Recurrence and postoperative quality of life after surgical resection of unilateral cT1–T3N1bM0 papillary thyroid carcinoma

Introduction

Thyroid carcinoma is a prevalent form of endocrine malignant tumor worldwide, representing 3.8% of newly diagnosed malignant tumors. In comparison to other cancers, thyroid carcinoma incidence has rapidly increased over the past two decades, with a male to female ratio of approximately 1:3 (1). The disease can be categorized into four main types based on pathological findings, including papillary thyroid carcinoma (PTC), medullary thyroid carcinoma, follicular thyroid carcinoma, and undifferentiated thyroid carcinoma, with PTC accounting for over 90% of all cases. Thanks to advancements in medical care, the 5-year relative survival rate of thyroid carcinoma patients in China has increased to 84.3% (2). Given PTC’s low mortality risk, it is crucial to focus on improving postoperative quality of life for affected patients (3).

Total thyroidectomy or non-total thyroidectomy, which means unilateral thyroidectomy and isthmus resection with or without partial resection of the contralateral thyroid lobe, coupled with central regional lymph node dissection and unilateral neck lymph node dissection (UNLND), remains the primary surgical method for treating unilateral PTC with unilateral cervical lymph node metastasis (4). The scope of the initial surgical resection of thyroid carcinoma has been found to be closely linked with its postoperative recurrence rate. In cases where PTC exhibits lateral neck lymph node metastasis, it is advisable to perform a simultaneous resection of the contralateral lobe alongside conventional regional lymph node dissection to minimize the probability of recurrence (5). PTC without a malignant tumor on the contralateral gland lobe can be preserved to restore thyroid function and mitigate postoperative complications (6-8). Notably, the likelihood of complications following total thyroidectomy is significantly greater than that following non-total thyroidectomy (9).

As highlighted in the preceding research background, there is a paucity of studies investigating the relationship between surgical approaches and postoperative survival benefits in patients with unilateral cT1–T3N1bM0 PTC. Traditionally, total thyroidectomy has been the primary surgical method. However, updated research views on thyroid carcinoma treatment have emerged, aimed at reducing the possibility of excessive medical intervention and enhancing postoperative quality of life without increasing the risk of postoperative recurrence. Standardized surgical interventions and postoperative management strategies can help to evaluate the likelihood of tumor recurrence, promote patient survival rates, and improve their quality of life. Therefore, this retrospective study was conducted to compare the survival benefit of total/non-total thyroidectomy + central region lymph node dissection + UNLND in patients with unilateral cT1–T3N1bM0 PTC, providing a further basis for selecting surgical methods for these patients. We present this article in accordance with the STROBE reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-24-178/rc).

Methods

Research object

In this retrospective study, we aimed to examine the surgical outcomes of patients with unilateral cT1–T3N1bM0 PTC who received treatment for UNLND at Harbin Medical University Cancer Hospital between January 2008 and December 2018. The inclusion criteria were meticulously selected based on preoperative imaging examination, preoperative or postoperative pathology confirmation.

Specifically, the inclusion criteria were: (I) unilateral thyroid malignant tumor observed via preoperative imaging, with no nodules in the opposite gland lobe or benign nodule measuring ≤2 cm; (II) confirmation of unilateral PTC via preoperative or postoperative pathology with complete relevant information; (III) treatment for clinically or pathologically confirmed unilateral lateral cervical lymph node metastasis using UNLND; (IV) no previous surgery or planned iodine-131 treatment. The exclusion criteria comprised of (I) preoperative evidence of distant metastasis; (II) postoperative pathology indicating thyroid isthmus or bilateral carcinoma; (III) administration of iodine-131 treatment postoperatively; (IV) postoperative pathology indicating non-PTC.

Consequently, a total of 362 patients with unilateral cT1–T3N1bM0 PTC and fulfilling multiple requirements were enrolled in this study, with 88 patients who underwent non-total thyroidectomy classified as group A and 274 patients who underwent total thyroidectomy classified as group B. All included patients were followed up for their postoperative quality of life, with any patients who declined to participate or were lost to follow-up being excluded from the study. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Ethics Committee of the Cancer Hospital Affiliated with Harbin Medical University (No. XJS2022-39), and informed consent was obtained from the patients.

Research methods

Data collection

The preoperative evaluation in this study involved the use of seven serological tests to assess thyroid function and thyroid neck ultrasound to determine the location, number, shape, and size of the primary tumor and suspected cervical lymph node involvement. Only patients with cervical lymph node enlargement were included in the study. The serological tests were also used to detect the presence of Hashimoto’s thyroiditis. Basic patient information, such as age, sex, and presence of Hashimoto’s thyroiditis, as well as pathological data including postoperative pathological type, number and size of cancer foci, invasion of surrounding tissues by cancer foci, and contralateral gland status, were collected.

