The role of stimulated thyroglobulin in the prognosis of persistent papillary thyroid carcinoma

Abstract

Objective —to study the incidence of regional metastases after radioiodine therapy in the absence of routine prophylactic neck dissection in patients with papillary thyroid carcinoma (PTC), depending on the levels of stimulated thyroglobulin (TG) and its use for predicting disease persistence. Material and methods. Treatment outcomes were investigated for 738 patients (78.2 % female, 21.8 % male; mean age 49.1 ± 11.9 years) with PTC who underwent thyroidectomy with neck dissection of varying volume in medical institutions of Ukraine with further radioiodine therapy. Risk groups are formed according to ATA 2015 recommendations. The stimulated TG testing was conducted in different laboratories in Ukraine and by different methods, but with comparable reference ranges. Statistical calculationswere done woth MSExcel, AtteStat and StatPlus 7 (AnalystSoftInc.), ROCanalysis, Z-test and Fisher-Freeman-Halton exact test.Particle confidence intervals were determined using Wilson method and VassarStats online calculator. Results and discussion. 738 patients were examined, of whom 22.6 %, 47.3 % and 30.1 % were in the low, medium, and high-risk groups. After the 131I therapy and SPECT (single-photon emission computed tomography) incidence of metastases was 19.1 % overall (2.6 % iodine negative), and 10.8 %, 16.3 %, and 29.7 %, respectively, depending on the TG level. Choosing a cut-off threshold for TG = 0.5 ng/ml (without taking into account the risk group) provides a minimum probability of missing metastases (4.96 %, 95 % CI: 2.42—9.89). In total, 148 (20.1 %) patients were identified in the total of 738 subjects with TG stimulated levels < 0.5 ng/ml, of which 7 (0.9 %) had metastasized after 131I. In 590 (79.9 %) patients with TG ≥ 0.5 ng/ml, 134 (18.2 %) had metastases, while in the low-risk group, 18 (10.8 %) had metastases, including 4 (2.3 %/22.2 %) were found to be iodine-negative. In 12 patients in the TG subgroup < 0.5 ng/ml, 4 (0.54 %/2.4 %) cases with metastases were identified, whereas in the TG subgroup ≥ 0.5 ng/ml, 14 (1,90 %/8.38 %). In the intermediate-risk group, 57 (16.33 %) patients had metastases and all of them were in the subgroup with TG ≥ 0.5 ng/ml. Patients with iodine-positive metastases had higher TG values than patients with iodine-negative ones, but the difference was not statistically significant. The highest incidence of metastases was recorded in the high-risk group, in which 66 (8.94 %/29.73 %) were detected. In all risk groups at TG values < 0.5 ng/ml, the detectability of metastases was low and practically independent of risk level (p > 0.05).At TG values ≥ 0.5 ng / ml, the difference in the detection of metastases between subgroups withmetastaticpositive and metastaticnegative were statistically significant: p < 0.05 in the low-risk group and p < 0.001 in the medium- and high-risk groups. Соnclusions. After thyroidectomy without routine neck dissection, the incidence of metastases in whole body 131I scintigraphy and SPECT was relatively high in all stratification risk groups (low — 10.8 %, medium — 16.3 %, high — 29.7 %). An elevated level of stimulated TG can be considered as a predictor of metastasis, which can be used to individualize further tactics for the treatment of patients with PTC. When the cut-off threshold TG = 0.5 ng/ml is selected, the highest sensitivity(0.95) and the predictive value of the negative result (-PV = 0.953) are provided, specificity and overall diagnostic efficiency are 0.236 and 37.26 %, respectively. Almost the same sensitivity and specificity (0.794 and 0.784, respectively) are reached at the cut-off threshold TG = 7.5 ng/ml (DE = 78.59 %). Regardless of the stratification risk groups in patients with stimulated TG up to 0.5 ng/ml, the probability of a false-negative result is 4.96 %, the detection of metastasis is quite low (0.54 %/0 %/0.41 %) and the need for radioiodine therapy is questionable. In patients with low and intermediate risk, postoperative values from 1.0 to 10.0 ng/ml are optimistic, but they do not completely exclude the detection of metastases (the probability of false-negative result is 6.4—24.2 %). With postoperative values of stimulated TG ≥ 10 ng/ml, the likelihood of persistence increases (probability of false-negative result > 26.2 %), which requires additional therapy.