Deciding on Active Surveillance or Surgery for Primary Management of Low Risk Papillary Thyroid Cancer

Study Overview
=================
Brief Summary
-----------------
This is a prospective observational study. In the first part of the study, consenting eligible adult patients with low risk papillary thyroid cancer that is confined to the thyroid, are provided verbal and written information about their disease and the option of active surveillance (close monitoring with intention to treat if disease progresses or if the patient changes her/his mind), as an alternative to thyroid surgery (thyroidectomy - traditional standard of care). Patients are free to make their own disease management choice (ie. active surveillance or thyroidectomy) and the investigators are examining how often patients choose each of these options. The investigators are also examining the reasons for their choice. In the second part of the study, consenting, eligible patients who completed the preceding part of the study and chose either a) active surveillance, or b) thyroid surgery, are tracked with respect to clinical and psychosocial outcomes as well as quality of life. Patients who chose active surveillance are free to change their mind and have surgery at any point, even if the disease does not progress. The primary study outcome is decision regret at one year, in the respective groups of patients who chose active surveillance or thyroidectomy.

Detailed Description
-----------------
This is a prospective observational study, consisting of multiple parts. In the first part of the study, eligible, consenting adult patients with low risk papillary thyroid cancer who have not had thyroid surgery, are provided with verbal and written information about the disease prognosis, surgical treatment outcomes, and the option of active surveillance (close monitoring with the intention of treatment if there is disease progression or if the patient changes her/his mind), as an alternative to immediately proceeding with thyroidectomy. The primary outcome of this part of the study is the final disease management decision of the patient (ie. active surveillance or thyroid surgery) and we are also examining patients' reasons for their choice. In the second part of this study, eligible consenting patients who completed the preceding part of the study and chose either: a) active surveillance, or b) thyroid surgery, are tracked with respect to disease, treatment, psychosocial outcomes, and quality of life. For patients under active surveillance, clinical follow-up is conducted at a participating study institution. For patients who choose surgery, surgery and related clinical follow-up may be performed at any institution (of the patient's choice), however, the thyroid cancer-related medical records are regularly reviewed. Questionnaires are mailed to patients at one year. The primary outcome for this study is decision regret (on the decision for active surveillance or surgery) at one year after initiating the disease management decision (ie. active surveillance or surgery). As the decision for surgery or active surveillance is up to the patient and the proportion of patients in each group is unknown, the results in respective groups will be reported separately for the primary analysis (and only compared if sufficient numbers are available in each group).

Official Title
-----------------
Deciding on Active Surveillance as an Alternative Option to Surgery in the Primary Management of Low Risk Papillary Thyroid Cancer

