Increase in Aggressive Papillary Thyroid Carcinomas Calls for Tailored Therapies

Based on a disproportionate increase in aggressive papillary thyroid carcinomas (PTCs), researchers stress the importance of therapies tailored specifically for these distinct disease subtypes (JAMA Oncol. 2020 Mar 5. Epub ahead of print).

“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,” explained Allen S. Ho, MD, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California, and co-investigators.

Using data from hospital- and population-based US cancer registries spanning 2000 to 2016, Dr Ho et al sought to assess the incidence, clinicopathologic characteristics, and outcomes of aggressive PTC variants.

These PTC variants included diffuse sclerosing (DSV), tall-cell (TCV), insular, and poorly differentiated (PDTC) subtypes, and were compared against WDPTC and anaplastic cases between January 2019 and October 2019.

The weighted least-squares method was used to calculate age-adjusted incidence via annual percentage change (APC), and Cox regression was used to assess overall and disease-specific survival.

In addition, Dr Ho and colleagues used propensity-score matching to accommodate for clinical and demographic covariates.

Overall, a collective total of 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.

Findings showed a considerable increase in aggressive variant incidence (APC, 9.1; 95% CI, 7.33-10.89; P <.001), ultimately exceeding the relative increases documented in patients with 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,” the investigators reported.

Rates of survival at 10 years in WDPTC, DSV, TCV, PDTC, insular variant, and anaplastic cases were 85.4% (95% CI, 84.6%-86.3%), 79.2% (95% CI, 73.6%-85.3%), 71.9% (95% CI, 68.4%-75.6%), 45.1% (95% CI, 40.2%-50.6%), 27.9% (95% CI, 20.0%-38.9%), and 8.9% (95% CI, 7.5%-10.6%), respectively (P <.001).

Even when adjustments were made for inherent differences in baseline characteristics, these differences largely persevered via multivariable Cox regression and propensity-score matching.

“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,” Dr Ho and co-investigators reported.

“Given increasing prevalence and disparate outcomes, further investigation to identify optimal therapeutic strategies is needed in these diverse, understudied populations,” they concluded.—Hina Porcelli