A Scoping Review of Patient Health-Related Quality of Life Following Surgery or Molecular Testing for Individuals with Indeterminate Thyroid Nodules
Abstract
:1. Introduction
2. Materials and Methods
3. Result
Quality Adjusted Life Years (QALY) Studies | |||||||||||||
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Author, Year, Country, Journal | Methodology | Study Design | Sample Size | HrQOL Measures | QALY Calculation | Assessment Time Points | Sample Characteristics | Intervention | Aims of the Study | Outcome Measures | Important Results | General Summary | Key Findings |
Lee L et al., 2014, Canada, Journal of Clinical Endocrinology and Metabolism [9] | Microsimulation model of patients for one-year length cycle. | The study utilized a microsimulation model to evaluate the cost-effectiveness of five management strategies for thyroid nodules with atypia of undetermined significance (AUS) cytology. The strategies compared included molecular testing approaches (gene expression classifiers and gene mutation panels) and standard management from both the U.S. and Canadian healthcare perspectives. | The model simulated a cohort of 1,000,000 patients with AUS thyroid nodules to assess lifetime costs and quality-adjusted life years (QALYs). | Health-related quality of life (HrQOL) was measured using QALYs, with utilities (quality of life weights) assigned to different health states based on existing literature. These values ranged from 0 (death) to 1 (perfect health) and were applied in the model to estimate the overall health outcomes of different treatment strategies. |
| The model evaluated outcomes over the patients’ lifetime, with particular emphasis on QALYs measured over time based on complications and disease recurrence. | n = 1 million Age: 54.4 ± 21.3 b % Females: 81.0% | Gene expression testing performed using gene expression classifier (GEC). Gene mutation testing performed using gene mutation panel (GMP). Standard management was considered a diagnostic lobectomy. | To determine the cost-effectiveness of standard management and two diagnostic MTs, singly or in combination, for the atypia of undetermined significance (AUS) cytology of thyroid nodules. | Quality-adjusted life years. | Canadian healthcare system perspective, CAD 2013, mean QALYs (95% CI):
United States third-party payer perspective, USD 2013, Mean QALYs (95% CI):
| QALYs appear to be very similar between surgery and MT, regardless of the perspective taken. |
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Li H et al., 2011, United States, Journal of Clinical Endocrinology and Metabolism [18] | Microsimulation model of patients for five one-year length cycles. | A Markov decision model was developed to evaluate the cost-effectiveness of using a novel molecular test (Afirma Gene Expression Classifier) for indeterminate thyroid nodules. The model analyzed a hypothetical cohort of adult patients using a societal perspective over a 5-year period. | The model used a hypothetical group of adult patients with cytologically indeterminate thyroid nodules. | Health outcomes were measured using quality-adjusted life years (QALYs), with values ranging from 0 (death) to 1 (perfect health). Utilities for different health states were estimated based on existing literature and expert opinion. | The study used microsimulation and time-trade-off methodology to estimate QALYs. The molecular test resulted in a mean QALY of 4.57, compared to 4.50 for current practice, indicating a modest improvement in quality of life. Utility values were drawn from literature and expert estimates, making direct comparability across methods possible, though sensitivity analysis highlighted that variability in some parameters, like test sensitivity, could influence results. | The model assessed outcomes over a 5-year horizon. The QALYs were evaluated annually within this period. | n = 1 million Age: Adults % Females: Not Available | MT using Afirma Gene Expression Classifier. Current practice was considered surgery (i.e., hemithyroidectomy or total thyroidectomy). | To determine the 5-year cost-effectiveness and health outcomes by comparing surgery and MT in patients with indeterminate FNAB from a societal perspective. | Quality-adjusted life years | MT: 4.57 QALY per patient Current practice: 4.50 QALY per patient | MT modestly improved QALY for patients with ITNs compared to surgery. | The molecular test resulted in the following:
