Dataset Information

A Protocol for a Pan-Canadian Prospective Observational Study on Active Surveillance or Surgery for Very Low Risk Papillary Thyroid Cancer.

ABSTRACT:

Background

The traditional management of papillary thyroid cancer (PTC) is thyroidectomy (total or partial removal of the thyroid). Active surveillance (AS) may be considered as an alternative option for small, low risk PTC. AS involves close follow-up (including regularly scheduled clinical and radiological assessments), with the intention of intervening with surgery for disease progression or patient preference.

Methods

This is a protocol for a prospective, observational, long-term follow-up multi-centre Canadian cohort study. Consenting eligible adults with small, low risk PTC (< 2cm in maximal diameter, confined to the thyroid, and not immediately adjacent to critical structures in the neck) are offered the choice of AS or surgery for management of PTC. Patient participants are free to choose either option (AS or surgery) and the disease management course is thus not assigned by the investigators. Surgery is provided as usual care by a surgeon in an institution of the patient's choice. Our primary objective is to determine the rate of 'failure' of disease management in respective AS and surgical arms as defined by: i) AS arm - surgery for progression of PTC, and ii) surgical arm - surgery or other treatment for disease persistence or progression after completing initial treatment. Secondary outcomes include long-term thyroid oncologic and treatment outcomes, as well as patient-reported outcomes.

Discussion

The results from this study will provide long-term clinical and patient reported outcome evidence regarding active surveillance or immediate surgery for management of small, low risk PTC. This will inform future clinical trials in disease management of small, low risk papillary thyroid cancer.

Registration details

This prospective observational cohort study is registered on clinicaltrials.gov (NCT04624477), but it should not be considered a clinical trial as there is no assigned intervention and patients are free to choose either AS or surgery.

SUBMITTER: Sawka AM

PROVIDER: S-EPMC8237853 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionLow-risk papillary thyroid cancer (PTC) is increasingly being diagnosed throughout the world; yet the mortality risk is low compared with other malignancies. Traditional management includes thyroid surgery, sometimes followed by radioactive iodine and thyroid hormone treatment. Active surveillance (AS) has been proposed as a means to reduce overtreatment of PTC. AS involves close disease follow-up, with the intention to intervene if the disease progresses, or on patient request.Methods and analysisThis is a multiphase prospective observational study. In the first phase of this study, consenting eligible adults with low-risk PTC, that is, <2 cm in maximal diameter, confined to the thyroid and not immediately adjacent to critical structures in the neck, are provided verbal and written information about PTC disease prognosis following surgery or AS. Questionnaires are administered at baseline and after the disease management decision on AS or surgery is finalised. Patients may choose either option (surgery or AS), and the primary outcome is the frequency with which either disease management option is chosen. Secondary outcomes include: rationale for the decision, role of the patient in decision-making and decision satisfaction. In the second phase of the study, consenting eligible adult patients who completed the first study phase may enrol in respective AS or surgery group follow-up studies. The following outcomes are examined 1 year after enrolment in the follow-up phase: decision regret about disease management choice (primary outcome), psychological distress, disease-specific quality of life, fear of disease progression, body image satisfaction, disease progression, crossover to surgery in the AS group, new chronic thyroid hormone use and healthcare resource utilisation.Ethics and disseminationThe University Health Network Research Ethics Board approved this study (ID 15-8942). The results will be published in an open access journal.Trial registration numberNCT03271892; Pre-results.

