Active Surveillance and Surgery Outcomes in Low Risk Papillary Thyroid Cancer

Recruiting

• Conditions: Papillary Thyroid Cancer; Papillary Microcarcinoma of the Thyroid; Papillary Thyroid Carcinoma

• Registration Number: NCT04624477
• Lead Sponsor: University Health Network, Toronto

Brief Summary

This is a prospective, observational, multi-center study examining the long-term outcomes of patients with small, low risk papillary thyroid cancer who offered the choice of active surveillance (close follow-up to monitor for potential disease progression) or immediate surgery.

Detailed Description

This is a prospective, observational multi-center study, building on an initial single-centre study from Toronto, Canada (ClinicalTrials.gov Identifier: NCT03271892). Adult patients with small, low-risk papillary thyroid cancer may choose either active surveillance (close follow-up with the intention of surgery if the disease progresses or if the patient changes their mind and wants surgery) or immediate thyroid surgery (thyroidectomy). Patients who choose active surveillance are clinically followed at the participating study centre and those who choose surgery, receive usual care from their treating surgeon and/or other thyroid cancer specialists.

Thyroid cancer clinical and treatment outcomes are tracked (by medical record review) at least yearly for up to 10 years after enrollment. Patients are also asked to complete study questionnaires (patient reported outcomes) yearly for up to 5 years.

The underlying assumption in the study is that since patients' disease management goals differ for individuals choosing active surveillance and those choosing surgery, 'successful' disease management is defined differently for these patient groups. For patients choosing active surveillance, successful disease management may be defined by avoiding thyroid surgery for thyroid cancer progression (i.e. thyroid cancer that has grown or spread to other tissues). For patients choosing surgery, the ultimate goal is cure of the thyroid cancer (i.e. no thyroid cancer detected at long-term follow-up).

The primary analysis in this study is a description of how often patients' initial disease management goals are not achieved at long-term follow-up. For this study, 'failure' of disease management is defined as follows: a) in active surveillance group - surgery for disease progression, and b) in the immediate surgery group - requiring additional treatment for persistent or recurrent thyroid cancer (i.e. thyroid cancer that is detected and treated in follow-up). Thyroid cancer clinical and treatment outcomes as well as patient questionnaire outcomes will be reported.

Study Timeline

• Study First Submitted: 2020-10-27
• Study First Submitted QC: 2020-11-05
• Study First Posted: 2020-11-10
• Study Start: 2021-02-03
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-04
• Last Update Posted: 2024-10-08
• Primary Completion: 2034-12-31
• Study Completion: 2034-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 450

Inclusion Criteria

• Patients 18 years of age or older.
• Newly diagnosed previously surgically untreated papillary thyroid cancer (PTC) or suspicious for PTC on fine needle aspiration biopsy of the thyroid. PTC must be < 2 cm in maximal diameter on thyroid ultrasound.
• The absence of metastatic cervical lymphadenopathy or gross extrathyroidal extension of PTC, as confirmed on neck ultrasound imaging.
• The absence of other current absolute indication for thyroid or parathyroid surgery (e.g. severe hyperthyroidism that cannot be controlled medically, large goitre with severe compressive symptoms, or primary hyperthyroidism meeting surgical criteria).

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Exclusion Criteria

• Metastatic thyroid cancer (lymph nodes or distant).
• History of prior thyroid surgery for any indication.
• The primary PTC being on the trachea or immediately adjacent to the recurrent laryngeal nerve, and with progression would be deemed to be at high risk of growth into these critical structures.
• Clinical signs, imaging, or laryngoscopy findings suggestive of locally advanced thyroid cancer (i.e. vocal cord paralysis due to the thyroid cancer or any clinical or radiographic signs of extrathyroidal invasion into adjacent structures such as the strap muscles of the neck, trachea or esophagus).
• Known/suspected poorly differentiated or non-papillary thyroid cancer.
• Medically unfit for surgery due to severe co-morbidity. Severe comorbidity may include another active malignancy with limited life expectancy of < 1 year).
• Pregnancy at the time of study enrollment.
• Unable/unwilling to provide informed consent for the study or comply with study follow-up procedures due to current active physical limitations/medical co-morbidity, cognitive, or psychiatric impairment substance abuse, or other reasons.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Number of Participants in the Active Surveillance Group who Experience 'Failure' of Active Surveillance Disease Management	Through study completion, an estimated average of 3 years	'Failure' of Active Surveillance Disease Management is defined as: surgery for the indication of thyroid cancer that has progressed during study monitoring. Thyroid cancer disease progression under active surveillance includes: a) thyroid cancer enlargement \> 3mm in largest dimension, b) thyroid cancer growth in a location that is concerning (e.g. extension outside of the thyroid, concerning proximity to critical structures such as the trachea or recurrent laryngeal nerve), or c) development of metastatic disease (in lymph nodes or distant organs). The specific type of disease progression will be reported.
Number of Participants in the Surgical Group who Experience 'Failure' of Surgical Disease Management	Through study completion, an estimated average of 3 years	For patients who choose immediate surgery for management of thyroid cancer, the intent of surgery is curative. Thus, 'failure' of surgical disease management is defined by receiving additional treatment for structural thyroid cancer detected at follow-up (i.e. treatment of thyroid cancer detected on imaging or biopsy during follow-up). Additional thyroid cancer treatment may include additional surgery, radioactive iodine, ethanol ablation of lymph nodes, or external beam radiation treatment. The specific treatment used for recurrent or persistent thyroid cancer and the indication for the treatment will be reported.