All patients underwent total thyroidectomy or non-total thyroidectomy + UNLND with at least ipsilateral central regional lymph node dissection. The surgeon collaboratively determined the extent of the surgical procedure by considering the established criteria and patient preferences. Lymph node dissection was performed in strict accordance with the Chinese Society of Clinical Oncology (CSCO) guidelines for differentiated thyroid management. All parathyroid glands were preserved in situ during surgery, but when preservation in situ was unsatisfactory, parathyroid autotransplantation was performed. According to American Thyroid Association (ATA) 2015, we recommend patients to be treated with iodine-131 when their risk of postoperative recurrence is rated as medium-risk or higher and exclude such patients from the study. However, a proportion of patients forgo iodine-131 treatment for financial or other non-medical reasons and we included these patients in the study.

Evaluation and follow-up of postoperative complications

The postoperative evaluation and follow-up of patients were conducted through various assessments, including temporary and permanent recurrent laryngeal nerve palsy, temporary and permanent hypocalcemia, postoperative dosage, Hospital Anxiety and Depression Scale (HADS) scores (10), postoperative quality of life analysis (11), postoperative recurrence, recurrence time, and further treatment after recurrence. Patients were monitored at least once a year postoperatively through seven serological tests of thyroid function and thyroid neck ultrasound.

Temporary recurrent laryngeal nerve injury was defined as a decrease or disappearance of vocal cord activity within 6 months postoperatively, whereas permanent recurrent laryngeal nerve injury was defined as the decrease or disappearance of vocal cord activity persisting for more than 6 months postoperatively. Temporary hypocalcemia was defined as having a blood calcium level of less than 2.1 mmol/L measured within 6 months postoperatively or requiring a calcium supplement. Permanent hypocalcemia was defined as having a blood calcium level of less than 2.1 mmol/L measured over 6 months postoperatively or requiring a calcium supplement (12).

Postoperative recurrence was confirmed through imaging, cytology, and histopathology. Subsequently, the postoperative recurrence rates were compared between the two groups after baseline data had been adjusted by propensity score matching (PSM). The final follow-up deadline for this study was January 2022.

Investigation of the postoperative quality of life of patients

During the follow-up period, patients were assessed using a questionnaire to understand the impact of the scope of surgery on their postoperative quality of life. The questionnaire included the HADS and a postoperative quality of life analysis table, which evaluated the quality of life of patients with malignant tumors. The postoperative quality of life analysis table contained eight symptoms, including review frequency, hoarseness, abnormal cold and hot sensation, rapid heartbeat, dysphagia, constipation or diarrhea, calcium deficiency symptoms, and reduced willingness to take medicine. Each symptom was scored from 0 to 10, with “0” indicating no symptoms and “10” indicating extreme symptoms. Scores of 1–3, 4–6, and 7–10 represented mild, moderate, and severe symptoms, respectively. The questionnaire was administered by professionals through outpatient, network, and telephone follow-up.

Statistical analysis

Statistical analysis was performed using SPSS 26.0 software. For normally distributed quantitative data, mean ± standard deviation was used for descriptive statistics, and the two independent samples t-test (represented by t-value) was employed for between-group comparisons. For skewed quantitative data, descriptive statistics were presented as median and interquartile range [M (P25, P75)], and the Wilcoxon rank-sum test (represented by Z value) was used for between-group comparisons. Qualitative data were described using frequencies and percentages, and the χ² test or Fisher’s exact test was used to compare the composition (between the two groups (represented by χ² values). The significance level for hypothesis testing was set at α=0.05, with P<0.05 considered statistically significant.

Results

Baseline data

A total of 362 patients with cT1–T3N1bM0 PTC were included in the study, with a median age of 43 [14–76] years and a male-to-female ratio of 1:2.93. Of these, 88 patients in group A underwent non-total thyroidectomy + ipsilateral central zone lymph node dissection + UNLND; 35.4% (97/274) of patients in group B underwent total thyroidectomy + bilateral central zone lymph node dissection + UNLND and 64.6% (177/274) underwent total thyroidectomy + ipsilateral central zone lymph node dissection + UNLND. Postoperative pathology revealed that 74 cases were multifocal, 175 cases had invasion of the capsule and 37 cases had extrathyroid invasion. Table 1 shows the comparison results of the baseline data of the two groups of patients.

The comparison of baseline data between the two groups showed significant differences in age (χ²=10.962, P=0.001), sex (χ²=5.906, P=0.02), multifocal (χ²=5.515, P=0.02), contralateral glandular nodule (χ²=34.616, P<0.001), clinical Tumor, Node, Metastasis (TNM) stage (χ²=11.340, P=0.001), and complication rate (χ²=4.265, P=0.04). Specifically, patients in group A were significantly younger and had a lower incidence of contralateral glandular nodules with a lower clinical TNM stage, whereas those in group B had a lower incidence of multiple cancer foci. In particular, the complication rate was significantly higher in group B than in group A. The differences in age, clinical TNM stage, sex, contralateral glandular nodule, multifocal and complication between the two groups were statistically significant.