Project description:Background: Active surveillance (AS) is an alternative to thyroidectomy for the management of low-risk papillary thyroid microcarcinoma (PTMC). However, prospective AS data collected from diverse populations are needed. Methods: This multicenter prospective cohort study enrolled patients from three referral hospitals in Korea. The participants were self-assigned into two groups, AS or immediate surgery. All patients underwent neck ultrasound every 6-12 months to monitor for disease progression. Progression under AS was evaluated by a criterion of tumor size increment by 3 mm in one dimension (3 mm), 2 mm in two dimensions (2 × 2 mm), new extrathyroidal extension (ETE), or new lymph node metastasis (LNM), and a composite outcome was defined using all four criteria. Results: A total of 1177 eligible patients with PTMC (919 female, 78.1%) with a median age of 48 years (range 19-87) were enrolled; 755 (64.1%) patients chose AS and 422 (35.9%) underwent surgery. Among 755 patients under AS, 706 (female 537, 76.1%) underwent at least two ultrasound examinations and were analyzed. Over a follow-up period of 41.4 months (standard deviation, 16.0), 163 AS patients (23.1%) underwent surgery. Progression defined by the composite outcome was observed in 9.6% (68/706) of patients, and the 2- and 5-year progression estimates were 5.3% and 14.2%, respectively. The observed progression rates were 5.8% (41/706) and 5.4% (38/706) as defined by tumor size enlargement by 3 mm and 2 × 2 mm, respectively, and 1.3% (9/706) and 0.4% (3/706) for new LNM and ETE, respectively. No distant metastases developed during AS. In multivariate logistic regression analysis examining variables associated with progression under AS, age at diagnosis <30 years (odds ratio [OR], 2.86; 95% confidence interval [CI], 1.10 - 7.45), male sex (OR, 2.48; 95% CI, 1.47 - 4.20), and tumor size ≥6 mm (OR, 1.89; 95% CI, 1.09 - 3.27) were independently significant. Conclusions: The progression of low-risk PTMC during AS in the Korean population was low, but slightly higher than previously reported in other populations. Risk factors for disease progression under AS include younger age, male sex, and larger tumor size. Clinical trial registration: Clinicaltrials.gov NCT02938702.

Project description:Background: Active surveillance (AS) of small, low-risk papillary thyroid cancers (PTCs) is increasingly being considered. There is limited understanding of why individuals with low-risk PTC may choose AS over traditional surgical management. Methods: We present a mixed-methods analysis of a prospective observational real-life decision-making study regarding the choice of thyroidectomy or AS for management of localized, low-risk PTCs <2 cm in maximum diameter (NCT03271892). Patients were provided standardized medical information and were interviewed after making their decision (which dictated disease management). We evaluated patients' levels of decision-self efficacy (confidence in medical decision-making ability) at the time information was presented and their level of decision satisfaction after finalizing their decision (using standardized questionnaires). We asked patients to explain the reason for their choice and qualitatively analyzed the results. Results: We enrolled 74 women and 26 men of mean age 52.4 years, with a mean PTC size of 11.0 mm (interquartile range 9.0, 14.0 mm). Seventy-one patients (71.0% [95% confidence interval 60.9-79.4%]) chose AS over surgery. Ninety-four percent (94/100) of participants independently made their own disease management choice; the rest shared the decision with their physician. Participants had a high baseline level of decision self-efficacy (mean 94.3, standard deviation 9.6 on a 100-point scale). Almost all (98%, 98/100) participants reported high decision satisfaction. Factors reported by patients as influencing their decision included the following: perceived risk of thyroidectomy or the cancer, family considerations, treatment timing in the context of life circumstances, and trust in health care providers. Conclusions: In this Canadian study, ∼7 out of 10 patients with small, low-risk PTC, who were offered the choice of AS or surgery, chose AS. Personal perceptions about cancer or thyroidectomy, contextual factors, family considerations, and trust in health care providers strongly influenced patients' disease management choices.

