PSMA Expression in Differentiated Thyroid Cancer: Association With Radioiodine, (18)FDG Uptake, and Patient Outcome

Context Little is known about prostate-specific membrane antigen (PSMA) expression in patients with cervical involvement of differentiated thyroid cancer (DTC). Objective We investigated PSMA expression in neck persistent/recurrent disease (PRD) using immunohistochemistry and the association with radioiodine (RAI) or 18-fluorodeoxyglucose ((18)FDG) uptake, and patient outcome. Design, Setting, and Patients Data from 44 consecutive DTC patients who underwent neck reoperation from 2006 to 2018 in a comprehensive cancer center. Main Outcome Measure(s) Immunostaining was performed with vascular endothelial marker CD31 and PSMA. PSMA expression was quantified using the immunoreactive score (IRS). RAI and (18)FDG uptake were assessed before surgery using posttherapeutic RAI scintigraphy and (18)FDG positron emission tomography with computed tomography. Mean follow-up after reintervention was 6.5 +/- 3.7 years. Results Thirty patients (68%) showed at least 1 PSMA-positive lesion (IRS >= 2) with similar proportions in RAI-positive and RAI-negative patients (75% vs 66%). In RAI-negative patients, however, the proportion of PSMA-positive disease (79% vs 25%, P < 0.01) and the mean IRS (4.0 vs 1.0, P = 0.01) were higher in (18)FDG-positive than in (18)FDG-negative patients. Furthermore, mean IRS was higher in patients >= 55 years, large primary tumors (>40 mm) or aggressive subtypes, and was correlated with structural disease at last follow-up. Strong PSMA expression (IRS >= 9) was associated with shorter progression-free survival (PFS). Conclusions Our findings show that PSMA expression was present in two-thirds of patients with neck PRD, that it was related to poor prognostic factors and that very high expression was associated with poorer PFS. This preliminary study may offer new perspectives for the management of RAI-refractory DTC.