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Najafzadeh M et al., 2012, Canada, Value in Health [18] | Patient-level discrete event simulation for 10-year time horizon. | This study employed a patient-level discrete event simulation model to evaluate the cost-effectiveness of a molecular diagnostic test (DX) used in conjunction with fine-needle aspiration biopsy (FNAB) for thyroid nodules. The model compared the outcomes of using DX with current practice (NoDX), over a 10-year time horizon, for two simulated cohorts of 10,000 patients. | The model simulated 10,000 patients with indeterminate FNAB diagnoses to assess the clinical and economic outcomes of using molecular testing compared to current diagnostic practices | Health-related quality of life (HrQOL) was measured using quality-adjusted life years (QALYs). Utility values for different health states (e.g., surgery, radioactive iodine ablation, hypoparathyroidism, recurrent laryngeal nerve injury) were derived from the literature and applied to each patient in the simulation to calculate QALYs. | QALYs were calculated by multiplying the utility value of each health state with the time spent in that state. The study used a six-dimensional health state short form (derived from the SF-36 health survey) to assign utility weights to various outcomes, such as post-surgery recovery and cancer recurrence. The DX strategy was associated with a gain of 0.046 QALYs (95% CI: 0.019–0.078) per patient over a 10-year period, compared to the NoDX strategy. | The model assessed outcomes over a 10-year period, with QALYs and costs discounted at an annual rate of 3%. | n = 10,000 Age: Adults % Females: Not Available | New molecular diagnostic test. Current practice was considered surgery in accordance with TBSRTC guidelines. | To estimate the cost-effectiveness of using a molecular diagnostic (DX) test as an adjunct to FNAB, compared with current practice for initial indeterminate FNAB cytological nodules. | Quality-adjusted life years | MT: 46 QALY per 1000 patient treated QALY Gain = 0.046 QALY (95% CI 0.019–0.078) QALY loss = 0.266 QALY Current practice: QALY loss = 0.306 QALY | MT improved QALY for patient with ITNs compared to surgery. |
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Vriens D et al., 2014, The Netherlands, Journal of Clinical Endocrinology and Metabolism [21] | Microsimulation model of patients for five one-year length cycles | A Markov decision model was used to evaluate the cost-effectiveness of fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) as a diagnostic tool for cytologically indeterminate thyroid nodules. The model compared FDG-PET/CT with diagnostic surgery in all patients and two molecular tests: the gene expression classifier (GEC) and the mutation marker panel (MMP). | The model represented adult patients with indeterminate fine-needle aspiration cytology (FNAC), specifically Bethesda categories III and IV nodules | Quality-adjusted life years (QALYs) were used to measure health-related quality of life (HrQOL) in the study. Utility values were obtained from the literature and expert panels, with adjustments for health states such as post-surgery recovery, surveillance, and complications. | QALYs were calculated over a 5-year time horizon. FDG-PET/CT provided 4.55 QALYs, which was slightly higher than surgery (4.52 QALYs) and comparable to the molecular tests. The study indicated that FDG-PET/CT prevented unnecessary surgeries, which contributed to the modest increase in QALYs. | The model assessed outcomes over a 5-year period, with costs and utilities discounted at 4.0% and 1.5%, respectively. The majority of surgeries and complications occurred within the first few years of the time horizon. | n = 1 million Age: Adults % Females: Not Available | MT using GEC and MMP. Surgery consisting of diagnostic thyroid surgery. | To determine the 5-year cost-effectiveness for FDG-PET/CT implementation in adult patients with indeterminate FNAB cytology compared with surgery and MTs. | Quality-adjusted life years | MT: GEC: 4.556 (95% CI 4.552–4.560) QALY per patient MMP: 4.515 (95% Cl 4.511–4.519) QALY per patient Surgery: 4.516 (95%CI 4.512–4.520) QALY per patient | MT slightly improved QALY for patient with ITN compared to surgery. |