Project description:Background: Active surveillance is established as an alternative to surgery for papillary thyroid microcarcinomas, but inclusion criteria and mortality risk for pursuing a nonsurgical approach have not been clearly defined. To gauge the feasibility of expanding active surveillance thresholds, we investigated the effects of increasing size and age on disease-specific survival (DSS) in a large nonoperative thyroid cancer cohort, compared against a matched group of surgical patients. Methods: Papillary thyroid carcinoma patients staged T1-4N0M0 were identified in the Surveillance, Epidemiology, and End Results (SEER) database between 1975 and 2015, stratified by nonsurgical and surgical management. Propensity score matching was performed to adjust for imbalances in covariates. Multivariable models were constructed using restricted cubic splines to model nonlinear relationships of age and tumor size with DSS. Results: Overall, 1453 nonoperative patients and 54,718 surgical patients met the inclusion criteria. Collectively, increasing age and size after certain thresholds independently led to greater differences in DSS between nonsurgical and surgical patients. For younger ages (14-55 years), surgical approach compared with nonsurgical approach was not associated with any difference in the 10-year DSS among 0-4 cm cancers (99.8% vs. 100%, p = 0.470), 4.1-6 cm cancers (98.8% vs. 100%, p = 0.599), or >6 cm cancers (97.3% vs. 100%, p = 0.718). Older patients with larger tumors (>75 years, >6 cm) demonstrated the greatest difference in DSS (48.1% vs. 91.3%, p < 0.001). Similar results were found when applying propensity score matching. For age, restricted cubic spline plots showed minimal relative survival hazard in nonoperative cases beginning after age 60 years, with a change point illustrating acceleration in relative hazard beyond age 72 years. For size, relative survival hazard was observed after 2.0 cm and increased slowly with nodule growth up to an inflection point of 4.5 cm. Beyond this, mortality risk escalated with each additional year without plateau. Conclusions: Increasing age and size lead to progressively greater mortality risk without surgery, but only beyond certain thresholds. We define escalating gradients at which a nonsurgical approach may be deemed appropriate, and beyond which survival benefits from surgery become apparent. Such findings reconcile controversial observations regarding age and size in active surveillance and further reshape evolving treatment paradigms in thyroid cancer.

Project description:ImportanceActive surveillance of low-risk papillary thyroid cancer (PTC) is now an accepted alternative to immediate surgery, but experience with this approach outside of Japan is limited. The kinetics (probability, rate, and magnitude) of PTC tumor growth under active surveillance have not been well defined.ObjectiveTo describe the kinetics of PTC tumor growth during active surveillance.Design, setting, and participantsCohort study of 291 patients undergoing active surveillance for low-risk PTC (intrathyroidal tumors ≤1.5 cm) with serial tumor measurements via ultrasonography at a tertiary referral center in the United States.InterventionActive surveillance.Main outcomes and measuresThe cumulative incidence, rate, and magnitude of the change in tumor diameter or volume, as well as associations with patient and tumor characteristics.ResultsOf the 291 patients, 219 (75.3%) were women; mean (SD) age was 52 (15) years. During a median (range) active surveillance of 25 (6-166) months, growth in tumor diameter of 3 mm or more was observed in 11 of 291 (3.8%) patients, with a cumulative incidence of 2.5% (2 years) and 12.1% (5 years). No regional or distant metastases developed during active surveillance. In all cases, 3-dimensional measurements of tumor volume allowed for earlier identification of growth (median, 8.2 months; range, 3-46 months before increase in tumor diameter). In multivariable analysis, both younger age at diagnosis (hazard ratio per year, 0.92; 95% CI, 0.87-0.98; P = .006) and risk category at presentation (hazard ratio for inappropriate, 55.17; 95% CI, 9.4-323.19; P < .001) were independently associated with the likelihood of tumor growth. Of the tumors experiencing volume growth, kinetics demonstrated a classic exponential growth pattern, with a median doubling time of 2.2 years (range, 0.5-4.8 years; median r2 = 0.75; range, 0.42-0.99).Conclusions and relevanceThe rates of tumor growth during active surveillance in a US cohort with PTCs measuring 1.5 cm or less were low. Serial measurement of tumor volumes may facilitate early identification of tumors that will continue to grow and thereby inform the timing of surveillance imaging and therapeutic interventions.