Deciding on Active Surveillance or Surgery for Primary Management of Low Risk Papillary Thyroid Cancer (AS-PTC)

• ClinicalTrials.gov Identifier: NCT03271892
• Recruitment Status: Recruiting
• First Posted: September 5, 2017
• Last Update Posted: April 17, 2019
• Sponsor: University Health Network, Toronto
• Collaborators: Ontario Ministry of Health and Long Term Care; Canadian Cancer Society Research Institute (CCSRI)
• Information provided by (Responsible Party): University Health Network, Toronto

Study Description

Brief Summary:

This is a prospective observational study.

1. 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.
2. 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.

Condition or disease
Thyroid Cancer Stage I

Detailed Description:

This is a prospective observational study, consisting of multiple parts.

1. 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.
2. 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).

Study Design

• Study Type: Observational
• Estimated Enrollment: 200 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Deciding on Active Surveillance as an Alternative Option to Surgery in the Primary Management of Low Risk Papillary Thyroid Cancer
• Actual Study Start Date: May 11, 2016
• Estimated Primary Completion Date: May 11, 2026
• Estimated Study Completion Date: December 31, 2026

Groups and Cohorts

Group/Cohort
Active surveillance; 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; 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.

Outcome Measures

Primary Outcome Measures :

1. Disease management decision (first part of the study, focused on treatment management choice) [ Time Frame: 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) ]
   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.
2. Decision regret (second part of the study - follow-up of respective active surveillance and surgical patient groups) [ Time Frame: 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) ]
   Decision regret (total score, self-administered written questionnaire)

Secondary Outcome Measures :

1. Disease management decision rationale/explanation [ Time Frame: 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) ]
   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.
2. Disease management decision-maker identification [ Time Frame: 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) ]
   Patients will be asked about the extent of their involvement in disease management decision-making
3. Disease management decision satisfaction [ Time Frame: 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) ]
   Satisfaction with decision scale (overall score)
4. Baseline coping mechanisms in all patients and respective study groups [ Time Frame: Within 1 month of study enrollment (baseline interview after enrollment in the study, prior to being provided detailed information about active surveillance) ]
   Brief Cope Questionnaire (description of all respective subscales per the questionnaire developer)
5. Baseline evaluation of fear of disease progression in all patients and respective study groups (i.e. those who ultimately choose active surveillance or surgery) [ Time Frame: Within 1 month of study enrollment (baseline interview after enrollment in the study, prior to being provided detailed information about active surveillance) ]
   Short form of the Fear of Progression Questionnaire (overall score)
6. Fear of disease progression at 1 year follow-up - in respective study groups (active surveillance or surgery) [ Time Frame: 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) ]
   Short form of the Fear of Progression Questionnaire (overall score)
7. Baseline evaluation of surgical fear in all patients and respective study groups (i.e. those who ultimately choose active surveillance or surgery) [ Time Frame: Within 1 month of study enrollment (baseline interview after enrollment in the study, prior to being provided detailed information about active surveillance) ]
   Surgical Fear Questionnaire (total score)
8. Baseline evaluation of decision self-efficacy in all patients and respective study groups (i.e. those who ultimately choose active surveillance or surgery) [ Time Frame: Within 1 month of study enrollment (baseline interview after enrollment in the study, prior to being provided detailed information about active surveillance) ]
   Decision Self-Efficacy Scale (total score)
9. Psychological distress at 1 year in respective study groups [ Time Frame: 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) ]
   Hospital Anxiety and Depression Scale (respective total scores for anxiety and depression, respectively)
10. Disease-specific quality of life at 1 year [ Time Frame: 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) ]
    M.D. Anderson Symptom Inventory (respective Symptom Severity and Symptom Interference with life - respective total scores for these subscales)
11. Body image perception at 1 year [ Time Frame: 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 Scale (overall score)
12. Thyroid cancer surgery in patients who initially choose active surveillance [ Time Frame: 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 ]
    The number and percent of patients who initially choose active surveillance, but go on to have surgery (with surgical indication) will be evaluated yearly
13. Disease progression [ Time Frame: 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 ]
    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)
14. Thyroid surgical complications [ Time Frame: 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 ]
    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
15. New chronic prescription thyroid hormone use [ Time Frame: 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 ]
    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.
16. Healthcare resource utilization [ Time Frame: From the date of enrollment until death from any cause or up to 10 years from enrollment ]
    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]).
17. Serum thyroglobulin measurement in the active surveillance group [ Time Frame: 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) ]
    Serum thyroglobulin (with thyroglobulin antibody) measurement

