Evaluating the risk of re-recurrence in patients with persistent/recurrent thyroid carcinoma after initial reoperation

Abstract

Background

Although the 2015 American Thyroid Association guidelines proposed initial and response-to-therapy risk stratifications were adequately validated in untreated papillary thyroid cancer patients, it is still unknown how they work in persistent/recurrent papillary thyroid cancer patients. This study aimed to evaluate and revise the stratifications in these patients.

Methods

This retrospective study included patients who received the first reoperation with complete thyroid resection but without radioactive iodine ablation. Stratifications were performed considering the persistent/recurrent tumor characteristics and thyroglobulin levels 1 to 6 months after reoperation and then revised with new prognostic factors and adjusted thyroglobulin cutoff values, respectively. Prognostic performance was evaluated with Kaplan-Meier curves, proportion of variation explained, and Harrell’s concordance index.

Results

Among a total of 232 patients, 5-year re-recurrence free survival rates were 92.4%, 86.2%, and 74.5% in low-, intermediate-, and high-risk patients, respectively (all P > .05) and 97.0%, 96.3%, and 81.6% in excellent response, intermediate response, and biochemical incomplete response groups, respectively (excellent response versus intermediate response, P > .05; intermediate response versus biochemical incomplete response, P < .05). After incorporating age at reoperation, recurrent primary size, and recurrent lymph node number, the high-risk group had significantly compromised re-recurrence free survival versus the intermediate-risk group (76.2% vs 91.6%). After adjusting thyroglobulin values, 5-year re-recurrence free survival rates were 96.4%, 85.9%, and 75.8% in excellent response (<1 ng/mL), intermediate response (1–10 ng/mL), and biochemical incomplete response (≥10 ng/mL) groups, respectively (all P < .05), with a higher proportion of variation explained (12.8% vs 10.1%) and concordance index (0.669 vs 0.615) compared with the American Thyroid Association version.

Conclusion

The revised American Thyroid Association initial and response-to-therapy risk stratifications have acceptable predictive value for persistent/recurrent papillary thyroid cancer patients.

Introduction

Papillary thyroid carcinoma (PTC) is the most common histological subtype of all thyroid cancers. Despite the low mortality rate, persistent/recurrent disease is found in 5% to 20% of PTC patients after initial therapy.¹ Moreover, re-recurrence occurs in a considerable number of patients who undergo reoperation for persistent/recurrent PTC.^2,3

To date, the prognosis of untreated PTC patients has been intensively investigated.⁴ The 2015 American Thyroid Association (ATA) guidelines classified patients without structurally identifiable disease after initial therapy into low-, intermediate-, and high-risk for recurrence. Moreover, additional data including biochemical and imaging findings that are obtained during follow-up have been used to further refine the initial risk estimates.¹ The above stratification systems were adequately validated in cohorts of PTC patients after initial surgery. However, due to the paucity of data, the clinical outcomes of persistent/recurrent disease remain unclear. Furthermore, the initial extent of disease, tumor behavior, and recurrent patterns are extremely different, and the management strategies for persistent/recurrent PTC vary greatly among institutions.^5,6 It is still unknown whether the ATA initial risk stratification and response to therapy stratification systems work well in patients with persistent/recurrent PTC.^4,7,8 According to recent studies, several risk factors for re-recurrence in persistent/recurrent PTC have been recognized, such as age at reoperation, aggressive histology, location and size of the recurrent lesions, gross extrathyroidal extension (gETE), extranodal extension, and so on.9, 10, 11 However, most of these studies had a small sample size, and varied risk factors without consistency were found.

In this study, we analyzed persistent/recurrent PTC patients treated at a single tertiary care institution to identify the risk factors for re-recurrence and the serum thyroglobulin (Tg) levels after first reoperation and demonstrated how the ATA initial risk stratification and response to therapy stratification systems work in these patients.