CRD summary

This review concluded that there was no significant consistent benefit of radioactive iodine remnant ablation in decreasing cause-specific mortality or recurrence in early stage well-differentiated thyroid cancer. There was an association with significantly reduced risk of the relatively rare outcome of distant metastases. A lack of validity assessment and some other issues made the reliability of this conclusion unclear.

Authors' objectives

To assess the effect of radioactive iodine remnant ablation (RRA) for early stage well-differentiated thyroid cancer (WDTC) on the risk of thyroid cancer-related mortality and disease recurrence.

Searching

MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, DARE, Cochrane Central Register of Controlled Trials (CENTRAL) and ACP Journal Club were searched for studies reported in English from late 2002 to August 2007. Search terms were reported. All studies from the original review (see Other Publications of Related Interest) were included in the review.

Study selection

Randomised controlled trials (RCTs), controlled trials and cohort studies that enrolled adult patients with WDTC treated surgically with bilateral resection (total, near-total or subtotal thyroidectomy) and treated with radioactive iodine ablation within one year of surgery were eligible for inclusion in the review. Studies were required to have a mean or median follow-up of at least five years and to report 10-year data for one of the outcomes: cancer-related deaths; cancer recurrence; local-regional recurrence in the thyroid bed or regional lymph nodes; and distant metastases.

Where reported, included studies were mostly of patients with papillary, follicular or Hürthle cell carcinomas, or a mixture of these histological subtypes. The extent of surgery varied considerably between studies.

Two reviewers independently assessed the studies for inclusion; disagreements were resolved through consensus.

Assessment of study quality

Studies were not assessed for validity, although they were categorised by whether analyses had been adjusted for important prognostic factors.

Data extraction

Data to enable calculation of risk differences (RD) with 95% confidence intervals (CI) were extracted by one reviewer.

Methods of synthesis

Unadjusted 10-year outcome data were pooled using random-effects model meta-analyses to calculate summary risk differences with 95% CI. Statistical heterogeneity between studies was assessed using Χ² and I² statistics. Where heterogeneity was statistically significant, pooled outcomes were not reported. Data adjusted for prognostic factors or concomitant interventions were not combined statistically due to clinical and methodological heterogeneity between studies.

Results of the review

Twenty-seven studies were included in the review, 20 of which were included in the previous systematic review. All studies were cohort studies. Where reported, median follow-up ranged from five to 21.4 years. Seventeen studies reported the treatment effect of RAA after statistical adjustment for prognostic factors. RAA was associated with a significant reduction in the risk of thyroid cancer related mortality.

There were no additional unadjusted data on thyroid cancer mortality data; therefore, the authors reported the results of the analysis conducted in their previous review (see Other Publications of Related Interest), namely that there was a high degree of statistical heterogeneity between the 16 included studies (n=6,464, Χ²=27.44, p=0.025). Ten-year incidence of thyroid cancer mortality in the five studies of papillary patients only was estimated to be 1.7% (n=2,627).

Unadjusted analyses for the outcome of any recurrence (present review): There was statistically significant heterogeneity (n=5,307, Χ²=122.71, p<0.00001, I²=91%) and loco-regional recurrence (n=1,244, Χ²=20.36, p=0.001, I²=75%). RRA was associated with a statistically significantly reduced risk of distant metastasis (RD -2%, 95% CI -4% to -1%, I²=0%; n=2,263).

Authors' conclusions

There was no significant consistent benefit of RRA in decreasing cause-specific mortality or recurrence in early stage WDTC. There was an association with a significantly reduced risk of the relatively rare outcome of distant metastases.

CRD commentary

The review question and inclusion criteria were clear. The authors searched several relevant databases. The restriction to studies reported in English increased risks of relevant studies being missed and language bias being introduced into the review. The authors reported that they used methods designed to reduce reviewer bias and error in study selection, but not data extraction. The lack of a validity assessment made it difficult to determine the reliability of the evidence. Study details were not provided for all studies, which made it difficult to assess the appropriateness of pooling data and the reliability of pooled results. The analyses were reasonable. Heterogeneity was explored and taken into account in decisions on the wisdom of pooling data, but was nonetheless significant.

The authors' conclusions reflected the results of the review, but the lack of a validity assessment and other issues with the review process made their reliability unclear.

Implications of the review for practice and research

Practice: The authors stated that physicians who treated early stage WDTC should evaluate all data carefully in each case and advise patients of the uncertainty of the evidence for RRA and all acceptable treatment options and the implications of declining or accepting RRA.

Research: The authors stated that long-term higher quality evidence on use of RRA for treatment of WDTC was needed to inform future clinical practice.

Funding

Canadian Institutes of Health Research CNI-80701.

Bibliographic details

Sawka AM, Brierley JD, Tsang RW, Thabane L, Rotstein L, Gafni A, Straus S, Goldstein DP. An updated systematic review and commentary examining the effectiveness of radioactive iodine remnant ablation in well-differentiated thyroid cancer. Endocrinology and Metabolism Clinics of North America 2008; 37(2): 457-480. [PubMed: 18502337]

Original Paper URL

http://dx.doi.org/10.1016/j.ecl.2008.02.007

Other publications of related interest

Sawaka AM, Thephamongkhol K, Brouwers M et al. Clinical review 170: A systematic review and meta-analysis of the effectiveness of radioactive iodine remnant ablation for well-differentiated thyroid cancer. Journal of Clinical Endocrinology and Metabolism 2004; 89: 3668-3676.

Indexing Status

Subject indexing assigned by NLM

MeSH

Carcinoma, Papillary /pathology /radiotherapy /surgery; Carcinoma, Papillary, Follicular /pathology /radiotherapy /surgery; Disease Progression; Humans; Iodine Radioisotopes /therapeutic use; Neoplasm Recurrence, Local /prevention & control; Neoplasm, Residual; Radiotherapy, Adjuvant; Thyroid Neoplasms /pathology /radiotherapy /surgery; Thyroidectomy; Treatment Outcome

AccessionNumber

12008105200

Database entry date

09/02/2011

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.