Single-center, Prospective, Non-Randomized Control Clinical Trial of Retro-Auricular Single-Site Endoscopic Versus Open Surgery in Patients With Early Stage Papillary Thyroid Carcinoma
Phase: NA
Conditions: Papillary Thyroid Carcinoma
Sponsor: Sun Yat-sen University

Single-center, Prospective, Non-Randomized 
Control Clinical Trial of Retro‐auricular Single‐site 
Endoscopic Versus Open Surgery in Patients with 
Early Stage Papillary Thyroid Carcinoma 
 
 
 
Study Protocol 
 
 
 
 
 
Version date: January, 19, 2022 
 
 
 
 
 
 
 
 

Official Title 
Single-center, Prospective, Non-Randomized Control Clinical Trial of 
Retro‐auricular Single‐site Endoscopic Versus Open Surgery in 
Patients with Early Stage Papillary Thyroid Carcinoma 
Brief 
Summary 
The goal of this non randomized control clinical research study is to 
compare the cosmetic outcomes and efficiacy of retro‐auricular single‐
site endoscopic thyroid lobectomy and central lymph node dissection 
against conventional resection. 
Conditions  
Age: 18～70 years.Patients with early stage papillary thyroid carcinoma.   
Outcome 
Measures 
 
Primary Outcome Measure: postoperative cosmetic satisfaction 
scores  
 
Secondary Outcome Measures: 
 Cosmetic outcome: postoperative Vancouver Scar Scale 
 Surgical outcomes: CRP level, SAA level, intraoperative blood 
loss, VAS pain score, Operative time. 
 Clinicopathologic characteristics: tumor size, number of lymph 
nodes, the positive rate of lymph nodes. 
 Complication: complication rates and types 
Study 
Process 
 
Sample 
Size  
80(40 VS 40) 
Inclusion 
Criteria 
 
 Age 18-70 years old, no gender restrictions. 
 Fine-needle aspiration cytology(FNA) confirmed papillary thyroid 
carcinoma(PTC). 
 Early stage PTC (stage T1N0M0). 
 Preoperative ultrasonography showed unilateral glandular lobe 
malignant tumor and the largest diameter was not more than 2cm,  
without cervical lymph node metastasis and extensive metastasis. 
 Patients undergoing thyroid lobectomy and central lymph node 
dissection. 
 Patients who have signed an approved Informed Consent. 
Exclusion 
Criteria 
 Patients who do not accept case data collection for various reasons. 
 The clinical data unfit this study （at the discretion of the investigator）. 
 Patients who have undergone neck surgery or radiotherapy before this 
trail. 
 Patients who have uncontrolled hyperthyroidism. 
Elimination 
Criteria 
 Patients who violated the requirements of the research protocol. 
 The quality of data records is incomplete and inaccurate. 
 Lost cases. 
Study 
Completion  2023-06-30 
Locations 
1 

Groups 
RASSET group VS traditional open thyroid lobectomy group 
Masking 
and 
Allocation 
None (Open Label). Non-Randomized(patient decided his surgery 
approach). 
Statistical 
Analysis 
Plan  
In this clinical study, the test level α was set to be 0.05 on both sides; the 
test efficiency Power (ie, 1-β) was selected as 0.8 (ie, type II error β=0.2); 
The sum standard deviation is 5.54±1.75, and the mean and standard 
deviation of the score of the cosmetic effect evaluation scale of the 
experimental group is expected to be 3.92±1.4 1. The 1:1 parallel control 
method is used, and the sample size calculation formula is based on the 
mean comparison of the two samples. According to the calculation of 
PASS software, this study requires a sample size of about 72 people (36 
cases in each group). Considering the 10% dropout rate, the required 
sample size for each group is 40 cases, and a total of 80 cases in the two 
groups are required. 
All analyses were performed using SPSS 26.0, and a P value less than 
0.05 was considered significant. Normally distributed quantitative data are 
represented by mean (SD) [range]. Non-normally distributed quantitative 
data are represented by M（QR）. Comparison between groups was 
performed using the Mann-Whitney U test. 
Categorical data are expressed as frequencies and percentages. 
Comparisons between groups were performed using theχ2 test or Fisher's 
exact test. 
 
