Project description:Objectives In this study, we compared the cost-effectiveness comparison of the active surveillance (AS) and early surgery (ES) approaches for papillary thyroid microcarcinoma (PTMC) from the perspective of the Chinese healthcare system. Methods We performed a cost-effectiveness analysis using a Markov model of PTMC we developed to evaluate the incremental cost-effectiveness ratio of AS and ES. Our reference case was of a 40-year-old woman diagnosed with unifocal (<10 mm) PTMC. Relevant data were extracted after an extensive literature review, and the cost incurred in each state was determined using China Medicare data on payments for ES and AS. The willingness-to-pay threshold was set at ¥242,928/quality-adjusted life-year (QALY) gained. Sensitivity analyses were performed to account for any uncertainty in the model’s variables. Additional subgroup analyses were performed to determine whether AS was cost-effective when different initial monitoring ages were used. Results ES exhibited an effectiveness of 5.2 QALYs, whereas AS showed an effectiveness of 25.8 QALYs. Furthermore, the incremental cost-effectiveness ratio for ES versus AS was ¥1,009/QALY. The findings of all sensitivity analyses were robust. Compared with ES, AS was found to be the cost-effective strategy at initial monitoring ages of 20 and 60 years, with an incremental cost-effectiveness ratio of ¥3,431/QALY and −¥1,316/QALY at 20 and 60 years, respectively. AS was a more cost-effective strategy in patients with PTMC aged more than 60. Conclusions With respect to the norms of the Chinese healthcare system, AS was more cost-effective for PTMC over lifetime surveillance than ES. Furthermore, it was cost-effective even when the initial monitoring ages were different. In addition, if AS is incorporated into the management plan for PTMC in China at the earliest possible stage, a predicted savings of ¥10 × 108/year could be enabled for every 50,000 cases of PTMC, which indicates a good economic return for future management programs. The identification of such nuances can help physicians and patients determine the best and most individualized long-term management strategy for low-risk PTMC.
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:BackgruoundActive surveillance (AS) has been introduced as a management strategy for low-risk papillary thyroid carcinoma (PTC) due to its typically indolent nature. Despite this, the widespread adoption of AS has encountered several challenges. The aim of this systematic review was to evaluate the safety of AS related to disease progression and its benefits compared with immediate surgery (IS).MethodsStudies related to AS in patients with low-risk PTC were searched through the Ovid MEDLINE, Embase, Cochrane Library, and KoreaMed databases. Studies on disease progression, surgical complication, quality of life (QoL), and cost-effectiveness were separately analyzed and narratively synthesized.ResultsIn the evaluation of disease progression, the proportions of cases with tumor growth ≥3 mm and a volume increase >50% were 2.2%-10.8% and 16.0%-25.5%, respectively. Newly detected lymph node metastasis was identified in 0.0%-1.4% of patients. No significant difference was found between IS and delayed surgery in surgical complications, including vocal cord paralysis and postoperative hypoparathyroidism. AS was associated with better QoL than IS. Studies on the cost-effectiveness of AS reported inconsistent data, but AS was more cost-effective when quality-adjusted life years were considered.ConclusionAS is an acceptable management option for patients with low-risk PTC based on the low rate of disease progression and the absence of an increased mortality risk. AS has additional benefits, including improved QoL and greater QoL-based cost-effectiveness.
Project description:The indolent nature and favorable outcomes associated with papillary thyroid microcarcinoma have prompted numerous prospective studies on active surveillance (AS) and its adoption as an alternative to immediate surgery in managing low-risk thyroid cancer. This article reviews the current status of AS, as outlined in various international practice guidelines. AS is typically recommended for tumors that measure 1 cm or less in diameter and do not exhibit aggressive subtypes on cytology, extrathyroidal extension, lymph node metastasis, or distant metastasis. To determine the most appropriate candidates for AS, factors such as tumor size, location, multiplicity, and ultrasound findings are considered, along with patient characteristics like medical condition, age, and family history. Moreover, shared decision-making, which includes patient-reported outcomes such as quality of life and cost-effectiveness, is essential. During AS, patients undergo regular ultrasound examinations to monitor for signs of disease progression, including tumor growth, extrathyroidal extension, or lymph node metastasis. In conclusion, while AS is a feasible and reliable approach for managing lowrisk thyroid cancer, it requires careful patient selection, effective communication for shared decision-making, standardized follow-up protocols, and a clear definition of disease progression.
