Iodine Radioisotope Diagnostic Scanning With SPECT/CT After Thyroidectomy for Thyroid Cancer: Essential Data or Unnecessary Investigation?

In the clinical management of patients with differentiated thyroid cancer after total thyroidectomy, there is controversy on the utility of postsurgical iodine radioisotope diagnostic imaging (using 131-I or 123-I), with or without single photon emission computed tomography (SPECT)/computed tomography (CT). Some arguments supporting the use of postsurgical radioactive iodine (RAI) diagnostic scans, with or without SPECT/CT, include beliefs that this procedure may optimize postoperative risk classification by ascertaining disease status/staging, optimize selection of patients with RAI-avid disease for RAI therapy, optimize RAI therapeutic dose activity selection, and identify patients who may benefit from additional surgical therapy (such as debulking of distant metastases or resection of a large thyroid remnant) (1). Theoretical challenges in endorsing routine use of postoperative RAI diagnostic scans, with or without SPECT, may include the lack of controlled trials proving that a strategy of using such scans to guide RAI treatment decisions (including patient selection for treatment or dose activity selection) improves long-term patient outcomes or reduces overall healthcare costs, compared to a strategy of therapeutic decision-making based on clinicopathological stage with additional cross-sectional imaging (such as pre- or postoperative neck ultrasound). Moreover, there are conflicting data on whether pretherapy 131-I diagnostic scans reduce efficacy of remnant ablation, with some authors reporting an adverse impact (2, 3) and others reporting no significant difference, as compared to empiric 131-I treatment (4). A pretherapy 131-I scan dose activity of 1 mCi (37 MBq) has been reported to be less likely to impair success of remnant ablation, compared to higher dose activities (5). A practical issue in considering the feasibility of postsurgical RAI diagnostic scanning in medical decision-making is the institutional ability/inability to modify preordered therapeutic dose activities of 131-I, in response to data obtained in the days preceding therapy. Clinical practice guideline recommendations on the use of postsurgical RAI diagnostic scanning are variable. The American Thyroid Association has recommended select use of postsurgical RAI diagnostic scanning or uptake measurement if the size of the thyroid remnant cannot be determined by other means or if the results would impact decision-making (on selection for RAI treatment or dose activity selection) (6). A European consensus panel provided a conditional recommendation for the use of postsurgical RAI diagnostic scanning if there is uncertainty about the extent of thyroidectomy (7). The British Thyroid Association suggested that preablation scanning is not routinely indicated but can be performed to assess remnant size if the extent of thyroidectomy is uncertain (8). The Society for Nuclear Medicine has indicated that “routine” preablation scanning “can be useful in guiding 131-I therapy” (9). The European Association for Nuclear Medicine has recommended that 131-I diagnostic scanning or uptakes should be avoided in cases where RAI therapy is clearly necessary because the results would not alter clinical management and the procedure may impair therapeutic efficacy (10). The Latin American Thyroid Association has acknowledged the controversy surrounding this procedure (11). In summary, there is some disagreement internationally on the utility of post-thyroidectomy RAI diagnostic scans. In this issue of the JCEM, Avram et al (12) have reported the impact of preablation 131-I scanning with SPECT/CT on disease status classification using the American Joint Committee on Cancer TNM (7th ed.) system (13) in a prospective, single-institution observational study. The study population consisted of 320 consecutive patients, including adults and children, referred for consideration of postoperative 131-I treatment due to suspicion of “increase in tumor biologic aggressiveness,” based on histopathological risk factors. The authors describe this population as intermediate and high risk, based on histopathological data such as: 30% prevalence of vascular invasion, 36% prevalence of extrathyroidal extension, 26% prevalence of positive surgical margins, and 47% prevalence of resected cervical node metastases (12). In this study, patients underwent thyroid hormone withdrawal, were instructed to follow a low-iodine diet for 2 weeks, and received 1 mCi (37 MBq) of 131-I for diagnostic scanning with SPECT/CT imaging. All scans were read by two respective readers: one reader blinded to the clinical, pathological, and biochemical data; and one reader who was not blinded to such data. Consensus between readers was achieved on the final interpretation. In individuals aged < 45 years, 131-I diagnostic scans with SPECT/CT suggested the presence of distant metastases in 4% of patients and nodal metastases in 44% of patients, resulting in up-staging from TNM stage I to II in 4% of patients (compared to staging based on clinicopathological characteristics) (12). In individuals aged 45 years and older, 131-I scans with SPECT/CT suggested distant metastases in 10% of patients and nodal metastases in 28% of patients, resulting in up-staging using the TNM system in 25% of individuals (12). The percentage of individuals who were initially classified as clinical node negative (histopathological N0 or Nx) in whom iodine radioisotope scans with SPECT/CT suggested the presence of nodal metastases was 38% of individuals aged < 45 years and 24% of older individuals (12). There was 92% agreement between 131-I pre- and post-therapy planar imaging findings (12). The authors reported that additional foci were identified on post-therapy scans of 6% of patients, although this resulted in up-staging of TNM disease status in only 1.4% of cases (12). Some strengths of the study by Avram et al (12) include the inclusion of consecutive patients and the incorporation of blinded readers in the study design. Some study limitations include a lack of “gold standard” histopathological confirmation of suspected metastases, a lack of detailed information on how the data from postsurgical radioisotope scans and SPECT/CT impacted clinical management, and a lack of long-term follow-up data. Also, given the intermediate and high-risk nature of the population studied, the results are not directly applicable to low-risk, well-differentiated thyroid cancer patients. This study did not examine the impact of alternative techniques, such as the use of recombinant human TSH preparation for RAI diagnostic scanning, or the use of 123-I diagnostic scintigraphy. The findings reported by Avram et al (12) are complementary to several recent studies from other institutions. Van Nostrand et al (1) reported that of 355 pretherapy diagnostic radioisotope scans reviewed (including 337 I-123 scans and 18 131-I scans), a total of 53% of patients had findings that could potentially alter clinical management, including 14% with suggestion of lymph node metastases and 4% suggestive of distant metastases. Furthermore, Chen et al (14) reported that pretherapy 123-I scans provided additional “critical” information in 25% of cases. Moreover, this body of literature incites many related clinical questions, such as what constitutes the optimal therapeutic management relative to iodine radioisotope diagnostic scan (with or without SPECT/CT) findings (including selection for 131-I therapy and optimal therapeutic dose activity)? What is the optimal clinical management when the findings on postsurgical diagnostic radioisotope scanning conflict with other relevant data, such as stimulated thyroglobulin measurements or worrisome clinicopathological features? Is a strategy of selective or routine postsurgical iodine radioisotope diagnostic scanning more effective at improving long-term patient outcomes (including therapeutic efficacy and side effects) than a strategy of management based on clinicopathological features (with or without additional cross-sectional imaging)? Future prospective controlled trials are needed to answer such questions. In the meantime, from a medical decision-making perspective, the fundamental question as to whether postsurgical iodine radioisotope scanning constitutes essential data or unnecessary investigation is likely to be largely dependent on factors such as the individual patient situation, preferences, practice patterns, and feasibility considerations. A.M.S. is supported by the Cancer Care Ontario Research Chair Program in Health Services Research. Disclosure Summary: A.M.S. has nothing to disclose. computed tomography radioactive iodine single photon emission computed tomography.

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