Malignant pleural effusion (MPE) from differentiated thyroid cancer (DTC) is rare and carries poor prognosis. This study evaluated clinical outcomes and the impact of multikinase inhibitor (MKI) therapy in patients with MPE from DTC.

In this retrospective cohort study of 184 DTC patients with lung metastases, 31 (17%) had MPE. After excluding 10 with non-malignant effusion, 174 were analyzed.

Patients with MPE were older (P<0.001) at DTC diagnosis, had higher T stage (P=0.004), developed pleural metastases earlier (P=0.016), and more frequent macro- and polymetastatic lung lesions (P<0.001) than those without MPE. All MPE cases were radioactive iodine-refractory and developed a median of 6.3 years after DTC diagnosis. Symptomatic MPE occurred in 22 patients (71%), all requiring drainage, while 9 (29%) had asymptomatic MPE. Symptomatic MPE was associated with worse overall survival (OS) compared to patients without MPE (adjusted hazard ratio [HR] 4.62, 95% confidence interval [CI] 2.49–8.57, P<0.001). Notably, patients initiating MKI therapy for symptomatic MPE had the worst OS (adjusted HR 9.78, 95% CI 3.52–27.13, P<0.001). Median OS after MPE diagnosis was 13 months. Symptomatic MPE also had worse post-MPE survival compared to asymptomatic MPE (adjusted HR 5.73, 95% CI 1.52–21.52, P=0.009). MKI therapy did not significantly improve OS or progression-free survival after MPE onset.

MPE in DTC patients with lung metastasis indicates poor prognosis, especially when symptomatic. MKI therapy showed limited survival benefits after MPE onset. Early identification and proactive management of patients with high-risk of MPE may improve outcomes.