Prognostic impact of incomplete surgical clearance of radioiodine sensitive local lymph node metastases diagnosed by post-operative 124I-NaI-PET/CT in patients with papillary thyroid cancer

Objectives Nodal involvement is an independent risk factor of recurrence in papillary thyroid cancer (PTC). Neither the international guidelines nor recently introduced ongoing risk adaptation concept consider the extent of initial surgical clearance of radioiodine sensitive lymph node metastases in their stratification systems. We investigated the prognostic relevance of incomplete surgical clearance in patients with purely lymphogeneous metastatic PTC (pN1 M0) despite successful radioiodine ablation. Accurate assessment of pre-ablative nodal status was attempted using PET/CT studies with both 124I-NaI and 18F-FDG along with high-resolution cervical ultrasound.

Methods 65 patients with histologically diagnosed lymph node metastases (pN1 M0) were retrospectively analyzed. Patients with iodine-negative lymph node metastases diagnosed by 18F-FDG PET/CT or distant metastases were excluded from the analysis. The association of disease recurrence with the pre-ablative nodal status, as well as other baseline characteristics was examined applying nonparametric tests for independent samples and multiple regression analysis. Patients with persistent lymph node metastases in in 124I-NaI PET/CT were further divided according to the presence or absence of FDG-uptake in 18F-FDG PET/CT. Survival analyses were performed using Kaplan-Meier curves and Cox proportional hazards model for uni- and multivariate analyses to assess the influence of prognostic factors on progression free survival (PFS).

Results Incomplete metastatic lymph node resection captured by 124I-NaI PET/CT (n=33) was an independent risk factor for recurrence (61% vs 25%, p =0.006) and shorter PFS (46 mo vs not reached, HR 4.0 (95%-CI, 1.7-9.2), p=0.001). Ultrasound could detect Lymph node metastases only in 19 patients (58%). Among patients with positive nodal status, FDG-avidity of metastatic lymph nodes worsened the outcome (16 vs 69, p=0.047). From all other investigated factors including age, N-stage (N1a vs N1b), and T-Stage (T4 vs T1-3) only large tumor size (pT4) had a significant impact on PFS (HR 2.9 (95%-CI, 1.3-6.4), p=0.007).

Conclusions Incomplete surgical clearance of lymph node metastases may increase the chances of recurrence and is an independent risk factor for impaired survival of patients with PTC. Pre-ablative (dual tracer PET/CT imaging) with 124I-Na and 18F- provides a powerful prognostic tool for these patients and may considerably complement the current risk stratification systems.