Clinical and treatment patterns of advanced and radioiodine-refractory differentiated thyroid cancer. ERUDIT study

Radioiodine-refractory (RR) disease drives morbidity and mortality in advanced differentiated thyroid cancer (aDTC) and yet real-world longitudinal data from the Iberian Peninsula are sparse.

To characterize clinical features, multidisciplinary management, and outcomes of RR-DTC within a multicenter Iberian cohort, and to explore prognostic factors, including the impact of de novo versus recurrent/progressive presentation.

Multicenter, retrospective cohort of adults with aDTC diagnosed in 2007-2012 at 23 Spanish/Portuguese centers, with follow-up until 2017. Baseline demographic and clinical characteristics, local/systemic treatments used, progression-free survival (PFS) on first-line systemic therapy (ST), overall survival (OS) from RR-DTC, and survival prognostic factors were assessed. An exploratory illness-death multistate Markov model complemented Kaplan-Meier analyses for mortality from initial diagnosis. Missing data were not imputed.

Of 213 aDTC patients, 165 (77.5%) met ≥ 1 RR-DTC criterion at any time during their follow-up. At RR-DTC diagnosis, ECOG was recorded in 92/165 (55.8%): 75 (81.5%) ECOG 0-1 and 17 (18.5%) ECOG 2-4. Management included watchful waiting (WW) in 79/165 (47.9%), locoregional therapy in 83/165 (50.3%), and ST in 61/165 (37.0%), predominantly sorafenib. Median PFS on first-line ST was 16.0 months (95% CI 9.2-29.9). Median OS from RR-DTC diagnosis was 4.7 years (3.4-8.0), shorter for de novo aDTC versus recurrent/progressive eDTC (3.0 vs 8.0 years; log-rank p < 0.0001). In multivariable analyses, age < 55 years and WW ≥ 30 months were associated with longer OS, while de novo aDTC and ECOG 2-4 were associated with higher mortality. From initial DTC diagnosis, the multistate model showed higher cumulative mortality for RR-DTC versus non-RR-DTC (HR 3.22; p < 0.001).

In this Iberian cohort, RR-DTC was frequent and often managed within MDTs, with substantial WW use. De novo aDTC and poor performance status were associated with worse survival. Prolonged WW appeared associated with longer OS, but this likely reflects selection and lead/immortal-time biases underscoring the need for prospective validation.