Conditions
-----------------
Thyroid Cancer Stage I

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients 18 years of age or older Newly diagnosed previously untreated papillary thyroid cancer (PTC) (fine needle aspiration biopsy positive for PTC or suspicious for PTC). PTC must be less than 2 cm in maximal diameter on thyroid ultrasound No evidence of metastatic cervical lymphadenopathy on ultrasound imaging of the neck (or other neck imaging) and no known distant metastatic thyroid cancer. No other absolute indications for thyroid or parathyroid surgery Permission for review of thyroid cancer-related medical records Exclusion Criteria: Regional or distant metastatic thyroid cancer History of prior thyroid cancer surgery High risk location of the PTC (e.g. adjacent to the recurrent laryngeal nerve or trachea) The patient has clinical signs, imaging, or indirect laryngoscopy findings suggestive of locally advanced thyroid cancer (i.e. vocal cord paralysis or any clinical or radiographic signs of extrathyroidal invasion into adjacent structures such as the strap muscles of the neck, trachea or esophagus) Known or suspected poorly differentiated or non-papillary thyroid cancer Medically unfit for surgery due to co-morbidity Another active malignancy with limited life expectancy of < 1 year. Pregnancy at the time of study enrollment. Other absolute indication for thyroid or parathyroid surgery Unable to provide informed consent for the study or comply with study follow-up procedures due to current severe active cognitive or psychiatric impairment, substance abuse, or other reasons.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active surveillance<br>Patients under active surveillance choose to not have immediate thyroidectomy. Patients are closely monitored with respect to clinical status, ultrasound imaging, biochemical indices (thyroid function, thyroglobulin, and thyroglobulin antibodies) and any thyroid cancer-related treatments (if needed). Active surveillance is conducted at a participating study site. Criteria defining disease progression are established, and if such criteria are met, thyroid surgery is recommended to the patient. However, patients are free to choose to have thyroid surgery at any time, in the absence of disease progression. Thyroid cancer clinical and treatment outcomes are tracked by the study team. | |
| Immediate Surgery<br>Patients who choose surgery, undergo thyroidectomy, as per current standards of care, by a surgeon of their choice in an institution of their choice. The treating surgeon, in discussion with the patient, will choose the extent of thyroid surgery that may be appropriate for the individual case. Post-surgical follow-up is per the discretion of the treating surgeon, endocrinologist, or other healthcare providers involved in the patient's thyroid cancer care. Thyroid cancer clinical and treatment outcomes are tracked by the study team. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease management decision (first part of the study, focused on treatment management choice) | In the first part of the study, at any time point after study enrollment and receiving written and verbal information about disease prognosis and the option of active surveillance, patients will be asked to provide a final disease management decision (active surveillance or surgery). This decision should be generally finalized within 3 months of enrollment in the study. | 0 to 3 months after enrollment in the study (as it is expected that the disease management decision should be completed within that time frame) | 
| Decision regret (second part of the study - follow-up of respective active surveillance and surgical patient groups) | Decision regret (total score, self-administered written questionnaire) | 1 year after enrolling in the second phase of the study (i.e. one year after enrolling in the active surveillance arm or 1 year after the first thyroid cancer surgery) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease management decision rationale/explanation | Patients will be asked the reason for choosing active surveillance or surgery once final decision is complete for the disease management plan (i.e. active surveillance or surgery). Each patient will be asked, in a semi-structured interview question, to explain the reason why the disease management strategy that was chosen. The results will be coded and analyzed using a mixed methods approach. | 0 to 3 months after enrollment in the study, once the decision on disease management is finalized (it is expected that the disease management decision should be completed within the time frame of 0 to 3 months) | 
| Disease management decision-maker identification | Patients will be asked about the extent of their involvement in disease management decision-making | 0 to 3 months after enrollment in the study, once the decision on disease management is finalized (it is expected that the disease management decision should be completed within the time frame of 0 to 3 months) | 
| Disease management decision satisfaction | Satisfaction with decision scale (overall score) | 0 to 3 months after enrollment in the study, once the decision on disease management is finalized (it is expected that the disease management decision should be completed within the time frame of 0 to 3 months) | 
| Baseline coping mechanisms in all patients and respective study groups | Brief Cope Questionnaire (description of all respective subscales per the questionnaire developer) | Within 1 month of study enrollment (baseline interview after enrollment in the study, prior to being provided detailed information about active surveillance) | 
