The Treatment of High-Risk Thyroid Cancer
The Treatment of High-Risk Thyroid Cancer
ABSTRACT & COMMENTARY
Synopsis: Although the majority of thyroid cancers are well controlled with primarily surgical intervention, a substantial fraction recur and a number of patients die each year with recurrent and progressive disease. The National Thyroid Cancer Treatment Cooperative Study Registry has gathered data from 14 clinical centers that treat this disorder.
Source: Taylor T, et al. Ann Intern Med 1998;129: 622-627.
The treatment of high-risk thyroid carcinoma remains controversial. Key questions include the recommended extent of initial surgery, the role of iodine-131 therapy, and whether to include external beam irradiation in the initial treatment plan. In this report, data from 14 institutions in the United States and Canada (participating centers in the National Thyroid Cancer treatment Cooperative Study Register) were analyzed. Three hundred eighty-five patients with high-risk thyroid cancer (303 with papillary carcinoma and 82 with follicular carcinoma) were followed prospectively for a mean of three-and-a-half years for clinical outcomes of death, disease progression, and disease-free survival. Variables of interest included type and extent of surgery, iodine-131 therapy, and the use of external beam irradiation.
Characteristics that rendered an individual with thyroid cancer high-risk were aged older than 45 years, tumor more than 4 cm (for papillary) or more than 1 cm (for follicular), gross extraglandular invasion, neck node metastases, or distant metastases. Patients with follicular carcinoma were also considered high risk if the tumor was multifocal or if the histology revealed poor differentiation.
A total of 1607 patients with thyroid cancer were evaluated at the participating centers and, of these, 303 with papillary carcinoma and 82 with follicular carcinoma were considered high risk. Clinical outcomes were assessed with respect to each of the clinical variables mentioned.
Surgery. Of the 300 patients with papillary carcinoma, 85% had a total or near-total thyroidectomy as initial surgery. Only 3% had sub-total thyroidectomy, 9% had lobectomy, and 5% had lumpectomy or biopsy only. Similarly, for follicular carcinoma, 71% (of a total of 80 patients) had total or near-total thyroidectomy with the remainder having less extensive surgery. The overall complication rate for surgery was approximately 14%, with the most common complications being hypothyroidism or vocal cord palsy (or both hypothyroidism and vocal cord palsy). For those with papillary carcinoma, overall mortality was less with the more aggressive surgery, but the disease-free survival was not affected. The extent of surgery did not influence survival for those with high-risk follicular carcinoma.
Radioiodine Therapy. Radioiodine (iodine-131) was given to 85% of those with high-risk papillary carcinoma, but this only slightly improved cancer-specific survival in this group (compared to those that did not receive treatment) and it did not seem to influence disease-free survival at all. In contrast, radioiodine therapy was highly effective in improving outcome in patients with follicular thyroid carcinoma. Overall survival and cancer-specific survival was significantly greater for the 79% of these patients so treated, compared to the other high-risk patients not treated with radioiodine.
External Beam Radiation. Forty-six of 248 patients (18%) with high-risk papillary or follicular thyroid carcinoma had external beam radiation to the thyroid bed. The mean dose of radiation was 46 Gy over an average of 18.5 fractions. The most common clinical feature of those receiving external beam radiation was the presence of gross residual disease after surgery and/or extrathyroid invasion, although there were a substantial number of similarly involved patients not treated with this modality. Patients with high-risk papillary carcinoma treated with external beam radiation fared less well with regard to overall mortality than those not treated. Similarly, overall and cancer-specific mortality were worse for follicular carcinoma patients treated with external beam radiation.
Thus, this study supports a role for post-operative iodine-131 therapy for patients with high-risk follicular carcinoma and to a lesser extent, papillary thyroid carcinoma, but the study raises significant concerns about the use of external beam therapy in the same group.
COMMENTARY
The value of this report is that it has a relatively large series of patients for whom systematic evaluation was prospectively addressed. However, because treatment choices were not controlled and certainly varied among the various institutions, it is difficult to be confident in any, but the most basic conclusions. Certainly, the data support the use of radioiodine in high-risk patients.
The concerns about external beam irradiation must be taken with some skepticism. Patients in this series with the most negative prognostic factors (locally invasive tumors with gross residual disease) were compared to patients less likely to have these features. Taylor and colleagues seemed to conclude that external beam radiation therapy was harmful. However, external beam radiation therapy was only considered in a subset of patients with poor prognostic features. Another interpretation of the same data is that external beam irradiation did not reverse these negative prognostic features. It seems unlikely that the treatment actually accelerated tumor growth.
Thyroid cancer is relatively uncommon and the National Thyroid Cancer Treatment Cooperative Study Register is in the unique position to promote innovative interventional studies. It is hoped that with the data base currently generated and reported, future efforts will include prospective, well-controlled, interventional clinical trials.
Subscribe Now for Access
You have reached your article limit for the month. We hope you found our articles both enjoyable and insightful. For information on new subscriptions, product trials, alternative billing arrangements or group and site discounts please call 800-688-2421. We look forward to having you as a long-term member of the Relias Media community.