LAUSR

Dear Sir, We read with great interest the article titled “Differentiated thyroid cancer patients potentially benefiting from postoperative I-131 therapy: a review of the literature of the past decade” by Frederik A. Verburg et al. (EJNMMI, 2020, 47(1):78–83.) [1], who reported the results of an updated structured review of the literature pertaining to the clinical benefits of postoperative RAI in DTC in terms of recurrence-free and disease-specific survival. The authors concluded the prescription of adjuvant RAI treatment to all DTC patients with a primary tumor diameter exceeding 1 cm is a reasonable option. Yet wemight question the rationality of this conclusion in clinical application. Firstly, the article quoted four references to exemplify the validity of RAI treatment in non-microcarcinoma. Particularly, Reference 11 [2] by Carhill was quoted to illustrate RAI was a “favorable” prognostic factor regarding recurrence-free survival in stage I patients. Yet in Carhill’s original paper, RAI treatment appeared to be associated with “worse” disease-free survival (DFS) in stage I patients (RR 1.79, 95% CI, 1.14–2.86, p = 0.01). The worse DFS seen in stage I patients treated with RAI appears to be a function of the underlying criteria used by treating physicians to select patients for RAI. Actually, stage I covers a wide range of patient cohorts, including patients who are < 45 years. but with very poor non-metastatic clinical characters (by NTCTCS stage system). Apparently RAI treatment is more likely to be recommended to the aforementioned stage I subcohort with more unfavorable risk profile. Secondly, we failed to draw conclusion from this article that 1 cm is cut-off value for RAI indication. Although both Reference 13 [3] and Reference 18 [4] found a beneficial effect of RAI in certain cohort, the conclusions were based on multivariate analysis and we do not know the very role of primary tumor diameter. It is not evidence-based to jump to the cutpoint diameter 1 cm. In latest 2019 NCCN guideline for DTC, RAI is selectively recommended when primary tumor is 2–4 cm and typically recommended when primary tumor is larger than 4 cm [5]. Primary tumor diameter is one of the factors in RAI decision-making. But other clinicalpathological factors should also be taken into account to tailor treatment. Prospective data suggest that overall disease-specific and disease-free survival are not improved by RAI treatment in stage I and II patients, including patients with a primary tumor < 4 cm in diameter in absence of other adverse factors [6, 7], while patients with any size combined macroscopic invasion can benefit from RAI treatment, both in disease-free survival and disease specific survival [6]. To sum up, we hold the position that diameter is one of the crucial factors to tailor RAI strategy. But we are hesitant to draw the conclusion RAI treatment is appropriate for all DTC patients with a primary tumor diameter exceeding 1 cm without considering other risk factors.