Project description:ImportanceActive surveillance is sometimes considered as a disease management option for individuals with small, low-risk papillary thyroid carcinoma.ObjectiveTo assess whether patient age is associated with progression of low-risk papillary thyroid carcinoma (tumor growth or incident metastatic disease) in adults under active surveillance.Evidence reviewEight electronic databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Emcare, PsycINFO, Web of Science, and ClincalTrials.gov) were searched from inception to March 2019, supplemented with a hand search. Two investigators independently screened citations, reviewed full-text articles, and abstracted data. Additional data were sought from authors. Random-effects meta-analyses were performed using incidence data (statistically adjusted for confounders and crude rates).FindingsA total of 1658 unique citations were screened, and 62 full-text articles were reviewed, including 5 studies. Three studies included exclusively microcarcinomas and 2 included tumors up to 2 cm in maximal diameter. The mean age of participants was 51.0 to 55.2 years in 4 studies reporting this value. The mean or median follow-up was 5 years or more in 3 studies and approximately 2 years in 2 studies. The pooled risk ratio for tumor growth of 3 mm or more in maximal diameter in individuals aged 40 to 50 years compared with younger individuals was 0.51 when adjusted for confounders (95% CI, 0.29-0.89; 1619 patients, 2 studies), and the unadjusted risk ratio of this outcome for individuals 40 years or older was 0.55 (95% CI, 0.36-0.82; 2097 patients, 4 studies). In adults aged 40 to 45 years, the unadjusted risk ratio for any tumor volume increase compared with younger individuals was 0.65 (95% CI, 0.51-0.83; 1232 patients, 4 studies). The pooled risk ratio for incident nodal metastases in individuals 40 years or older was 0.22 (95% CI, 0.10-0.47; 1806 patients, 3 studies); however, in a secondary analysis, the risk difference was not significantly different. There was no statistically significant heterogeneity in any of the meta-analyses. There were no thyroid cancer-related deaths nor incident distant metastases.Conclusions and relevanceThis study suggests that older age may be associated with a reduced risk of primary papillary thyroid carcinoma tumor growth under active surveillance. Incident metastatic disease is uncommon during active surveillance.
Project description:ImportanceUnlike for prostate cancer, active surveillance for thyroid cancer has not achieved wide adoption. The parameters by which this approach is feasible are also not well defined, nor is the effect of patient anxiety.ObjectiveTo determine if expanded size/growth parameters for patients with low-risk thyroid cancer are viable, as well as to assess for cohort differences in anxiety.Design, setting, and participantsThis prospective nonrandomized controlled trial was conducted at a US academic medical center from 2014 to 2021, with mean [SD] 37.1 [23.3]-month follow-up. Of 257 patients with 20-mm or smaller Bethesda 5 to 6 thyroid nodules, 222 (86.3%) enrolled and selected treatment with either active surveillance or immediate surgery. Delayed surgery was recommended for size growth larger than 5 mm or more than 100% volume growth. Patients completed the 18-item Thyroid Cancer Modified Anxiety Scale over time.InterventionsActive surveillance.Main outcomes and measuresCumulative incidence and rate of size/volume growth.ResultsOf the 222 patients enrolled, the median (IQR) age for the study population was 46.8 (36.6-58) years, and 76.1% were female. Overall, 112 patients (50.5%) underwent treatment with active surveillance. Median tumor size was 11.0 mm (IQR, 9-15), and larger tumors (10.1-20.0 mm) comprised 67 cases (59.8%). One hundred one (90.1%) continued to receive treatment with active surveillance, 46 (41.0%) had their tumors shrink, and 0 developed regional/distant metastases. Size growth of more than 5 mm was observed in 3.6% of cases, with cumulative incidence of 1.2% at 2 years and 10.8% at 5 years. Volumetric growth of more than 100% was observed in 7.1% of cases, with cumulative incidence of 2.2% at 2 years and 13.7% at 5 years. Of 110 patients who elected to undergo immediate surgery, 21 (19.1%) had equivocal-risk features discovered on final pathology. Disease severity for all such patients remained classified as stage I. Disease-specific and overall survival rates in both cohorts were 100%. On multivariable analysis, immediate surgery patients exhibited significantly higher baseline anxiety levels compared with active surveillance patients (estimated difference in anxiety scores between groups at baseline, 0.39; 95% CI, 0.22-0.55; P < .001). This difference endured over time, even after intervention (estimated difference at 4-year follow-up, 0.50; 95% CI, 0.21-0.79; P = .001).Conclusions and relevanceThe results of this nonrandomized controlled trial suggest that a more permissive active surveillance strategy encompassing most diagnosed thyroid cancers appears viable. Equivocal-risk pathologic features exist in a subset of cases that can be safely treated, but suggest the need for more granular risk stratification. Surgery and surveillance cohorts possess oppositional levels of worry, elevating the importance of shared decision-making when patients face treatment equivalence.Trial registrationClinicalTrials.gov Identifier: NCT02609685.
Project description:The adverse effects of overdiagnosis and overtreatment observed in men with clinically insignificant prostate cancers after the introduction of prostate-specific antigen-based screening are now being observed in those with thyroid cancer, owing to the introduction of new imaging technologies. Thus, the evolving paradigm of active surveillance in prostate and thyroid cancers might be valuable in informing the development of future active surveillance protocols. The lessons learned from active surveillance and their implications include the need to minimize the use of broad, population-based screening programmes that do not incorporate patient education and the need for individualized or shared decision-making, which can decrease the extent of overtreatment. Furthermore, from the experience in patients with prostate cancer, we have learned that consensus is required regarding the optimal selection of patients for active surveillance, using more-specific evidence-based methods for stratifying patients by risk. In this Review, we describe the epidemiology, pathology and screening guidelines for the management of patients with prostate and thyroid cancers; the evidence of overdiagnosis and overtreatment; and provide overviews of existing international active surveillance protocols.