Secondary Outcome Measures

Name	Time	Method
Description of Quality of Life (Thyroid Cancer-specific)	Through study completion, an estimated average of 3 years	EORTC QLQ-THY34 (all respective scales). All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. All of the scales and single item measures range in score from 0 to 100. A high score for the symptom scales and single items indicates a worse outcome, whereas a high score for the Social Support scale represents a high level of functioning.
Number of Participants who Experience Long-term Complications of Thyroid Surgery	Through study completion, an estimated average of 3 years	For patients who undergo thyroidectomy during the study, the presence of long-term surgical complications (\> 1 year after initial completion of surgery) will be reported. Specific surgical complications that will be tracked include: a) hypoparathyroidism (requiring prescription treatment), or b) recurrent laryngeal nerve injury.
Number of Participants in Respective Thyroid Cancer Disease Status Categories at Last Follow-up	Through study completion, an estimated average of 3 years	The category of thyroid cancer disease status at last follow-up is recorded at least yearly. For patients in the active surveillance arm, disease status categories include: a) alive with no disease progression, b) alive with cross-over to surgery (with indication for surgery, including disease progression or other reason), c) death due to thyroid cancer, or d) death from any cause. For surgical patients and patients who crossed over to surgery from active surveillance, post-surgical disease status categories include: a) alive with no evidence of thyroid cancer structural disease at last follow-up (e.g.. no evidence of thyroid cancer on imaging or biopsy), b) alive with evidence of thyroid cancer structural disease present at last follow-up (i.e. evidence of thyroid cancer on imaging or biopsy), c) death due to thyroid cancer, or d) death from any cause.
Number of Participants in the Active Surveillance Group who Undergo Thyroidectomy During Follow-up	Through study completion, an estimated average of 3 years	The number of participants in the active surveillance group who cross over to thyroidectomy during follow-up (with the specific indication for the thyroidectomy and type of thyroid surgery) will be reported.
Description of Quality of Life (Cancer-specific)	Through study completion, an estimated average of 3 years	EORTC QLQ-C30 (all respective scales). All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. A high score for a functional scale represents a high / healthy level of functioning (better outcome), a high score for the global health status /quality of life represents a better outcome, but a high score for a symptom scale / item represents a worse outcome.
Measure of Anxiety	Through study completion, an estimated average of 3 years	Generalized Anxiety Disorder Screener questionnaire (minimum score 0, maximum score 21, where a higher score indicates a worse outcome)
Measure of Survivor Concerns	Through study completion, an estimated average of 3 years	Assessment of Survivor Concerns questionnaire (Cancer Worry Subscale - minimum score 3, maximum score 12, where a higher score indicates a worse outcome and General Health Worry Subscale - minimum score 2, maximum score 8, where a higher score indicates a worse outcome)
Measure of Decision Regret (relating to the original decision to undergo active surveillance or thyroid surgery).	Through study completion, an estimated average of 3 years	Decision Regret Scale (minimum score 0, maximum score 100, where a higher number indicates a worse outcome)

Trial Locations

Locations (8)

University of Calgary, Cumming School of Medicine; 🇨🇦 Calgary, Alberta, Canada

University of British Columbia; 🇨🇦 Vancouver, British Columbia, Canada

Division chirurgie ORL et cervico-faciale; 🇨🇦 Montreal, Quebec, Canada

Nova Scotia Health; 🇨🇦 Halifax, Nova Scotia, Canada

Lawson Health Research Institute; 🇨🇦 London, Ontario, Canada

University Health Network; 🇨🇦 Toronto, Ontario, Canada

St. Joseph's Healthcare; 🇨🇦 Hamilton, Ontario, Canada

CHU de Québec - Université Laval; 🇨🇦 Québec, Quebec, Canada