Incidence and Mortality Risk Spectrum Across Aggressive Variants of Papillary Thyroid Carcinoma

Abstract

IMPORTANCE While well-differentiated papillary thyroid carcinoma (WDPTC) outcomes have been well characterized, the prognostic implications of more aggressive variants are far less defined. The rarity of these subtypes has led to their consolidation as intermediate risk for what are in fact likely heterogeneous diseases.OBJECTIVE To analyze incidence, clinicopathologic characteristics, and outcomes for aggressive variants of papillary thyroid carcinoma (PTC). DESIGN, SETTING, AND PARTICIPANTSThis cohort study used data from 2000 to 2016 from hospital-based and population-based US cancer registries to analyze aggressive PTC variants, including diffuse sclerosing (DSV), tall-cell (TCV), insular, and poorly differentiated (PDTC) subtypes. These variants were compared against WDPTC and anaplastic cases. Data analysis was conducted from January 2019 to October 2019.MAIN OUTCOMES AND MEASURES Age-adjusted incidence was calculated via annual percentage change (APC) using the weighted least-squares method. Overall survival and disease-specific survival were analyzed via Cox regression. Propensity-score matching was used to adjust survival analyses for clinical and demographic covariates.RESULTS Collectively, 5447 aggressive PTC variants were identified (including 415 DSV, 3339 TCV, 362 insular, and 1331 PDTC cases), as well as 35 812 WDPTC and 2249 anaplastic cases. Over the study period, a substantial increase in aggressive variant incidence was observed (APC, 9.1 [95% CI, 7.33-10.89]; P < .001), surpassing the relative increases observed in WDPTC (APC, 5.1 [95% CI, 3.98-6.12]; P < .001) and anaplastic cases (APC, 1.9 [95% CI, 0.75-3.05]; P = .003; parallelism P < .007). Survival varied markedly based on histologic subtype, with a wide spectrum of mortality risk noted; 10-year overall survival was 85.4% (95% CI, 84.6%-86.3%) in WDPTC, 79.2% (95% CI, 73.6%-85.3%) in DSV, 71.9% (95% CI, 68.4%-75.6%) in TCV, 45.1% (95% CI, 40.2%-50.6%) in PDTC, 27.9% (95% CI, 20.0%-38.9%) in the insular variant, and 8.9% (95% CI, 7.5%-10.6%) in anaplastic cases (P < .001). These differences largely persisted even after adjusting for inherent differences in baseline characteristics by multivariable Cox regression and propensity-score matching.CONCLUSIONS AND RELEVANCE An upsurge in aggressive PTC incidence was observed at a rate beyond that seen in WDPTC or anaplastic thyroid carcinoma. Moreover, long-term survival outcomes for aggressive PTC subgroups exhibit heterogeneous clinical behavior and a wide range of mortality risk, suggesting that treatment should be tailored to specific histologic subtypes. Given increasing prevalence and disparate outcomes, further investigation to identify optimal therapeutic strategies is needed in these diverse, understudied populations.

Annual Hazard Rate of Recurrence in Middle Eastern Papillary Thyroid Cancer over a Long-Term Follow-Up

“…Risk analysis of tumor recurrence is highly important for the detection of recurrence, especially in PTC patients. In most of the existing studies, risk of recurrence has been analyzed by survival curves rather than using the hazard functions [26,27]. While survival curves only provide information on the cumulative time distribution of recurrence-free rate, hazard functions can depict the recurrence rate at any point in time among the remaining at-risk individuals [28].…”

Management of Clinically Solitary Papillary Thyroid Carcinoma Patients According to Risk-Scoring Model for Contralateral Occult Carcinoma

“…Although the incidence of PTC has increased rapidly in incidence, understanding of PTC has become more and more thorough from the molecular, diagnostic, and prognostic perspectives. According to the 2004 World Health Organization “Thyroid and Parathyroid Diseases and Genetic Classification”, in addition to the most common classic PTC, there are 15 subtypes of PTC, among which highly aggressive PTC variants, such as diffuse sclerosing, tall-cell, insular, and poorly differentiated subtypes, exhibit heterogeneous clinical behavior and a wide range of mortality risk ( 3 ). Fine needle aspiration (FNA) of thyroid nodules can detect different gene mutations and other molecular changes in PTC, and the use of molecular pathways has permitted the development of new targeted therapies for aggressive PTC ( 4 ).…”

<p>Predictive Factors for Level V Lymph Node Metastases in Papillary Thyroid Carcinoma with <em>BRAF</em>^V600E Mutation and Clinicopathological Features</p>

“…1 Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid cancer, influencing the health and quality of life of people worldwide. 2,3 Cervical lymph node metastasis (LNM), a common clinical phenomenon in PTC, is an independent risk factor for local recurrence and PTC-specific mortality. 4,5 Therefore, therapeutic lateral neck dissection (LND) is generally recommended in patients with LNM.…”