Project description:ObjectivesTo assess the diagnostic accuracy of multimodal ultrasound in differentiating anaplastic thyroid carcinoma (ATC) from papillary thyroid carcinoma (PTC) and to evaluate its capability in detecting thyroid carcinoma (TC) aggressiveness.MethodsSixty nude mice were randomly assigned to ATC and PTC groups and injected subcutaneously with KHM-5M and TPC-1 cell lines, respectively. Tumors were analyzed using B-mode ultrasound (B-US), Color Doppler flow imaging (CDFI), elastography, and contrast-enhanced ultrasound (CEUS). A logistic model integrating multimodal ultrasound data was constructed, and Ki-67 and CD31 expressions in tumor tissues were analyzed immunohistochemically. Correlations between ultrasound features and aggressiveness markers were investigated.ResultsThe ATC group exhibited significantly higher strain-elastography scores (p=0.009) and Adler grades in CDFI (p=0.045). CEUS revealed a higher frequency of heterogeneous enhancement (95.2% vs. 48.1%, p<0.001) and perfusion defects (90.5% vs. 63.0%, p<0.001) in ATC. Model area under the curve (AUC) values for distinguishing ATC from PTC were 0.963 for (B-US + CEUS), 0.926 for CEUS, 0.729 for elastography, 0.663 for CDFI, and 0.675 for B-US. The multimodal ultrasound model demonstrated significant correlations with Ki-67 (p<0.001) and microvessel density (MVD) (p<0.001).ConclusionsMultimodal ultrasound showing high efficacy with an AUC of 0.963 for B-US and CEUS combined in distinguishing ATC from PTC and exhibited strong associations with Ki-67 and MVD. Incorporating multimodal ultrasound, with an emphasis on CEUS, into active surveillance strategies for PTC is recommended. By providing detailed insights into tumor vascularity and aggressiveness, multimodal ultrasound could play a crucial role in early detection and treatment decision-making, improving patient outcomes.
Project description:ObjectiveActive surveillance (AS) has been suggested as a management option for low-risk papillary thyroid microcarcinoma (PTMC). However, the currently proposed selection criteria for AS application do not consider various clinical factors. The purpose of this study was to analyze clinical factors related to recurrence that could be confirmed preoperatively in patients who underwent surgery for PTMC and to identify factors worth considering when deciding whether to apply AS.Materials and methodsData were collected from patients with PTMC who underwent surgical treatment at Chungnam National University Hospital. A retrospective cohort was established according to the presence or absence of recurrence during the follow-up period. In total, 2717 patients were enrolled, of whom 60 experienced recurrence. Various clinical factors that could be identified before surgery were analyzed.ResultsThe relationship between various clinical factors that could be confirmed preoperatively and recurrence was confirmed through Cox regression analysis and Kaplan-Meier curve analysis. BRAF mutation and the tall cell variant were significantly more common in patients with recurrence. In patients aged 55 years or older, the risk of recurrence was lower than in younger patients, while the recurrence-free survival (RFS) rate was higher.ConclusionWhen choosing between surgical treatment or AS in PTMC patients, additional consideration of the patient's clinical factors, such as age and BRAF mutation status, may be required in addition to the existing criteria.
Project description:Background/Objectives: There remain several challenges to the acceptance and standardization of active surveillance (AS) in patients with early thyroid cancer. The purpose of this study was to update the evidence of tumor progression outcomes in AS to support resolution of clinical concerns and to examine the effect of follow-up duration, period context such as diagnostic techniques, and tumor size at baseline on outcomes. Methods: PubMed, Web of Science, and Embase were used to search for original articles in English until January 2024. The main outcomes were the pooled proportion of patients who showed tumor growth ≥ 3 mm, metastasis to cervical lymph nodes, and conversion to delayed thyroid surgery. A single-arm meta-analysis was performed using a random-effects model. Results: Fourteen studies with 7291 patients were included in the analysis. Pooled results showed that 5.6% (95% CI: 4.2-7.4) of patients increased tumor diameter by more than 3 mm, 1.1% (95% CI: 0.9-1.4) developed cervical lymph node metastases by clinical diagnosis and 3.6% (95% CI: 3.1-4.2) by pathology, 12.7% (95% CI: 9.9-16.1) of patients converted to delayed surgery, with 31.6% (95% CI: 25.3-38.7) of those conversions being due to tumor progression. Subgroup analysis showed a small difference in the proportion of outcomes by baseline tumor size but no increase in the proportion of tumor progression or conversion to surgery due to other factors. Conclusions: This meta-analysis suggests long-term stability in the proportion of tumor progression in AS and less susceptibility to external influences.