Study Protocol 
1.Background 
Thyroid cancer is one of the most common malignant tumors in the head and neck. 
Among it, papillary thyroid carcinoma accounts for about 70% of thyroid cancer. The 
degree of malignancy is low, but there is a tendency for multicentricity, and cervical lymph 
node metastasis occurs early. Due to the development of diagnosis technology, the 
amount of papillary microcarcinoma is getting higher and higher. At the same time, the 
change of aesthetic makes young women pursue a scarless neck1, 2. 
Surgery is the first choice of treatments for early-stage thyroid cancer.3, 4 Traditional open 
surgery tended to leave a long scar on the neck, which affects the cosmetic outcome. At 
present, many reported approaches, such as trans-areola approach5, trans-axillary 
approach6, trans-oral approach 7, 8or some combined approaches9, all have wider flap 
dissection or greater body trauma, and at the same time, these above approaches are 
difficult to achieve complete dissection of central lymph nodes10.  
Therefore, based on the experience of transauricular hairline endoscopic 
thyroidectomy11-13, we established a new operative method-the Retro-auricular single-site 
endoscopic thyroidectomy (RASSET). The incision is only 3cm and located at the 

posterior sulcus of the auricle, which can meet the cosmetic needs. Compared with other 
endoscopic approaches, the dissection area is small and the flap dissection is small, 
which may reduce the surgical trauma. The RASSET is easy to resect the upper pole of 
the thyroid gland, and can achieve complete dissection of the central lymph nodes.  
The article titled " A comparative study between retro‐auricular single‐site endoscopic 
thyroidectomy and transoral endoscopic thyroidectomy vestibular approach: a single‐
center retrospective analysis " has been published in " Chin J Surg "14. Guangdong 
Medical Information Research Institute recognized that there was no report of endoscopic 
thyroid surgery for this approach at home and abroad, and it also passed the new 
technology evaluation in the Sun Yat-sen University Cancer Center, and was recognized 
as an international leader. 
 
2. Study purpose 
 
Primary purpose: 
Comparing the cosmetic outcomes of the retroauricular approach and the open group by 
comparing postoperative cosmetic satisfaction scores. (Appendix 1) 
 
Secondary purpose: 
 
Comparing the degree of surgical trauma between the retroauricular group and 
the open group by comparing the level of CRP and SAA, blood loss, VAS pain 
score, and postoperative drainage. 
 
Comparing the clinicopathologic characteristics between the retroauricular group 
and the open group by comparing the number of resected lymph nodes, and the 
positive rate of lymph nodes. 
 
Comparing the safety between the retroauricular group and the open group by 
comparing the types and rate of complications between the two groups. 
 
Primary Outcome Measure: postoperative cosmetic satisfaction scores  
 
Secondary Outcome Measures: 
 
Cosmetic outcome：postoperative Vancouver Scar Scale 

 
Surgical outcomes: CRP level, SAA level, blood loss, VAS pain score, 
postoperative drainage volume, Operative time. 
 
Clinicopathologic characteristics: tumor size, number of lymph nodes, the 
positive rate of lymph nodes. 
 
Complication: complication rates and types.
 
3. Study Eligibility 
 
Inclusion Criteria: 
 
Age 18-70 years old, no gender restrictions. 
 
Fine-needle aspiration cytology(FNA) confirmed papillary thyroid 
carcinoma(PTC). 
 
Early stage PTC (stage T1N0M0). 
 
Preoperative ultrasonography showed unilateral glandular lobe malignant tumor 
and the largest diameter was not more than 2cm,  without cervical lymph node 
metastasis and extensive metastasis. 
 
Patients undergoing thyroid lobectomy and central lymph node dissection. 
 
Patients who have signed an approved Informed Consent. 
 
Exclusion Criteria: 

 
Patients who do not accept case data collection for various reasons. 
 
The clinical data unfit this study （at the discretion of the investigator）. 
 
Patients who have undergone neck surgery or radiotherapy before this trail. 
 
Patients who have uncontrolled hyperthyroidism. 
 
Withdrawal criteria: 
(A withdrawal case refers to a patient who withdraws from treatment for various reasons in 
study. Patients with the following conditions will be withdrawn from investigational 
treatment.) 
 