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 100 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Consenting individuals aged 18 years of age or older with papillary thyroid cancer (PTC) who have a primary tumor that is <2cm in maximal diameter, and fine needle aspiration biopsy is positive or suspicious for PTC. The tumor must be confined to the thyroid (no metastatic disease) and not considered in a high risk location (e.g. adjacent to the recurrent laryngeal nerve or trachea). The patient must have no prior surgical treatment for thyroid cancer.

Criteria

Inclusion Criteria:

1. Patients 18 years of age or older
2. Newly diagnosed previously untreated papillary thyroid cancer (PTC) (fine needle aspiration biopsy positive for PTC or suspicious for PTC).
3. PTC must be less than 2 cm in maximal diameter on thyroid ultrasound
4. No evidence of metastatic cervical lymphadenopathy on ultrasound imaging of the neck (or other neck imaging) and no known distant metastatic thyroid cancer.

6. No other indications for thyroid or parathyroid surgery

7. Permission for review of thyroid cancer-related medical records

Exclusion Criteria:

1. Regional or distant metastatic thyroid cancer
2. History of prior thyroid cancer surgery
3. High risk location of the PTC (e.g. adjacent to the recurrent laryngeal nerve or trachea)
4. 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)
5. Known or suspected poorly differentiated or non-papillary thyroid cancer
6. Medically unfit for surgery due to co-morbidity
7. Another active malignancy (excluding non-melanoma skin cancer) for which patients are receiving treatment or are less than 3 years from completing treatment
8. Pregnancy at the time of study enrollment.
9. Other indications for thyroid or parathyroid surgery
10. 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.

Contacts and Locations

Contacts

Contact: Tom Yoannidis; 416-946-4501 ext 2636; Tom.Yoannidis@uhn.ca

Locations

Canada, Ontario

University Health Network; Recruiting

Toronto, Ontario, Canada, M5G 2C4

Contact: Tom Yoannidis 416-946-4501 ext 2636 Tom.Yoannidis@uhn.ca

Principal Investigator: Anna M Sawka, MD, PhD

Principal Investigator: David P Goldstein, MD

Sub-Investigator: Sangeet Ghai, MD

University Health Network; Recruiting

Toronto, Ontario, Canada, M5G 2C4

Contact: Annie M Sawka, MD (416) 340-4800 ext 5886 Annie.Sawka@uhn.ca

Contact: David P Goldstein, MD (416) 946-2301 David.Goldstein@uhn.ca

Principal Investigator: Annie M Sawka, MD

Principal Investigator: David P Goldstein, MD

Sponsors and Collaborators

University Health Network, Toronto

Ontario Ministry of Health and Long Term Care

Canadian Cancer Society Research Institute (CCSRI)

Investigators

• Principal Investigator: Anna M Sawka, MD,PhD; University Health Network, Toronto
• Principal Investigator: David P Goldstein, MD, PhD; University Health Network, Toronto

More Information

Additional Information:

Protocol manuscript - PMID: 29654030 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Sawka AM, Ghai S, Tomlinson G, Rotstein L, Gilbert R, Gullane P, Pasternak J, Brown D, de Almeida J, Irish J, Chepeha D, Higgins K, Monteiro E, Jones JM, Gafni A, Goldstein DP. A protocol for a Canadian prospective observational study of decision-making on active surveillance or surgery for low-risk papillary thyroid cancer. BMJ Open. 2018 Apr 12;8(4):e020298. doi: 10.1136/bmjopen-2017-020298.

• Responsible Party: University Health Network, Toronto
• ClinicalTrials.gov Identifier: NCT03271892 History of Changes
• Other Study ID Numbers: 15-8942
• First Posted: September 5, 2017
• Last Update Posted: April 17, 2019
• Last Verified: April 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided
• Plan Description: We are in discussions with other groups doing active surveillance research, and in future, may share data with such groups. Final plan not yet established.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Thyroid Neoplasms; Thyroid Cancer, Papillary; Thyroid Diseases; Endocrine System Diseases; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Adenocarcinoma, Papillary; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type