Predictive value of highly sensitive basal versus stimulated thyroglobulin measurement in long-term follow-up of thyroid cancer

Objective: Recurrence of differentiated thyroid cancer (DTC) is associated with reduced quality of life and early identification of patients at risk is urgently needed. Here we investigated the predictive power of various cut-off values of single stimulated thyroglobulin (s-Tg) and single highly sensitive measured, unstimulated thyroglobulin (u-hsTg) measurements close to the end of primary therapy for recurrence-free survival (RFS) in long-term follow-up (>10 years) of patients with DTC.

Methods: In DTC patients with adjuvant radioiodine therapy, we assessed retrospectively u-hsTg (6±3 months before s-Tg measurement) and s-Tg measurements (≤24 months after last radioiodine therapy). Positive predictive (PPV)/negative predictive values (NPV) of various cut-off values (s-Tg: 0.5/1.0 ng/ml; u-hsTg: 0.09/0.2 ng/ml) for patient outcomes as well as additional factors associated with disease development were analyzed.

Results: In total, 175 patients were retrospectively reviewed (tumor recurrence: n=14/complete remission: n=161). Examined cut-off values for s-Tg and u-hsTg showed significant predictive power for RFS (log-rank: all p<0.001). NPV/PPV for s-Tg were 98.6%/36.4%, respectively (0.5 ng/ml cut-off), and 96.7%/42.9%, respectively (1.0 ng/ml cut-off); those for u-hsTg were 97.3%/35.7%, respectively (0.09 ng/ml cut-off), and 95.2%/85.7%, respectively (0.2 ng/ml cut-off). U-hsTg (p<0.001) and patient age (p<0.05) were significantly associated with tumor recurrence. One-third of patients with tumor recurrence in the course initially showed undetectable u-hsTg after completion of primary therapy.

Conclusion: With >10 years of follow-up, both s-Tg and u-hsTg have a comparably high predictive power for RFS, while only u-hsTg was significantly associated with a recurrence event. Serial u-hsTg measurements seem warranted since patients with tumor recurrence during follow-up may have an undetectable tumor marker at baseline.