Value of Radioactive iodine therapy for low-risk differentiated thyroid cancer - where is the gap of evidence?

627 Purpose: Radioactive iodine (RAI) therapy has been performed for patients with differentiated thyroid cancer (DTC) following surgery. The new 8th edition of AJCC staging for DTC increased age cut-off from 45 to 55 years old and down-staged lymph node metastases (both central and lateral compartments) in older patients from Stage III or IV to Stage II, as the 10 year-disease-free survival (DFS) in this group is currently 85-95%. The size cutoff for Stage I disease also increased from 2 cm to 4 cm for older patients with 10-year DFS of 98-100% . Several published clinical guidelines revealed different recommendations for the low-risk DTC patients. The purposes of this study are to 1) review the various societal guidelines and recommendation of RAI, 2) to evaluate the trending of RAI therapy and patient risk stratification in our institution. Methods: Major clinical guidelines for diagnosis and management of thyroid cancer were reviewed in regards to the indications for RAI therapy for DTC. These include the following guidelines: SNMMI (Society of Nuclear Medicine and Molecular Imaging), ATA (American Thyroid Association), and NCCN (National Comprehensive Cancer Network). In addition, the total number of RAI therapies performed from 2012 to 2018 were extracted from the Radiology Information System. The presence or absence of various risk factors were recorded, including presence of extrathyroidal extension (ETE), distant and lymph node metastases, aggressive histology (angiolymphatic invasion, perineural invasion), positive or close margin (< 1mm), incomplete resection, primary tumor larger than 4 cm, high postoperative thyroglobulin (Tg), gross remnant tumor, and other pertinent clinical history. The ATA risk stratifications were recorded for 76 patients who underwent RAI from 1/1/2017 to 12/31/2018. Results: The 2015 ATA risk stratification system and recommendation of RAI by three societal guidelines are summarized in Table 1. The major discrepancy is RAI indication for low-risk DTC larger than 1 cm without aggressive histology, ETE, metastasis, vascular invasion, and LN metastases < 2mm, where SNMMI guidelines recommend RAI though ATA and NCCN guidelines do not. The total number of RAI treatments for DTC at our institution has declined 62%, from 88 cases in 2012 to 33 cases in 2018. Among 79 total patients, 46 treated in 2017 and 33 in 2018, no detailed medical records were available in 8 patients referred from outside hospitals. Out of 71 patients, presence of LN metastases was seen in 40 (59.2%), distant metastases in 22 (31%), ETE in 20 (19.7%), positive or close margin in 12 (13.3%), larger than 4 cm in 12 (13.3%), and angiolymphatic invasion in 8 (5.3%). Base on the ATA risk stratifications, 51 patients (72%)were high-risk, 20 patients (28%) were intermediate-risk. No low-risk patients were referred to RAI therapy in the last two years. Conclusions: Our preliminary analysis showed the recent RAI referrals are limited to high-risk and intermediate-risk DTC patients, presumably reflecting the ATA and NCCN guidelines. Given the excellent disease-free survival of low-risk DTC, benefits of reduction of recurrence have to be balanced against potential side effects of RAI. Different recommendations of clinical guidelines by the various academic organizations can lead to confusion among patients who seek medical care. The current gap of evidence includes the cutoff values of post-thyroidectomy nonstimulated Tg to further refine “very low-risk category” patients who may safely avoid RAI, and the use of molecular markers to improve the current risk stratification. Patients reported outcome is another area of further investigation in order to facilitate shared-decision making.