A histo-clinical score to predict evolution to radioactive iodine-refractory of the follicular cell-derived thyroid carcinoma (PREDIRAIR): a single-centre, prospective, cohort study

Background Radioiodine refractory (RAIR) non-anaplastic follicular-cells derived thyroid carcinomas (FCDTC), are responsible for most FCDTC mortality. Although early detection could enable personalised strategies, precise risk factors are largely unknown. We aimed to search for clinical and histopathological predictive factors available at diagnosis for RAIR evolution. Methods In this single-centre cohort study, patients treated between 2009 and 2018 for a pT3, pT4 or M1 FCDTC (2010 TNM classification), were prospectively enrolled after thyroidectomy. Updated centralised histological review was performed, and a Cox model was used to explore time to RAIR disease. The final multivariable model was then transformed into a 16-point score. Findings Histopathological review identified 28 patients with low-risk neoplasms and 225 with FCDTC. The median follow-up for FCDTC was 8·3 years (95% CI 7·9–8·9), and 40 patients had RAIR- FCDTC (18%). Univariable analyses identified age ≥55 years, stimulated thyroglobulin ≥20 ng/mL at first radioiodine treatment, tumour size, TERT promoter mutation (not BRAF ), un-encapsulated, adipose, muscle and vascular invasion, high Ki67 index, and high-grade follicular cell derived carcinomas (HG-TC) as associated with RAIR evolution at 5 years. On the basis of the final multivariable model with an AUC of 0·90 (0·82–0·97), a 16-point score was constructed: age ≥55 years (hazard ratio 2·05, 95% CI 1·01–4·16; 2 points), stimulated thyroglobulin ≥20 ng/mL at first RAI (5·20, 2·51–10·75; 5 points), TERT promoter mutation (3·22, 1·64–6·33; 3 points), and HG-TC (6·15, 2·86–13·21; 6 points). Interpretation This score allows early identification of patients at risk of RAIR disease. Recent histological category of HG-TC and TERT promoter mutation are the strongest predictive factors. Funding Société Française d'Endocrinologie, Ligue Contre le Cancer.