An Updated Systematic Review and Commentary Examining the Effectiveness of Radioactive Iodine Remnant Ablation in Well-Differentiated Thyroid Cancer

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Radioactive iodine remnant ablation (RRA) is used to destroy residual normal thyroid tissue after complete gross surgical resection of papillary or follicular thyroid cancer. The article updates a prior systematic review of the literature to determine whether RRA decreases the risk of thyroid cancer-related death or recurrence at 10 years after initial surgery, including data from 28 studies. No long-term randomized trials were identified, so the review is limited to observational studies. The incremental benefit of RRA in low risk patients with well-differentiated thyroid cancer after total or near-total thyroidectomy who are receiving thyroid hormone suppressive therapy remains unclear.

Section snippets

Selection of relevant studies for the systematic review

The inclusion and exclusion criteria for studies in the review have been previously described [11]. Studies were eligible for inclusion if they were randomized, controlled trials or cohort studies of adult patients that had:

  • Well differentiated thyroid cancer (defined as either papillary, follicular or follicular variant of papillary);

  • Surgical treatment involving bilateral resection, such as total, near-total, or subtotal thyroidectomy (ie, surgery that was more extensive than ipsilateral

Search strategy for the updated systematic review

One investigator performed an updated search of seven different electronic databases for the time period spanning from the prior review (original search in late 2002) until August 2007. The databases searched included: Medline and other nonindexed citations, the Cochrane Database for Systematic Reviews, Database of Abstracts and Reviews, the Controlled Clinical Trials Database, American College of Physicians Journal Club, the Cochrane Clinical Trials Registry, and Embase. The search was

Data abstraction

One investigator abstracted the data. If detailed information on completeness of resection of gross disease in the primary surgery was not reported, data from “low-risk” postsurgical stage subgroups were abstracted (as defined by the individual author or reported standard staging systems). The definitions of “low risk” staging (if not provided by individual authors within the included articles) were defined as in the original review [11]. If “completely resected” or “low risk” were not

Statistics

Data adjusted for prognostic factors or cointerventions were tabulated as reported in the primary studies without pooling because of important clinical and methodologic heterogeneity among studies. The criterion for statistical significance was set at alpha = 0.05, with the exception of heterogeneity assessments, for which alpha = 0.10. The authors pooled unadjusted data for the 10-year outcomes of thyroid cancer-specific mortality, any recurrence, local recurrence (in the neck or upper

Results

In this updated systematic review, two reviewers independently reviewed 863 unique abstracts and citations and 74 potentially relevant full-text published articles. The authors included data from 28 studies, seven studies published since the time of the original review [12], [13], [14], [15], [16], [17], [18] (Fig. 1). The authors had planned to include data from all nonoverlapping studies from the original review [13], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31]

Summary of analyses statistically adjusted for prognostic factors or cointerventions

Because thyroid cancer-related outcomes are dependent upon important prognostic variables, the authors examined the results of studies in which the treatment effect of RRA was examined after statistical adjustment for such factors (or intended adjustment in the case of conditional analyses) (Table 1, Table 2, Table 3, Table 4). Some form of statistical adjustment of important prognostic factors was considered a methodologic quality indicator. The authors observed that in 12 prognostically

Unadjusted pooled analyses

No newer nonoverlapping unadjusted thyroid cancer-related mortality data was found in the authors' updated review, so the original pooled analysis [11] was not redone. The authors originally reported [11] that there was significant statistical heterogeneity of treatment effect among 16 analyses examining the effect of RRA on 10-year thyroid cancer-related mortality in a total of 6,464 patients (chi-square 27.44, 15 degrees of freedom, P = .025) [19], [20], [21], [24], [26], [29], [30], [31],

Commentary

Upon carefully examining the best existing long-term observational evidence, the authors could not confirm a significant, consistent, benefit of RRA in decreasing cause specific mortality or recurrence in early stage WDTC. RRA use was associated with a significantly decreased risk of distant metastases; however, this event was relatively rare in papillary cancer. The relatively low risk of thyroid cancer-related death in early stage thyroid carcinoma patients may limit the ability to prove a

Acknowledgments

The authors would like to thank the following investigators for providing us with information related to their studies: Adil Al-Nahhas (Padova University, Italy), David Brams (Lahey Clinic, United States), Steve Hyer (Royal Marsden Hospital, United Kingdom), and Tony Panzarella (Princess Margaret Hospital, Canada).

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      However, because the MACIS scheme was designed to predict CSM, the presence or absence at initial presentation of RNM, which was not found to be an independent variable for CSM by our multivariate analyses,15 is not taken into consideration within the MACIS prognostic score. Like most previously reported studies36,37 regarding the impact of RRA on outcome in APTC, this study is not randomized,34,38-40 and it is from 1 institution and retrospective. However, our 2952 LRAPTC patients with a MACIS score of less than 6 were, during the years of our 6-decade study, managed by the same team of endocrinologists, surgeons, and nuclear medical specialists, and the patients who had BLR alone were compared with those having BLR+RRA within the same time frame.

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    Anna Sawka is a New Investigator supported by the Canadian Institutes of Health Research (CNI-80701).

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