Diffuse sclerosing variant papillary thyroid carcinoma has worse survival than classic papillary thyroid carcinoma: a meta-analysis

Abstract

Diffuse sclerosing variant of papillary thyroid carcinoma (DSV) is a rare form of thyroid cancer that demonstrates more aggressive histopathology than classical papillary thyroid cancer (c-PTC) however if this leads to worse survival is debated. Many DSVs are driven by fusion events which is of recent clinical importance due to the advent of targeted RET inhibitors. A systematic search and meta-analysis of the literature was preformed to compare outcomes of disease-specific mortality (DSM), metastatic and recurrent disease and the incidence of fusion events between DSV and c-PTC to July 2022. The Newcastle-Ottawa Quality Assessment studies was used to assess quality. An odds ratio (OR) was utilised to measure outcomes with 95% confidence intervals (CI). The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline was followed. Seventeen studies were included with 874 DSV patients compared to 76,013 c-PTC patients. DSV patients had worse DSM, OR=2.50 (95% CI 1.39-4.51), presented with a higher rates of metastatic lymph nodes OR 5.85 (95% CI 2.73-12.53) and more distant metastases, OR 3.83 (95% CI 2.17-6.77). DSV patients had higher odds of recurrent disease, OR 3.23 (95% CI 2.00-5.23) and overall distant metastasis, OR 2.70 (95% CI 1.74-4.17). Rates of RET fusion alterations for DSV ranged from 25-83%. DSV has a worse prognosis than c-PTC with higher rates of recurrent disease and distant metastasis. The high prevalence of RET fusions offers the potential to improve outcomes for patients with DSV.