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Pitt SC et al., 2021, United States, Thyroid [20] | This qualitative study involved semistructured interviews with 85 patients diagnosed with papillary thyroid cancer (PTC) or an indeterminate thyroid nodule before undergoing thyroidectomy. The grounded theory methodology was used to develop a conceptual model of patients’ emotional and psychological responses to diagnosis. | Prospective qualitative study | A total of 85 participants were interviewed, including 50 patients with confirmed papillary thyroid cancer (PTC) and 35 patients with indeterminate thyroid nodules (Bethesda III or IV cytology). | This study focused on the emotional and psychological responses of patients, but it did not use a formal health-related quality of life (HrQOL) scale like SF-36 or ThyPRO. Instead, it explored themes like anxiety, fear, and the psychological impact of the diagnosis on patients’ quality of life. | This study did not calculate QALYs. It qualitatively explored patients’ emotional reactions to the diagnosis of thyroid cancer or indeterminate nodules, such as their immediate fear and urgency to “get it out” upon hearing the word “cancer”. | Interviews were conducted before surgery, providing insight into the participants’ emotional responses shortly after receiving their diagnosis. The interviews took place approximately 23.8 days after the initial diagnosis on average. | Total n = 85 ITN n = 35 Total Age: 48 ± 13.5 b Total % Females: 73% | Patients diagnosed with indeterminate thyroid nodules that are expected to undergo surgery within 2 months. | To understand patient experiences surrounding diagnosis of thyroid cancer or an indeterminate FNAB cytology. | Semi Structured interview | Themes identified from patients with ITNs
| Negative emotions and the “get it out” response was observed in patients with ITN about to undergo surgery |
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Tzelnick S et al., 2023, Israel, Journal of Laparoendoscopic & Advanced Surgical Techniques [22] | This was a retrospective review of the database of a tertiary medical center. The study compared quality of life outcomes between two groups of patients who underwent thyroidectomy: those who underwent transaxillary robotic hemithyroidectomy and those who underwent conventional cervical surgery. The ThyPRO (Thyroid-Specific Quality of Life) questionnaire was used to measure quality of life outcomes. | Retrospective cross-sectional study | The cohort consisted of 131 patients, with 63 undergoing robotic hemithyroidectomy and 68 undergoing conventional thyroidectomy. | Health-related quality of life (HrQOL) was measured using the ThyPRO questionnaire, which assesses physical and mental health outcomes in thyroid patients. The study particularly focused on parameters such as anxiety, depression, cognitive function, and sex life impairment. | This study did not calculate QALYs. It focused on comparing postoperative quality of life outcomes between robotic and conventional thyroidectomy using the ThyPRO scores. | The specific time points for QOL assessments are not mentioned in the abstract. Full paper access may be required to clarify when the ThyPRO questionnaire was administered postoperatively. | n = 32 Age: 45 ± 16.29 b % Females: 87.5% | Surgery consisting of transaxillary robotic thyroidectomy and conventional thyroidectomy. | To compare postoperative QOL between patients that underwent transaxillary robotic thyroidectomy or conventional thyroidectomy from 2012 to 2022. | ThyPRO Quality of Life Questionnaire 85-item | Post-surgery Thy-Pro-39 result for cytologically indeterminate thyroid nodule, mean ± SD: Goiter: 9.08 ± 12.05 Hyperthyroidism: 7.03 ± 9.47 Hypothyroidism: 7.42 ± 15.18 Eye symptoms: 5.57 ± 10.68 Tiredness: 26.79 ± 18.19 Cognitive problems: 7.94 ± 16.48 Anxiety: 10.42 ± 18.60 Depression: 9.04 ± 14.94 Emotion: 15.45 ± 15.29 Impaired social life: 3.71 ± 12.29 Impaired daily life: 9.24 ± 14.35 Impaired sex life: 5.86 ± 14.65 Cosmetic complaints: 3.11 ± 7.62 | Notably, patients had more symptoms of tiredness, emotion, and anxiety. |
