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Can the course of low-risk thyroid cancer be accurately predicted?

Scoring can predict the course of low-risk disease.

Papillary thyroid cancers represent around 80% of all thyroid cancers seen in doctors' offices, and most present when they are small (a median 1.7 cm in diameter) and unlikely to have gross extrathyroid invasion (less than 15%).

While 40% of patients will have positive regional lymph nodes, only 2% will have distant metastasis.

This is in contrast to follicular thyroid cancer, the next most common type, which is found in older patients who often have larger tumors (average of 3.5 cm), and that has a 25-year mortality rate that is six times higher.

At the Mayo Clinic, we have used our database of 2,512 papillary thyroid cancer patients treated since 1940 to evaluate the different thyroid cancer scoring schemes, and found that they all perform fairly similarly and do fairly well at predicting prognosis.

We have since 1994 used the MACIS [metastasis, age, completeness, invasive, size] score we developed, where a score of 6 is the cutoff between high and low risk. We have reported that 84% of the 2,512 patients were low risk according to the MACIS score, and their mortality rate at 20 years was less than 1%. In contrast, those patients with a score higher than 6 had a 32% mortality rate.

So I think we can predict who can be treated conservatively with surgery and thyroid hormone suppression, and who needs more advanced treatment.

Most papillary thyroid cancers are bilateral and many have positive regional nodes. Therefore, at Mayo, normal treatment is bilateral lobar resection with evaluation of the nodes. We have reported that compared with lobectomy, this procedure decreases the recurrence rate in low-risk patients from 25% to 5%, though the mortality rate stays the same. In high-risk patients, this procedure reduces recurrence by two-thirds and reduces mortality by half.

We do not believe in using indiscriminate radioiodine remnant ablation. In 1,163 of our low-risk patients, of whom 43% had remnant ablation, we found a mortality rate of 0.6% at 20 years out with ablation, and a rate of 0.4% without ablation. And we still found no difference in recurrence or mortality when we stratified the patients according to their nodal status.

At Mayo, we ablate only patients with a MACIS score of 6 or above, and those with follicular cell derived cancers. Low-risk patients we follow with ultrasound surveillance, and when we find a nodal metastasis we use ultrasound-guided alcohol injection to ablate that specific node.

We are concerned about the widespread use of radioiodine ablation when it is not necessary, and we don't think it should be used for low-risk patients.

DR. HAY is a professor of medicine in the division of endocrinology, diabetes, metabolism, and nutrition at the Mayo Clinic, Rochester, Minn.


The course of low-risk disease is hard to predict.

According to a review of almost 54,000 cases of thyroid cancer treated between 1985 and 1995, the 10-year survival rate for cases of papillary thyroid cancer is 93%. However, because papillary thyroid cancer makes up such a preponderance of thyroid cancer cases, that 7% mortality rate made up 53% of all the thyroid cancer deaths.

The 7% mortality rate reported in that review represents the experience across the nation. It is more than twice the 2% rate described by the Mayo Clinic investigators, and therein lies part of the rub. There are institutional differences, probably for many reasons, and the experience of one place may not be reflectively translatable to all institutions.

Since 1973, there has been a 2.4-fold increase in thyroid cancer, and almost all of that increase has been in small papillary cancers. For women, the mortality rate has been falling significantly over this period. But for men, it has been increasing by 2% per year between 1992 and 2000.

The 7% mortality rate, and the fact that mortality is increasing in men, suggests that low-risk is not zero risk. And we cannot reliably predict who is low risk.

Most important, no staging scheme has been able to show that it accurately predicts low-risk cancers or survival.

Investigators such as Dr. James Brierley of the University of Toronto have taken the various staging schemes, including the AMES [age, metastasis, extent, and size] classification system, the AGES [age, grade, extent, and size] system, and the MACIS system, and tried to determine how prognostic they are. Dr. Brierley found that for any of the six schemes he examined, about 80% of deaths are not predicted by staging. Others have found the staging systems even less predictive of prognosis.

The staging systems are imperfect at least in part because thyroid cancer is unpredictable. In a Mayo Clinic study from Dr. Hay, of 535 patients with thyroid papillary microcar-cinoma, the median tumor size was only 8 mm in diameter. But 32% of the patients had nodal metastasis, 20% had multifocal disease, and two patients even died from their thyroid cancer. Among those with positive lymph nodes, the recurrence rate at 30 years was 18%.

There may be low-risk thyroid cancers, but low-risk is not synonymous with no risk. Therefore, I think the only papillary thyroid cancers that might require less therapy are those in patients with no family history, no other thyroid cancer related diseases, and no history of radiation treatment. In addition, the patient should be younger than 45 years old, have only one primary tumor less than 1 cm with classic histology, and have no invasion or metastasis beyond the thyroid capsule.

DR. MAZZAFERRI is a professor of medicine at the University of Florida, Gainesville, and professor emeritus of internal medicine and endocrinology at Ohio State University, Columbus.

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Author:Hay, Ian D.; Mazzaferri, Ernest L.
Publication:Internal Medicine News
Geographic Code:1USA
Date:Oct 1, 2007
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