Pre-ablation Stimulated Thyroglobulin as a Predictor of Persistent / Recurrent Differentiated Thyroid Cancer

  • Clin Thyroidol 2022;34:71–74.
  • Background:
    • In the period immediately following thyroidectomy for differentiated thyroid cancer, there is a need to determine the extent of persistent disease and the likelihood of cancer recurrence
    • Predicting the mortality from thyroid cancer is performed using the AJCC/UICC TNM system
    • In order to assess the risk for disease persistence and recurrence, the American Thyroid Association (ATA) guidelines for differentiated thyroid cancer use a variety of indicators that are determined primarily from the surgical pathology
    • In the initial postoperative assessment, the ATA guidelines state that postoperative thyroglobulin (Tg) values suggestive of distant metastases are considered high risk, though the levels that are useful to guide risk determination are not entirely clear
    • The current study is a single-center, retrospective analysis aimed at determining the prognostic significance of pre-ablation stimulated Tg (ps-Tg) levels on prediction of disease persistence / recurrence and its use as a component of the ATA risk-stratification system
  • Methods:
    • Electronic records were collected from 2006 to 2018 at a tertiary care center in China
    • Patients were included in this analysis if they had undergone total thyroidectomy with postoperative radioactive iodine (RAI) ablation therapy and if their surgical pathology results were available
    • All patients were prepared for RAI using thyroid hormone withdrawal
    • Serum thyroid stimulating hormone (TSH), Tg, and thyroglobulin antibody (TgAb) levels were determined immediately prior to RAI administration
    • Patients with TgAb levels greater than 40 IU/ml were excluded
    • Patients were followed for an average of 5 years
    • The initial interaction was 6 to 12 months following RAI therapy
    • Patients with an excellent response to initial therapy (defined using criteria from the 2015 ATA differentiated thyroid cancer guidelines) were seen annually and followed with Tg measurements while taking levothyroxine (LT4) and with neck ultrasonography
    • Additional imaging studies were used if Tg levels were > 1 ng/ml
    • Anything other than an excellent response to initial therapy was counted as disease persistence
    • A receiver operating characteristic (ROC) curve was used to determine the most sensitive and specific levels of ps-Tg that predicted persistent/recurrent disease versus long-term remission
  • Results:
    • Of the 2524 patients included in this analysis, over 26% were classified as high risk for recurrence by ATA criteria, indicating a cohort that included many patients with advanced disease
    • Of the 2524 patients, 69% were women and over 96% had classic variant papillary thyroid cancer (PTC)
    • The average primary tumor size was 1.4 cm, and 85% of patients had documented lymph node metastases
    • Approximately 85% of patients had an excellent response and 15% had persistent or recurrent disease at the end of the study
    • The median ps-Tg level was 2.42 ng/ml (1.87 for those with excellent response and 35.66 for those with persistent/recurrent disease). Based on ROC analysis, a ps-Tg level of 10.1 ng/ml correlated with a sensitivity of 76% and a specificity of 88%, yielding a positive predictive value (PPV) of 53% and a negative predictive value (NPV) of 95%. This NPV remained >90% in all ATA risk categories.When analyzed by ATA risk categories, a ps-Tg cutoff of 10.1 ng/ml was predictive of outcomes. When below this cutoff, the risk of persistent disease decreased from 9.9% to 4.1% in intermediate-risk patients and from 33.1% to 8.5% in high-risk patients. Similarly, a value above the cutoff significantly increased the risk of persistent/recurrent disease even in low-risk patients (3.5–26.7%). The risk increased in high-risk patients, from 33.1% to 69.5%.ConclusionsIn this retrospective institutional analysis, a single preablation stimulated Tg cutoff level of 10.1 ng/ml significantly improved the prediction of disease recurrence/persistence in differentiated thyroid cancer. The use of this cutoff significantly enhanced prediction when incorporated into the 2015 ATA risk stratification model for differentiated thyroid cancer.COMMENTARYAssessing the likelihood of disease persistence and recurrence is extremely important to patients and providers after a diagnosis of cancer. Notwithstand-ing a recent cancer diagnosis, there is a significant amount of anxiety for patients receiving RAI, as many of those selected to receive it typically have lymph node involvement or larger tumor sizes.Disease predictors lack predictive power in the immediate postoperative assessment of intermedi-ate- and high-risk scenarios based on the surgical pathology alone. Several studies have reported that delayed evaluation (i.e., up to a year following RAI ablation) utilizing biomarkers and neck ultrasonog-raphy have better prognostic capabilities (3-5). For a patient, waiting this long can be nerve-wracking. A test to improve the ability to predict recurrence earlier in the postoperative period is desirable.Often, we measure stimulated Tg prior to giving RAI, though there is no clear guidance as to the value above which higher risk for disease persistence is indicated. Moreover, where does this information fit in regard to what is already estimated based on the risk stratification from the 2015 ATA guide-lines? This study was based on a large sample size and used ROC curve analysis to identify 10.1 ng/ml as a preablation Tg level with an NPV of >90%. This study adds to the literature identifying a preablation stimulated Tg <10 ng/ml as a predictor of excellent response to initial treatment (i.e., surgery and RAI ablation) in intermediate- to high-risk patients (6). This is helpful, as prior studies have investigated lower-risk patients or used various Tg cutoff values (7-9). Additionally, the authors determined that the use of preablation Tg values helped to “refine” recurrence estimates within risk categories. Inter-THYROID CANCER Preablation Stimulated Thyroglobulin as a A l e x Te s s n owPredictor of Persistent/Recurrent Differentiated Thyroid Cancer

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