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MT Studies | |||||||||||||
Schumm MA et al., 2021, United States, Annals of Surgical Oncology [15] | Prospective longitudinal study. | A total of 252 patients were eligible for the study, with 174 completing the ThyPRO-39 QOL assessment. Of these, 124 had benign molecular test results and 50 had suspicious results. | The ThyPRO-39 questionnaire was used to measure health-related quality of life (HrQOL) across multiple domains, including goiter symptoms, anxiety, depression, cognitive complaints, social impairment, and emotional susceptibility. | This study did not calculate QALYs. It focused on evaluating longitudinal QOL changes in different groups (benign vs. suspicious molecular test results) using the ThyPRO-39 scale scores. | Patients were assessed at baseline (within 0–4 months post-FNA), early follow-up (4–12 months), and late follow-up (12–24 months). Postoperative assessments for suspicious molecular test patients occurred a median of 7.6 months after surgery. | n = 174 Age: 56 (44–66) a Percentage of Females: 77% | MT using either Afirma Genomic Sequence Classifier or ThyroSeq v3. | To assess the longitudinal QOL of patients who underwent FNA biopsy with indeterminate cytology (Bethesda III/IV) that are undergoing surveillance after a benign MT result or thyroidectomy after a suspicious MT result. | ThyPRO-39 Administered at three-time points; (1) baseline (0–4 months after FNA), (2) early (4–12 months after FNA), and (3) late (12–24 months after FNA) | MT Thy-Pro-39 result for cytologically indeterminate thyroid nodule, mean ± SD: Goiter: MT benign: (Baseline: 12.0 ± 15.0 + (n = 102), Early: 11.4 ± 11.9 (n = 71), Late: 11.3 ± 13.3 (n = 52)) MT suspicious: (Baseline: 21.1 ± 23.7 (n = 45), Early: 11.1 ± 15.5′ (n = 9), Late: -- ) Anxiety: MT benign: (Baseline: 24.8 ± 17.8 + (n = 102), Early: 19.9 ± 22.1 (n = 71), Late: 20.2 ± 22.8 (n = 52) MT suspicious: (Baseline: 33.9 ± 26.6 (n = 45), Early: 24.6 ± 19.1 (n = 9), Late: --) Depression: MT benign: (Baseline: 24.0 ± 17.8 + (n = 102), Early: 21.6 ± 15.0 (n = 71), Late: 22.4 ± 17.3 (n = 52), MT suspicious: (Baseline: 36.6 ± 22.6 (n = 45), Early: 27.0 ± 15.1 (n = 9), Late: --) Patients with suspicious MTs reported worse symptoms of goiter, anxiety, and depression compared to benign MTs at baseline ( p < 0.05). No difference in symptoms at the early time point. Emotional susceptibility: MT benign: (Baseline: 26.3 ± 19.1 (n = 102), Early: 24.3 ± 19.3 (n = 71), Late: 25.9 ± 20.0 (n = 52)) MT suspicious: (Baseline: 31.8 ± 22.4 (n = 45), Early: 33.0 ± 18.9 (n = 9), Late: --) Impaired social life: MT benign: (Baseline: 14.5 ± 18.6 (n = 102), Early: 13.1 ± 16.5 (n = 71), Late:--) MT suspicious: (Baseline: 19.2 ± 23.0 (n = 45), Early: 11.1 ± 17.2 (n = 9), Late: --) Impaired daily life: MT benign: (Baseline: 10.5 ± 16.4 (n = 102), Early: 9.0 ± 14.8 (n = 71), Late:--) MT suspicious: Baseline: 15.4 ± 21.0 (n = 45), Early: 7.2 ± 9.2 (n = 9), Late: --) Appearance: MT benign: (Baseline: 18.7 ± 23.0 (n = 102), Early: 13.3 ± 19.6′ (n = 71), Late: 14.3 ± 17.6 (n = 52)) MT suspicious: (Baseline: 18.5 ± 21.1 (n = 45), Early: 10.9 ± 19.4 (n = 9), Late: --) Patients with benign MTs have no significant longitudinal changes in QOL outcomes. At baseline to early follow-up, but not late follow-up appearance improved (p = 0.048) | MT, with a benign result has preserved QOL score across all time intervals. MT, with suspicious result has worse QOL score compared to benign result. | Patients with benign molecular test results maintained stable QOL scores over 18 months of ultrasound surveillance, with no significant worsening of anxiety or depression. Patients with suspicious molecular test results who underwent thyroidectomy reported improved QOL post-surgery, particularly in symptoms of goiter, anxiety, depression, and impaired social life. At 8 months postoperatively, the QOL improvements in patients with suspicious molecular results were significant compared to their baseline pre-surgery scores. | |