Complications

Table 2 presents the comparison of postoperative complications between the two groups. Notably, there were statistically significant differences in the incidence rates of temporary recurrent laryngeal nerve injury, and temporary hypocalcemia between group A and group B. Specifically, the incidence rate of temporary recurrent laryngeal nerve injury in group A was significantly lower than that in group B (χ²=4.630, P=0.03). Moreover, the incidence rates of temporary hypocalcemia in group B were higher than those in group A (χ²=3.954, P=0.047). In contrast, although the incidence rate of postoperative hemorrhage rate was higher in group B compared to group A, the difference was not statistically significant (P>0.99). Therefore, the results suggest that the incidence of temporary recurrent laryngeal nerve injury, temporary hypocalcemia were significantly different between the two groups, with higher incidence rates observed in group B.

Comparison of postoperative recurrence

Among the 362 patients, 3.4% (3/88) patients in group A and 5.1% (14/274) in group B experienced tumor recurrence. In group A, recurrence was observed in three patients: one patient had imaging showing possible malignancy in the contralateral thyroid gland, one patient had imaging suggesting possible malignancy in the ipsilateral cervical lymph node, and one patient was confirmed to have ipsilateral cervical lymph node metastasis after the second operation. In group B, imaging showed that 12 patients had possible malignant ipsilateral cervical lymph nodes, one patient had possible malignant contralateral cervical lymph nodes, and one patient had possible malignant bilateral cervical lymph nodes.

Following the application of PSM analysis, a sample of 76 pairs was obtained for the PSM group A and PSM group B (Table 3). No statistically significant differences were observed between the two groups with regard to age, gender, tumour size, multifocality, contralateral glandular nodule, extrathyroidal invasion, thyroiditis, the presence of contralateral glandular nodules, clinical TNM stage, pathological T stage and postoperative follow-up time. And there was no statistically significant difference in postoperative recurrence rates when comparing the two groups of patients (χ²=0.150, P=0.70). Moreover, the patients were categorized into recurrence and non-recurrence groups based on whether they experienced recurrence (Table 4). Comparison of the two groups of patients revealed a correlation between postoperative recurrence and tumour size (χ²=4.497, P=0.03), extrathyroidal invasion (χ²=5.133, P=0.02), and pathological T stage (χ²=7.663, P=0.02).

Comparison of patients’ psychological conditions postoperatively

The HADS scores (Table 5) collected through follow-up showed that the majority of patients in both group A and group B had moderate to severe anxiety and depression, with 67.0% and 71.9% of patients, respectively, scoring 11–20 on the HADS questionnaire. However, there was no significant difference in HADS scores between the two groups (χ²=1.266, P=0.53) (Table 5). In group A, 8.0% of patients scored 0–7 without anxiety and depression tendency, while in group B, 5.1% of patients scored 0–7 without anxiety and depression tendency. Additionally, 22 (25.0%) patients in group A and 63 (23.0%) patients in group B scored 8–10, indicating a mild state of anxiety and depression.

Comparison of postoperative quality of life of patients

Table 6 shows the comparison of the postoperative quality of life of patients in the two groups. The results indicate that patients in group A had lower scores on hoarseness, calcium deficiency symptoms, and willingness to reduce medication than those in group B. Specifically, the comparison results are as follows—(I) hoarseness: the score in group A was significantly lower than that in group B (P<0.001); (II) calcium deficiency symptoms: the score in group A was significantly lower than that in group B (P<0.001); (III) willingness to reduce medication: the score in group A was significantly lower than that in group B (P<0.001). There was a significant difference in the postoperative quality of life between the two groups, indicating that patients in group A had better postoperative quality of life than those in group B.

Discussion

The preoperative assessment of patients with PTC is critical in determining the surgical approach. While the long-term survival rate for PTC is favorable, the goal of surgery is to maximize postoperative quality of life. The balance between minimizing postoperative complications and sufficiently resecting the tumor has led to ongoing debate regarding the optimal surgical approach for PTC. Recent clinical guidelines have been adjusted to reflect this debate (13). Our study supports the use of non-total thyroidectomy with central lymph node dissection and UNLND in patients with unilateral cT1–T3N1bM0 PTC with full consideration of indications. This approach reduces the risk of postoperative complications and improves postoperative quality of life.

