Dutch De-escalation pilot Study

The worldwide incidence of papillary thyroid cancer (PTC) is increasing and thyroid cancer is the most common endocrine malignancy worldwide. The incidence rises due to increased use of imaging modalities such as ultrasonography, MRI and PET/CT scan, which mainly leads to the identification of thyroid incidentalomas, small well-differentiated papillary thyroid carcinomas. Despite a shift towards a less aggressive treatment in the USA, described in the latest American Thyroid Association guideline, the Dutch guidelines are more aggressive in treating PTC. They recommend a total thyroidectomy (TTx) followed by radioactive iodine (RAI) in all patients with a PTC >1 cm. This treatment strategy comes with significant costs and morbidity rates caused by hypothyroidism, iatrogenic hypo-parathyroidism, recurrent laryngeal nerve damage, dysgeusia and xerostomia, resulting in a poor quality of life. The stable overall survival rate suggests widespread overtreatment following current treatment strategy. Therefore, changing treatment strategies for low-risk PTC patients is of great importance. This is reflected by the 2015 ATA guidelines stating that hemi thyroidectomy is sufficient for patients with low-risk PTC based on large national USA registration database studies. These studies show neither survival benefit nor difference in recurrence rate between TTx versus hemi thyroidectomy (HTx) in this group of patients. Unfortunately, the lack of strong evidence, such as randomized trials demonstrating equivalent oncological outcomes is currently withholding widespread worldwide de-escalation and is urgently required to update guidelines in non-American countries. Prior to performing such a large-scale randomized controlled trial, a pilot study is necessary to assess willingness to participate and adherence to the active surveillance strategy. This pilot study will function as a stepping stone to the aforementioned national RCT.

A hemithyroidectomy followed by active surveillance with ultrasonography results in the same oncological outcomes and survival as a total thyroidectomy and post-operative radioactive iodine (RAI) in patients with unifocal PTC 1-4 cm

The primary endpoint consists of the participation of patients eligible for the study, which will be calculated in percentages (%). This will be calculated when all the patients are included.

Secondary outcomes
1. Time needed to include 12 patients, which will be calculated in months after inclusion of the patients.
2. Reasons for patients to deny participation. Patients can describe the reason(s) for denial in free text. The treating physician asks an open-ended question and notes the reason for refusing participation. This will be sent to the study coordinator. This will be registered during inclusion and duration of the study.
3. Total number of patients and percentage of patients in the active surveillance group who wish to be treated according to the current guidelines which is calculated in a categorical number (n) and a percentage (%) after inclusion of the 12 patients.
4. QOL questionnaires will be sent to the study participants before surgery, after 6 months and 12 months. These questionnaires will be saved in Castor EDC and will be evaluated after the end of the study.
5. Logistical hurdles which are described in free text, during the duration of the study. These will be evaluated after the end of the study.

Study treatment; hemithyroidectomy and active surveillance. Standard treatment; total thyroidectomy with RAI.