Wong CW et al., 2020, United States, Endocrine Practice [16] | Prospective cohort study. | A total of 366 patients completed the QOL assessment, out of 825 patients who consented to the study. The final analysis included 332 patients, after excluding those who completed the survey post-surgery. | Health-related quality of life (HrQOL) was measured using the ThyPRO-39, which evaluates domains such as symptoms of goiter, anxiety, depression, and impaired daily life. | This study did not calculate QALYs. It focused on comparing QOL outcomes between patients with benign and suspicious molecular test results using the ThyPRO-39 scale. | The ThyPRO-39 QOL survey was administered after patients received their FNA and molecular test results, with a median time from FNA to survey completion of 57 days. | Total n = 332 ITN n = 58 Age: 54.9 ± 15 b % Females: 82% | MT using either Afirma Gene Expression Classifier or ThyroSeq v2. | To assess the impact of MT results on the QOL of patients with FNA indeterminate cytology (Bethesda III/IV) nodules. | ThyPRO-39 | FNA cytology Thy-Pro-39 results for thyroid nodules, mean (SD): Goiter: Cytologically benign: 13.3 (17.2) Cytologically malignant: 20.6 (20.3) Anxiety: Cytologically benign: 22.5 (23.6) Cytologically malignant: 34.2 (30.5) Depression: Cytologically benign: 27.7 (20.7) Cytologically malignant: 32.1 (17.8) Impaired daily life: Cytologically benign: 12.0 (19.6) Cytologically malignant: 25.8 (28.4) Patients with malignant cytopathology compared to patients with ITN suspicious MT reported more daily life impairment (p = 0.003). No difference in symptoms of goiter, anxiety, or depression. MT Thy-Pro-39 result for cytologically indeterminate thyroid nodule, mean (SD): Goiter: MT benign: 10.4 (12.9) MT suspicious: 20.5 (20.8) Anxiety: MT benign: 22.8 (19.2) MT suspicious: 25.7 (27) Depression: MT benign: 21.0 (14.9) MT suspicious: 33.3 (24.7) Impaired daily life: MT benign: 11.6 (16.6) MT suspicious: 8.3 (16.6) Patients with benign MTs compared to patients with suspicious MT reported fewer symptoms of goiter (p = 0.033) and depression (p = 0.026). No significant differences in symptoms of anxiety or impaired daily life. | MT, with a benign result had consistent QOL score as FNAB cytological benign nodules. MT, with suspicious result has worse QOL score compared to benign result. | There were no significant differences in QOL between patients with benign FNA and patients with indeterminate FNA with benign molecular test results. Patients with suspicious molecular test results experienced significantly worse symptoms of goiter (20.5 vs. 10.4, p = 0.033) and depression (33.3 vs. 21.0, p = 0.026) compared to those with benign molecular test results. No significant differences were found in anxiety or impaired daily life between patients with benign and suspicious molecular test results. |
4. Discussion
Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Brouillette, K.; Chowdhury, R.; Payne, K.E.; Pusztaszeri, M.P.; Forest, V.-I. A Scoping Review of Patient Health-Related Quality of Life Following Surgery or Molecular Testing for Individuals with Indeterminate Thyroid Nodules. Healthcare 2024, 12, 2025. https://doi.org/10.3390/healthcare12202025
Brouillette K, Chowdhury R, Payne KE, Pusztaszeri MP, Forest V-I. A Scoping Review of Patient Health-Related Quality of Life Following Surgery or Molecular Testing for Individuals with Indeterminate Thyroid Nodules. Healthcare. 2024; 12(20):2025. https://doi.org/10.3390/healthcare12202025
Chicago/Turabian StyleBrouillette, Khadija, Raisa Chowdhury, Kayla E. Payne, Marc Philippe Pusztaszeri, and Véronique-Isabelle Forest. 2024. "A Scoping Review of Patient Health-Related Quality of Life Following Surgery or Molecular Testing for Individuals with Indeterminate Thyroid Nodules" Healthcare 12, no. 20: 2025. https://doi.org/10.3390/healthcare12202025
APA StyleBrouillette, K., Chowdhury, R., Payne, K. E., Pusztaszeri, M. P., & Forest, V.-I. (2024). A Scoping Review of Patient Health-Related Quality of Life Following Surgery or Molecular Testing for Individuals with Indeterminate Thyroid Nodules. Healthcare, 12(20), 2025. https://doi.org/10.3390/healthcare12202025