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Objective
The usefulness of routine calcitonin measurement for early detection of medullary thyroid carcinoma (MTC) in patients with nodular thyroid disease (NTD) has been investigated in various studies. Recently, a Cochrane review has been published on this issue, but a meta-analysis is lacking yet. Therefore, we performed this meta-analysis.
Methods
We performed an electronic search using PubMed/Medline, Embase and the Cochrane Library. Studies assessing the diagnostic accuracy of routine calcitonin measurement for detecting MTC in patients with NDT were selected. Statistics were performed by using Stata software, risk of bias was assessed using Review Manager version 5.3.
Results
Seventeen studies, involving 74,407 patients were included in the study. Meta-analysis, using the bivariate random effects model and the hierarchical summary receiver operating characteristic (HSROC) curve revealed the following pooled estimates: sensitivity 0.99 (95% CI, 0.81–1.00), specificity 0.99 (95% CI, 0.97–0.99), positive likelihood ratio (L+) 72.4 (95% CI, 32.3–162.1), and negative likelihood ratio (L−) 0.01 (95% CI, 0.00–0.23). Meta-regression analysis showed that the threshold of basal calcitonin is an independent factor, but in particular performing stimulation test is not an independent factor.
Conclusions
We showed that routine basal serum calcitonin measurement in the management of patients with thyroid nodules is valuable for the detection of MTC. However, the published cut-off values should be considered and, if applicable, the patients monitored in a wait-and-see strategy by experienced physicians to avoid overtreatment.
German Cancer Consortium (DKTK), Partner site University Hospital Essen, Essen, Germany
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German Cancer Consortium (DKTK), Partner site University Hospital Essen, Essen, Germany
Department of Nuclear Medicine, University Hospital Münster, Münster, Germany
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German Cancer Consortium (DKTK), Partner site University Hospital Essen, Essen, Germany
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German Cancer Consortium (DKTK), Partner site University Hospital Essen, Essen, Germany
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German Cancer Consortium (DKTK), Partner site University Hospital Essen, Essen, Germany
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German Cancer Consortium (DKTK), Partner site University Hospital Essen, Essen, Germany
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Institute of Pathology, University Hospital Essen, University Duisburg-Essen, Essen, Germany
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German Cancer Consortium (DKTK), Partner site University Hospital Essen, Essen, Germany
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German Cancer Consortium (DKTK), Partner site University Hospital Essen, Essen, Germany
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Objective
Recurrence of differentiated thyroid cancer (DTC) is associated with reduced quality of life, and therefore, 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.