The patient himself or his legal representative requests to withdraw. 
 
In the opinion of the investigator, the patient's continued participation in the study 
will be detrimental to his health. 
 
Elimination Criteria: 
 
Patients who violated the requirements of the research protocol. 
 
The quality of data records is incomplete and inaccurate. 
 
Lost cases. 
4. Case Screening 
 
examination items 
All cases must complete the following examination items before being considered for 
entry into this study. It is generally required to be completed within 7 days before 
treatment. 
 
Complete medical history and comprehensive physical examination, including 
symptoms, signs and specialist examination. 
 
Check items that must be done before routine treatment, including:Blood routine: 
neutrophil/lymphocyte ratio,Coagulation function: d-dimer,Serological tests: CRP, SAA, 
procalcitonin, calcium level,Thyroid function: TSH level, parathyroid hormone 
level,Thyroid ultrasonography, thyroid Computed tomography scan if necessary,Chest 
X-ray, abdominal ultrasonography, electrocardiogram. 
The above examinations are all routine preoperative examinations, which do not 
cause additional financial burden on patients. 
 
Case screening 
According to various examinations, those who meet the inclusion criterias are screened 
out.The patients entered the study after completing the required examinations and being 
evaluated according to the inclusion criterias. Then sign the informed consent form and 
get treatment. 
5. Study Process 

 
6. Surgical Technique 
 
Retro-auricular single-site endoscopic thyroidectomy (RASSET ) 
For the RASSET technique, in the beginnig, patient was placed in a supine position with 
slight neck bending. When the lower pole of the thyroid gland was going to be dissected, 
the patient was placed in a supine position with slight neck extension. Mark the operation 
path on the surface. Slit the skin, subcutaneous tissue and superficial cervical fascia in 
turn. Expose the middle branch of the great auricular nerve and the sternocleidomastoid 
muscle under direct vision. The working space was created in the superficial layer of deep 
cervical fascia between the sternocleidomastoid muscle and the platysma muscle, which 
meets the principle of membrane anatomy. The area of flap dissection just includes the 
anterior cervical muscle and the anterior edge of the sternocleidomastoid muscle, which is 
so narrow to minimize the traumatic dissection. Pulling apart the anterior cervical muscle 
and the sternocleidomastoid muscle along the deep cervical fascia can fully expose the 
thyroid gland, the recurrent laryngeal nerve (RLN) and common carotid artery that are 
surrounded by the middle layer of deep cervical fascia and ensure that tumor and central 
lymph nodes en‐bloc resection can be operated in the middle layer of deep cervical 
fascia to conform the natural anatomical region. For details, please refer to "A 
comparative study between retro‐auricular single‐site endoscopic thyroidectomy and 
transoral endoscopic thyroidectomy vestibular approach: a single‐center retrospective 
analysis". 

 
 
traditional open surgery 
For traditional open surgery, the patient was placed in a supine position. A 4-6cm 
transverse incision was made. Subplatysmal flaps were dissected up to the thyroid 
cartilage and down to the sternal notch.The strap muscles were separated in the midline 
to expose the thyroid gland. Lateral dissection of the thyroid gland was performed. The 
middle thyroid vein was ligated. Superior thyroid vessels were individually ligated close to 
the thyroid gland. The RLN was identified and dissected near the inferior thyroid artery. 
Branches of the inferior thyroid vessels were ligated, preserving the lower parathyroid 
gland. Berry ligament was then dissected, and finally the isthmus was transected. The 
thyroid and central lymph nodes were resected. For details, please see "Clinical Practice 
and Skills in Head and Neck Oncology Surgery". 
7. Outcome Measures   
 
Baseline Characteristics of Patients 
Gender, Age, BMI, Tumor size, Pathological type, Tumor location, ASA grade. 
 
Postoperative Outcomes 
 
Cosmetic outcome: postoperative Vancouver Scar Scale 1 and 3 months from 
surgery, postoperative cosmetic satisfaction scores 1 month from surgery. 
 
Surgical outcomes: CRP level, SAA level, Drainage volume (ml), intraoperative 
blood loss, VAS pain score, Operative time. 
 
