Response to Letter: What Is the Role of Serum Thyroglobulin Measurement in Patients With Differentiated Thyroid Cancer Treated Without Radioactive Iodine? Free

We thank Dr Giovanella and her colleagues for their interest in our publication (1) and their succinct reminder of the important issues that need to be considered when serum thyroglobulin assays are used in clinical practice. Each of these issues was carefully considered when we published a proposal for a modification of our previously validated response to therapy definitions so that they could be used in patients treated with less than total thyroidectomy and radioactive iodine ablation (2). As with the original response to therapy definitions (3), which have been subsequently validated in multiple studies and endorsed by the American Thyroid Association Guidelines (4), the modified response to therapy definitions (including the thyroglobulin thresholds) were based on literature review and personal experience because adequate prospective studies, which appropriately controlled for all the issues outlined above in these types of patients, were not available.

Our article (1) is simply a validation study to determine if the theoretical definitions we proposed would provide meaningful risk stratification when applied to 2 different cohorts of patients evaluated by clinicians in different countries using different thyroglobulin assays that varied over time with respect to the manufacturer of the assay as well as the functional sensitivity of the assay over time. We made no attempt in this study to “optimize” the actual thyroglobulin thresholds for the definitions precisely because of the reasons that Giovanella and her colleagues outlined in their letter. We agree that future prospective studies done with a single highly sensitive assay over time and controlling for thyroid-stimulating hormone levels, volume of residual disease, extent of surgery, time period after surgery, and many other factors could further optimize the response to therapy definitions.

Nonetheless, we strongly disagree with their conclusions that the response to therapy definitions that we propose “cannot be adopted and safely employed in clinical practice.” Our article clearly shows that, despite all the potential limitations related to serum thyroglobulin assays outlined in their letter, these response-to-therapy definitions do provide a clinically meaningful risk stratification for subsequent outcomes in patients treated with total thyroidectomy without radioactive iodine or with thyroid lobectomy alone. Similarly, the study by Park et al. (5) recently demonstrated that these response-to-therapy definitions were effective in predicting clinical outcomes in a different cohort of patients treated with total thyroidectomy without radioactive iodine or with lobectomy in Asia. Furthermore, the very essence of response to therapy reassessment is continued reevaluation and dynamic risk assessment over time. As a result, the absolute predictive ability of an individual risk estimate at any given point in time is less critical as risk estimates are modified over time as new data become available.

We hope our study will encourage investigators to verify these findings in other cohorts of patients and to further optimize and refine the thyroglobulin threshold limits to provide even better risk estimates as a function of response to therapy in the increasing pool of low-risk thyroid cancer patients being managed with less than total thyroidectomy and radioactive iodine ablation.

Acknowledgments

Disclosure Summary: The authors have nothing to disclose.

References

Author notes