The literature suggests that total thyroidectomy carries a significantly higher risk of postoperative complications compared to non-total thyroidectomy (14), while without clear evidence of a reduction in recurrence or added benefit survival. Probably the non-total thyroidectomy based on risk stratification, in patients with differentiated thyroid cancer (DTC) with diameter <2 cm without other specific risk factors could be safe (15). Our study also found that total thyroidectomy was associated with a significantly higher incidence of temporary recurrent laryngeal nerve injury, temporary and permanent hypocalcemia compared to non-total thyroidectomy. Notably, patients with permanent hypoparathyroidism or recurrent laryngeal nerve injury are at increased risk for depression and anxiety postoperatively (16). Our study showed that anxiety and depression were common in both groups, although scores were lower in the non-total thyroidectomy group, which suggests that the extent of thyroid surgery impacts postoperative quality of life and psychological well-being. Thus, surgeons should carefully consider multiple factors when selecting the optimal surgical approach, weighing the pros and cons of prognosis and complications to develop a personalized treatment.

The choice of surgical approach for patients with intermediate to low-risk papillary carcinoma has been controversial due to conflicting data on its impact on prognosis. Liu et al. conducted a retrospective study on 1,087 such patients and found no statistical difference in the 10-year disease-free survival rate and disease-specific survival rate between total resection and non-total resection groups (17). Su and Li investigated risk factors for recurrence in PTC patients who underwent total thyroidectomy and therapeutic UNLND over an 18-year period (18), identifying multifocal tumors measuring ≥1 cm and extrathyroid and lymphatic vascular invasions as risk factors. Similarly, our study also revealed that tumour size (≥1 cm), the presence of extrathyroidal invasion and higher pathological T stage were associated with an increased risk of recurrence. It is noteworthy that in both group A and group B, there was recurrence in the contralateral glandular lobe or contralateral cervical lymph node, which may be related to inadequate clearance of the contralateral central regional lymph node (19). Contrary to James et al. (5), our findings suggest that the presence of a contralateral nodule and total thyroidectomy do not significantly affect recurrence. In conclusion, non-total thyroidectomy may be considered for patients with intermediate to low-risk unilateral cT1–T3N1bM0 PTC, such as tumour size (<1 cm), without extrathyroidal invasion and pathological T stage (< T3).

Our study revealed that there were differences in the selection of surgical method based on patient demographics and clinical characteristics. Specifically, the proportion of male choosing non-total thyroidectomy was higher than those choosing total thyroidectomy. However, we do not know the exact reason at present, perhaps because surgeons think that men have a greater demand for physiological thyroid hormones than women, which needs to be further explored. Additionally, patients under 55 years of age were more likely to choose non-total thyroidectomy compared to those over 55 years of age. This may be due to the lower clinical stage and longer survival of younger patients, and the benefits of preserving gland outweigh the risks to the patient. Our study also confirmed this. There is no significant difference in the long-term recurrence rate of unilateral cT1–T3N1bM0 PTC between total thyroidectomy and non-total thyroidectomy. On the contrary, patients who underwent non-total thyroidectomy had better postoperative quality of life because the gland was preserved. Notably, when the nodule was bilateral at initial diagnosis, despite they are benign according to the pathology exam, patients were more likely to choose total thyroidectomy rather than non-total thyroidectomy. This may be due to the anxiety caused by the initial diagnosis of bilateral nodules, which leads patients to make a relatively excessive medical decision such as total thyroidectomy (20). And due to the lack of early clinical evidence support, doctors are unable to give more reasonable suggestions.

This retrospective study has several limitations that need to be acknowledged. The potential for information bias exists due to the prolonged follow-up period and the reliance on patients’ memories for postoperative recovery information. Additionally, the lack of uniformity in surgical techniques among different surgeons could have affected the research findings. The sample size from a single center was also inadequate, and there was no information available on thyroid-related gene detection for the patients, which could have led to uncontrolled data analysis deviations. Future research should focus on prospective randomized controlled multicenter studies to obtain more extensive data. Nonetheless, the low recurrence rate of postoperative diseases and the absence of patient deaths during the follow-up period in this study support the notion that early standardized surgical treatment can significantly improve patients’ overall survival rate.

Conclusions

In conclusion, for patients with a nodule of contralateral gland measuring ≤2 cm who have an intermediate to low-risk unilateral cT1–T3N1bM0 PTC, such as tumour size (<1 cm), without extrathyroidal invasion and pathological T stage (< T3), preservation of the contralateral gland does not affect tumour recurrence. Gland preservation may improve the patient’s prognosis and quality of life while reducing the incidence of complications. Non-total thyroidectomy with SNLND can be considered as a viable option for the above-mentioned intermediate to low-risk patients who do not have a strong desire for total thyroidectomy. It can significantly improve the patient’s postoperative quality of life.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-24-178/rc

Data Sharing Statement: Available at https://gs.amegroups.com/article/view/10.21037/gs-24-178/dss

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-24-178/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-24-178/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Ethics Committee of the Cancer Hospital Affiliated with Harbin Medical University (No. XJS2022-39), and informed consent was obtained from the patients.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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