VRR, tumor disappearance rate, or disease progression rate between PTMCs with trachea-adjacent location and trachea-distant location. The trachea-adjacent location was not associated with disease progression in univariate and multivariate Cox regression analyses. Our study has revealed the effectiveness and safety of RFA as a treatment modality for PTMC located adjacent to the trachea.
Statements on the optimum management strategy for low-risk PTMC remain controversial. The currently available management strategies for low-risk PTMC include surgical resection, thermal ablation, and active surveillance, and each strategy has pros and cons (Chou et al. 2022; H.J. Kim, Cho, and Baek 2021; Sun et al. 2022). RFA, as a form of thermal ablation, is becoming an increasingly attractive option, especially for patients unsuitable for or reluctant to surgical resection and patients with great anxiety about AS (Choi and Jung 2020; Xue, Teng, and Wang 2022). Many studies investigating RFA for the treatment of PTC obtained promising outcomes(Yan et al. 2022; Zhang et al. 2020; Cho et al. 2020; Cao et al. 2021). In a recent meta-analysis, the VRR and tumor disappearance rate for PTMC at 12 months after RFA were 93.3% and 64%; the incidence of residual cancer, new thyroid cancer, and LNM after RFA were 0.3%, 2.5%, and 1.0%, respectively(Xue, Teng, and Wang 2022). In the current study, we explored a total of 1001 patients with solitary PTMC who underwent RFA with a follow-up time of 30.0 ± 16.5 months. The VRR, tumor disappearance rate, and disease progression rate for PTMC were respectively 99.0%, 87.5%, and 3.3%. These findings were in line with previous studies(Yan, Lan, et al. 2021; Wei et al. 2022; Xue, Teng, and Wang 2022; Cho et al. 2021), which further strengthens the argument that RFA could be an effective treatment option for low-risk PTMC.
Some researchers have questioned the feasibility of RFA for PTMCs adjacent to the trachea, stating the possibility of minimal ETE and an elevated risk of disease progression in tumors touching the medial capsular surrounding the trachea. However, the eighth edition of the AJCC guideline has exclued minimal ETE from the T stage classification due to little evidence of its impact on disease-related mortality and persistence/recurrence prediction in PTC (Tam et al. 2018; Tuttle, Haugen, and Perrier 2017). A prior study by Song et al. assessed the effectiveness of RFA for PTMC in the isthmus and reported a 100% tumor disappearance rate, with 0% incidence of LNM and 0.8% residual cancer, suggesting that RFA is an effective treatment option for PTMC in the isthmus (Song et al. 2020). Following that, Song et al. compared the clinical outcomes of RFA with total thyroidectomy for PTMCs in the isthmus, revealing that RFA can match total thyroidectomy in terms of treatment efficacy (Song et al. 2021). More recently, a prospective study by Zheng et al. focused on ablation for PTC with sonographic minimal ETE. The study demonstrated that ablation is similarly effective as surgery for T1N0M0 PTC cases with sonographic minimal ETE (Zheng, Dou, Liu, et al. 2023). However, to date, no study has explored the outcomes of TA for PTMCs adjacent to the trachea. In this study, we compared the efficacy of RFA for PTMCs with trachea-adjacent and trachea-distant locations after controlling for confounding factors using PSM. The tumor disappearance rate and VRR for PTMCs adjacent to the trachea were 87.6% and 99.5%, respectively, showing no significant differences from PTMCs distant from the trachea. Additionally, no significant differences could be observed in the incidence of new cancer, residual cancer, or LNM between PTMCs with trachea-adjacent and trachea-distant locations. The Kaplan-Meier analysis further revealed no significant differences in progression-free survival between PTMCs abutting the trachea and PTMCs distant from the trachea. We analyzed whether trachea-adjacent location was a risk factor affecting disease progression using univariable and multivariable analysis based on the Cox proportional hazards regression model, and no evidence was found to indicate that trachea-adjacent location influences disease progression. These results indicate that RFA is an effective treatment for ineligible patients with low-risk PTMC adjacent to the trachea.
The overall incidence of complications in the study was found to be 0.5%, which was lower than previous reported rates (2.0–3.6%) (van Dijk et al. 2022; Choi and Jung 2020; Cho et al. 2021). There was no statistically significant difference in complication incidence between PTMC adjacent to the trachea and those distant from the trachea before and after PSM (p > 0.05). The common complication observed after surgery was permanent recurrent laryngeal nerve injury, with prior studies reporting an incidence ranging from 2.3–3% (Ferrari et al. 2016; Hayward et al. 2013). In contrast, in this study, no patient experienced any permanent complications after ablation, and only one patient experienced hoarseness, which resolved within two months. For patients with tumors located adjacent to the “danger triangle”, ablation was performed with caution and close monitoring of the patient’s condition during. A case reported by Morvan demonstrated tracheal necrosis after RFA for a benign thyroid nodule under general anesthesia (Morvan et al. 2022). However, at our institution, local anesthesia was routinely performed for thyroid tumor ablation to enable real-time patient feedback and facilitate necessary adjustments. Although the retrospective nature of this study could lead to an underestimation of the complication incidence, we identified several critical factors for reducing complications. Firstly, a comprehensive pre-ablation evaluation was paramount, involving the use of US, CEUS, and CT scans to assess tumor characteristics and determine the most appropriate ablation route. In addition, the combined use of multiple techniques and methods, including hydrodissection and leverage pry-off methods, was essential, particularly when dealing with tumors located adjacent to the trachea. The hydrodissection technique was implemented to increase the distance between the tumor margin and critical neck structures. The distance was further increased by the application of leverage pry-off method. With the application of moving-shot technique and the trans-isthmic approach, thermal injury to surrounding structures could be minimized.
This study has several limitations. Firstly, it was a retrospective study conducted at a single center, which may have resulted in selection bias. Secondly, the incidence of complications may be underestimated due to the retrospective nature. Thirdly, the identification of aggressive pathologic subtypes of PTMC may not have been accurate as PTMCs were diagnosed by core-needle biopsy or fine needle aspiration. Furthermore, the study’s sample size and follow-up time were insufficient for such an indolent tumor. Finally, further large cohort prospective studies performed in multi-centers with longer follow-ups are needed.
In conclusion, our results demonstrate that there was no difference in clinical outcomes between PTMC located adjacent to the trachea and those located distantly. RFA is an effective and safe alternative approach for managing eligible low-risk PTMC adjacent to the trachea.