| Baseline evaluation of fear of disease progression in all patients and respective study groups (i.e. those who ultimately choose active surveillance or surgery) | Short form of the Fear of Progression Questionnaire (overall score) | Within 1 month of study enrollment (baseline interview after enrollment in the study, prior to being provided detailed information about active surveillance) | 
| Fear of disease progression at 1 year follow-up - in respective study groups (active surveillance or surgery) | Short form of the Fear of Progression Questionnaire (overall score) | 1 year after enrolling in the second phase of the study (i.e. one year after enrolling in the active surveillance arm or 1 year after the first thyroid cancer surgery) | 
| Baseline evaluation of surgical fear in all patients and respective study groups (i.e. those who ultimately choose active surveillance or surgery) | Surgical Fear Questionnaire (total score) | Within 1 month of study enrollment (baseline interview after enrollment in the study, prior to being provided detailed information about active surveillance) | 
| Baseline evaluation of decision self-efficacy in all patients and respective study groups (i.e. those who ultimately choose active surveillance or surgery) | Decision Self-Efficacy Scale (total score) | Within 1 month of study enrollment (baseline interview after enrollment in the study, prior to being provided detailed information about active surveillance) | 
| Psychological distress at 1 year in respective study groups | Hospital Anxiety and Depression Scale (respective total scores for anxiety and depression, respectively) | 1 year after enrolling in the second phase of the study (i.e. one year after enrolling in the active surveillance arm or 1 year after the first thyroid cancer surgery) | 
| Disease-specific quality of life at 1 year | M.D. Anderson Symptom Inventory (respective Symptom Severity and Symptom Interference with life - respective total scores for these subscales) | 1 year after enrolling in the second phase of the study (i.e. one year after enrolling in the active surveillance arm or 1 year after the first thyroid cancer surgery) | 
| Body image perception at 1 year | Body Image Scale (overall score) | 1 year after enrolling in the second phase of the study (i.e. one year after enrolling in the active surveillance arm or 1 year after the first thyroid cancer surgery) | 
| Thyroid cancer surgery in patients who initially choose active surveillance | The number and percent of patients who initially choose active surveillance, but go on to have surgery (with surgical indication) will be evaluated yearly | From date of enrollment in the active surveillance arm of the study until the date of first documented thyroid cancer surgery or date of death from any cause, whichever comes first, assessed up to 10 years from active surveillance arm study enrollment | 
| Disease progression | Structural disease progression (Defined as follows: primary tumor growth >3 mm in largest diameter in the active surveillance group, or new metastatic disease in either the active surveillance or surgical group, or newly diagnosed thyroid cancer in the thyroid bed/remaining thyroid lobe in the surgical group) | From date of enrollment in the active surveillance or surgical arms of the study until the date of first documented thyroid cancer structural disease progression or death from any cause, whichever comes first, assessed up to 10 years from enrollment | 
| Thyroid surgical complications | Any thyroid surgical complications (defined as hypoparathyroidism, recurrent laryngeal nerve injury, or other surgical complications documented in the medical record) will be ascertained in all patients from either group, who undergo thyroid surgery | From date of enrollment in the active surveillance or surgical arms of the study until the date of any documented thyroid cancer surgical complication or death from any cause, whichever comes first, assessed up to 10 years from enrollment | 
| New chronic prescription thyroid hormone use | New chronic prescription thyroid hormone use will be ascertained in both study arms. Individuals who are taking chronic prescription thyroid hormone prior to enrollment in the study will be excluded from this analysis. | From date of enrollment in the active surveillance or surgical arms of the study until the date of first documented prescription thyroid hormone use or death from any cause, whichever comes first, assessed up to 10 years from enrollment | 
| Healthcare resource utilization | Thyroid cancer or thyroid cancer care-related expenses/procedures will be ascertained in both study arms including thyroid cancer surgery, thyroid hormone use, thyroid cancer-related diagnostic testing [bloodwork, imaging], thyroid biopsies, other thyroid cancer-related procedures, thyroid cancer-related specialist healthcare provider visits, radioactive iodine treatment or scans, use of recombinant human thyrotropin, or healthcare expenditures for treatments of complications of thyroid surgery [e.g. prescription treatments for hypoparathyroidism]). | From the date of enrollment until death from any cause or up to 10 years from enrollment | 
| Serum thyroglobulin measurement in the active surveillance group | Serum thyroglobulin (with thyroglobulin antibody) measurement | Upon enrollment in the active surveillance arm of the study and thereafter every 6 months for 2 years, and thereafter yearly, for up to 10 years, for patients in the active surveillance arm of the study (who do not have surgery) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
papillary thyroid cancer, thyroidectomy, active surveillance