Clinicopathologic characteristics: tumor size, number of lymph nodes, the 
positive rate of lymph nodes. 
 
Complications: complication rates and types. 
 
Primary Outcome Measure: postoperative cosmetic satisfaction scores 3months from 
surgery. 
8. Code of Ethics 

 
Informed consent 
Before each patient was enrolled in this study, the research investigators are responsible 
for a complete and comprehensive introduction to the surgical method of this study, its 
possible side effects and possible risks, and let patients know their rights, risks and 
benefits to be assumed. Patients should have signed informed consent before enrollment. 
 
Ethical norms and policies and regulations 
This clinical trial must comply with the Declaration of Helsinki (2000 Edition), the Good 
Clinical Practice (GCP) promulgated by the SFDA, and related regulations. Before the 
start of the trial, the study could be started only after the protocol was approved by the 
ethics committee of the lead unit. Any modification of the trial protocol during clinical 
research should be reported to the ethics committee and filed. 
 
Obtaining ethics approval 
Ethical approval has been obtained. 
9. Quality Assurance 
In order to ensure that this trial can be carried out in strict accordance with the clinical 
research protocol, during the entire process of the clinical trial, clinical investigators and 
clinical sponsors should behave in strict accordance with the requirements of the Good 
Clinical Practice for Drugs (GCP), and be sure to follow the trial procedures. Standardized, 
accurate test data, and reliable research conclusions. Specific requirements are as 
follows: 
 
Requirements for collaborators: 
 
Lectures on clinical programs, CRF filling, etc. are given to the researchers 
before the clinical start. 
 
Send clinical monitors to conduct on-site inspections. 
 
Ensure that the researchers can keep in touch with the researchers at any time 
by telephone or email. 
 
Requirements for researchers: 
 
Responsible for obtaining the "Informed Consent" signed by each subject or his 
agent. 
 
Complete the case report form (CRF) carefully as required. 
 
Regular visits. 
 
Completely maintain records of clinical records, and original medical records of 
subjects. 
10. Data Processing and Preservation 
 
Case report form (CRF) 
The case report form should be filled out by investigators, and the CRF form should be 
filled out in time to ensure accurate content and timely summary. Generally, the CRF form 
should not be altered. If there is an error that needs to be revised, it should be signed at 
the revised place. The CRF form is in triplicate, and after the trial is over, it will be handed 
over to the clinical team leader hospital, the sponsor and the trial hospital for preservation. 
Data entry was performed after the completed case report was reviewed by the clinical 
monitor. The contents of the case report form are no longer modified. 

 
Create a database 
After receiving the CRF form, the statistician will verify the question by the researcher, and 
the researcher should answer and return as soon as possible. Statisticians will establish a 
database at the same time. After the database is reviewed, the data will be locked by the 
principal investigators, sponsors, statistician and clinical monitors. To ensure data security, 
irrelevant personnel cannot access and modify the data, and the data must be backed up. 
 
Storage of data 
The researcher should keep the data intact. According to the principle of GCP in China, 
for the investigators or hostipals, the data storage should be more than 5 years. 
11. Statistical analysis 
Professional statisticians undertake statistical analysis tasks and participate in the whole 
process from experimental design, implementation to analysis and summary. After the 
study protocol and case report form are completed, a statistical analysis plan shall be 
formulated. After some necessary modifications shall be made during the study process 
as required, and a statistical analysis report shall be provided after the data analysis is 
completed.  
 
Sample size 
In this clinical study, the test level α was set to be 0.05 on both sides. the test efficiency 
Power (ie, 1-β) was selected as 0.8 (ie, type II error β=0.2). The sum standard deviation is 
5.54±1.75, and the mean and  standard deviation of the score of the cosmetic effect 
evaluation scale of the experimental group is expected to be 3.92±1.41. The 1:1 parallel 
control method is used, and the sample size calculation formula is based on the mean 
comparison of the two samples. According to the calculation of PASS software, this study 
requires a sample size of about 72 people (36 cases in each group). Considering the 10% 
dropout rate, the required sample size for each group is 40 cases, and a total of 80 cases 
in the two groups are required. 
 
