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 participants: This 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.

Figure 1.. Age-Adjusted Incidence of Thyroid Carcinoma Variants From 2000 to 2016

Significant annual percentage change (APC) was observed for each subtype. A significantly larger APC was also noted in aggressive papillary thyroid carcinoma (PTC) relative to other variants. Pairwise tests of parallelism were performed between aggressive PTC vs well-differentiated papillary thyroid carcinoma (WDPTC), aggressive PTC vs anaplastic variant, and WDPTC vs anaplastic variant. The circles along the dotted lines represent discrete age-adjusted incidence values for a given thyroid variant at a given year.

Figure 2.. Distribution of Clinicopathologic Covariates Across Papillary Thyroid Carcinoma Aggressive Variants

The T stage data are based on American Joint Committee on Cancer 7th Edition staging. N+ indicates node positivity; PDTC, poorly differentiated thyroid carcinoma; WDPTC, well-differentiated papillary thyroid carcinoma.

Figure 3.. Kaplan-Meier Curves Comparing Overall Survival and Disease-Specific Survival Across Aggressive Papillary Thyroid Carcinoma Variants

Well-differentiated papillary thyroid carcinoma (WDPTC) and anaplastic thyroid carcinoma (ATC) cases were included for reference. Disease-specific survival was calculated using Surveillance, Epidemiology, and End Results data, while overall survival was determined using National Cancer Data Base data. PDTC indicates poorly differentiated thyroid cancer.