The Impact of Pathologically Positive Lymph Nodes in the Clinically Negative Neck: An Analysis of 39,301 Patients with Papillary Thyroid Cancer.

PURPOSE: Management of patients with low-risk papillary thyroid cancer (PTC) with clinically uninvolved lymph nodes (cN0 LNs), but who harbor metastatic central LNs (pN1a), remains unclear. The number of central LNs examined, radioactive iodine (RAI) utilization, and survival were compared across cN0 patients based on pN stage: pN0 (negative) versus pNx (unknown) versus pN1a (pathologically positive). METHODS: Adults with a PTC ≥1 cm who were cN0 preoperatively were compared based on surgical pathology using the National Cancer Data Base (NCDB; 2003-2011), after univariate and multivariate adjustment. Overall survival (OS) was examined using Kaplan-Meier curves, the log-rank test, and Cox proportional hazards modeling. RESULTS: Overall, 39,301 patients were included; median tumor size was 1.9 cm. More LNs were examined for pN1a versus pN0 diagnosis (pN1a median = 5 LNs vs. pN0 median = 2 LNs; p < 0.0001), with a median of two central LNs found to be positive on surgical resection. Compared with pN0, pN1a patients were 78% more likely to receive RAI (odds ratio 1.78, 95% confidence interval [CI] 1.65-1.91; p < 0.0001). After adjusting for receipt of RAI, no difference in OS was observed for pN1a versus pN0 or pNx patients (p = 0.72). Treatment with RAI was associated with improved OS (hazard ratio 0.78, 95% CI 0.62-0.98, p = 0.03), but the effect of RAI did not differ based on pN stage (interaction p = 0.67). CONCLUSION: More LNs were examined for positive versus negative pN diagnosis in patients with cN0 PTC. Unsuspected central neck nodal metastases in cN0 PTC patients are associated with increased RAI utilization, but no survival difference.

Adjuvant radioactive iodine therapy is associated with improved survival for patients with intermediate-risk papillary thyroid cancer.

CONTEXT: Papillary thyroid cancer (PTC) is the most common endocrine malignancy. The long-term prognosis is generally excellent. Due to a paucity of data, debate exists regarding the benefit of adjuvant radioactive iodine therapy (RAI) for intermediate-risk patients. OBJECTIVE: The objective of the study was to examine the impact of RAI on overall survival in intermediate-risk PTC patients. DESIGN/SETTING: Adult patients with intermediate-risk PTC who underwent total thyroidectomy with/without RAI in the National Cancer Database, 1998-2006, participated in the study. PATIENTS: Intermediate-risk patients, as defined by American Thyroid Association risk and American Joint Commission on Cancer disease stage T3, N0, M0 or Mx, and T1-3, N1, M0, or Mx were included in the study. Patients with aggressive variants and multiple primaries were excluded. MAIN OUTCOME MEASURES: Overall survival (OS) for patients treated with and without RAI using univariate and multivariate regression analyses was measured. RESULTS: A total of 21 870 patients were included; 15 418 (70.5%) received RAI and 6452 (29.5%) did not. Mean follow-up was 6 years, with the longest follow-up of 14 years. In an unadjusted analysis, RAI was associated with improved OS in all patients (P < .001) as well as in a subgroup analysis among patients younger than 45 years (n = 12 612, P = .002) and 65 years old and older (median OS 140 vs 128 mo, n = 2122, P = .008). After a multivariate adjustment for demographic and clinical factors, RAI was associated with a 29% reduction in the risk of death, with a hazard risk 0.71 (95% confidence interval 0.62-0.82, P < .001). For age younger than 45 years, RAI was associated with a 36% reduction in risk of death, with a hazard risk 0.64 (95% confidence interval 0.45- 0.92, P = .016). CONCLUSION: This is the first nationally representative study of intermediate-risk PTC patients and RAI therapy demonstrating an association of RAI with improved overall survival. We recommend that this patient group should be considered for RAI therapy.

Appropriate dosing of adjuvant radioactive iodine for differentiated thyroid cancer.

PURPOSE OF REVIEW: The incidence of well differentiated thyroid cancer (WDTC) is increasing in the US population and is now a major public health concern. Although surgery is the mainstay of treatment, radioactive iodine (RAI) is routinely used for adjuvant therapy, remnant ablation, and for the treatment of metastatic disease. Despite excellent prognosis and stable mortality rates, the use of RAI is increasing in many low and intermediate risk WDTC patients without clear indication that it changes the outcome. As a result, the current treatment paradigm has shifted towards a risk-stratified approach. RECENT FINDINGS: Although there is widespread acceptance that RAI improves overall and recurrence-free survival in patients with metastatic disease, controversy remains regarding radioactive remnant ablation use in low and intermediate risk patients. Additional studies have shown that reduced doses of RAI can provide similar rates of remnant ablation and adjuvant therapy in low and intermediate risk patients without adversely affecting the recurrence rates and mortality. SUMMARY: Recent studies suggest potential new paradigms in radioactive remnant ablation dosing and indications for use. Risk stratification is important in determining the proper use and dosing of RAI.