Statistical Analysis 
All analyses were performed using SPSS 26.0, and a P value less than 0.05 was 
considered significant. Normally distributed quantitative data are represented by mean 
(SD) [range]. Non-normally distributed quantitative data are represented by M（QR）. 
Comparison between groups was performed using the Mann-Whitney U test. Categorical 
data are expressed as frequencies and percentages. Comparisons between groups were 
performed using theχ2 test or Fisher's exact test. 
12. Follow-up 
During the study period, each enrolled case was independently archived and registered 
for evaluation (CRF), and a resident physician was to be hired to be responsible for 
follow-up, registration, filling, and storage. After the end of treatment, the enrolled patients 
will be reviewed in the outpatient clinic in the first month after surgery, and then will be 
followed up regularly for 3-6 months until the death of the patient or the end of the study. 
The content of each review must include: thyroid function, parathyroid hormone level, 
thyroid ultrasonography. Questionnaires were conducted in the first and third months after 
surgery, and the scores of the Beauty Evaluation Scale and the Postoperative Scar Scale 

were recorded and counted. 
13. Study Start and Completion 
Study Start: March 1, 2022    
Anticipated Study Completion: June 30, 2023   
A total of 40 patients in the RASSET group and 40 patients in the open group will be 
Enrolled, follow up 1 and 3 months after the operation, and the clinical data will be 
collected and analyzed statistically. 
 
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Transoral Endoscopic Thyroidectomy Vestibular Approach. Jama Surg. 2018;153(1):21. 
 2. Lee DW, Ko SH, Song CM, Ji YB, Kim JK, Tae K. Comparison of postoperative cosmesis in 
transaxillary, postauricular facelift, and conventional transcervical thyroidectomy. Surgical Endoscopy. 
2020;34(8):3388-3397. 
 3. Filetti S, Durante C, Hartl D, et al. Thyroid cancer: ESMO Clinical Practice Guidelines for 
diagnosis, treatment and follow-up. Ann Oncol. 2019;30(12):1856-1883. 
 4. Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association Management 
Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American 
Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. 
Thyroid. 2016;26(1):1-133. 
 5. Liang J, Zhan L, Xuan M, et al. Thyroidectomy for thyroid cancer via transareola single-site 
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Surg. 2017;48:9-15. 
 7. Nguyen HX, Nguyen HX, Nguyen HV, Nguyen LT, Nguyen TTP, Le QV. Transoral Endoscopic 
Thyroidectomy by Vestibular Approach with Central Lymph Node Dissection for Thyroid 
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 8. Nakajo A, Arima H, Hirata M, et al. Trans-Oral Video-Assisted Neck Surgery (TOVANS). A new 
transoral technique of endoscopic thyroidectomy with gasless premandible approach. Surgical 
Endoscopy. 2013;27(4):1105-1110. 
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Thyroid Surgery. Thyroid. 2016;26(3):331-337. 
10. Duek I, Duek OS, Fliss DM. Minimally Invasive Approaches for Thyroid Surgery—Pitfalls and 
Promises. Curr Oncol Rep. 2020;22(8). 
11. Schardey HM, Barone M, Portl S, von Ahnen M, von Ahnen T, Schopf S. Invisible scar 
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results. Surg Endosc. 2008;22(4):813-820. 
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Appendix 
Appendix 1 Cosmetic satisfaction questionnaire 
Q1. How satisfied are you with your neck scar or a scarless neck? 
Very satisfied(1) Satisfied(2) Average(3) Dissatisfied(4) Verydissatisfied(5) 
Q2. How satisfied are you with the contour of your neck? 
Very satisfied(1) Satisfied(2) Average(3) Dissatisfied(4) Verydissatisfied(5) 
Q3. Do you think others look at your neck scar? 
Absent (0) Sometimes (1) Frequent (2) Always (3) 
Q4. Do you try to conceal your scar? 
Absent (0) Sometimes (1) Frequent (2) Always (3) 
Q5. Does your neck scar influence your choice of clothes? 
Absent (0) Sometimes (1) Frequent (2) Always (3) 
Q6. How often do you think about your scar? 
Absent (0) Sometimes (1) Frequent (2) Always (3) 
Appendix 2 Vancouver scar scale score 
 
Appendix 3 AJCC 8th Edition/TNM Classification System for 
Differentiated Thyroid Carcinoma