Pronosthyc: Prognostic factors in radioiodine refractory differentiated thyroid cancer with distant metastases, a multicentric study from the French ENDOCAN-TUTHYREF Network

Radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) patients with distant metastases have a heterogeneous prognosis, spanning from indolent to rapidly progressing disease. Our aim is to assess overall survival (OS) in RAI-R DTC patients and to identify the associated prognostic factors. A retrospective multicentric (ENDOCAN-TUTHYREF Network) analysis of consecutive cases of distant metastatic RAI-R DTC, diagnosed between 1990 and 2022, was performed. Survival was estimated using the Kaplan-Meier method and prognostic factors were assessed by Cox's model. Our cohort included 899 patients (52.1% females, median age 65 years [20–90] at RAI-R DTC diagnosis). Median follow-up was 4.8 years [0.1–40.1], primary tumour resection in 95.9%. Histotypes were papillary (55.6%), follicular (12.2%), oncocytic (10.6%) and poorly differentiated (21.6%). Metastases diagnosis was synchronous to primary in 39.4%, macroscopic (>1 cm) in 48.2% and multiple in 83.4% of the cases; 521 (58%) patients were treated with systemic therapies. In 332 (37%) patients, driver mutation status was assessed: 63% BRAFV600E, 29.5% RAS (21% NRAS, 5% HRAS, 3.5% KRAS) mutations and 6% gene fusions (3% RET, 2% NTRK, 1% ALK). After RAI-R DTC diagnosis, median OS was 9.5 years, (5-, 10-year OS rates; 74.8%, 48.1% respectively). Prognostic factors independently associated with worse OS were age ≥55 years (HR = 2.54; 95%CI = 1.84–3.57), multiple metastatic sites (HR = 2.80; 95%CI = 1.80–4.64), macroscopic metastases (HR = 1.98; 95%CI = 1.54–2.55), positive 18 FDG-PET uptake (HR = 2.08; 95%CI = 1.30–3.52), while better OS was associated to primary tumor resection (HR = 0.50; 95%CI = 0.31–0.86), differentiated tumor type (HR = 0.53; 95%CI = 0.41–0.68), metachronous metastatic presentation (HR = 0.64; 95%CI = 0.50–0.82). RAI-R DTC prognosis can be stratified by some simple independent prognostic factors of OS.