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The incidence of well-differentiated thyroid cancer (WDTC) has been rising steadily in the United States over the past three decades, mainly due to improved detection of subclinical disease. A new study, however, also adds to the growing concern about the risk of secondary cancers in thyroid cancer patients treated with radioactive iodine (RAI).

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"Thyroid cancer is the most common endocrine cancer in the United States, and we are treating an increasing number of these cancers using both surgery and radioactive iodine," the study's lead researcher, Sudipto Mukherjee, MD, PhD, Associate Staff Member in the Department of Hematology and Medical Oncology at the Cleveland Clinic, said in a news release.


The study, presented at the American Society of Hematology Annual Meeting, found that thyroid cancer patients who undergo surgery and receive adjuvant RAI have an increased risk of myelodysplastic syndromes (MDS) (Abstract 612).


"Because we're detecting many of these cancers when they are small-less than 2 cm-and there is lack of data demonstrating better survival with radioactive iodine-we may be overtreating them. As a result, we could be exposing low-risk thyroid cancer patients to the risk of secondary cancers including hematologic malignancies years later."


MDS risk appears to be increased within the first two years of treatment with RAI.


The researchers-first author is Christopher Pleyer, MD-examined 18 Surveillance Epidemiology and End Results (SEER) registries to identify patients with WDTC treated with surgery, RAI, and external-beam radiation therapy who later developed MDS. A total of 132,157 WDTC cancer patients treated from 1973 to 2011 were identified. Of these, 53 percent were treated with surgery alone, while 45 percent underwent surgery plus adjuvant RAI. Two percent underwent external-beam radiotherapy and surgery with or without adjuvant RAI. Patients were followed for a median of five to six years after thyroid cancer treatment.


Fifty nine patients developed MDS. Of these, 24 had surgery alone, while 27 received surgery plus RAI; four patients had external-beam radiation. Compared with those treated with surgery alone, thyroid cancer patients who received RAI with or without the radiation therapy had an increased risk of developing MDS within the first two years of treatment, the researchers reported.


Beyond two years, however, the risk for MDS in those treated with RAI dropped to baseline rates that were comparable to those of the general population. Interestingly and of concern, Mukherjee said, a trend towards a rise in MDS incidence was observed starting at 12 years after treatment, among those who underwent RAI therapy, but this did not reach statistical significance.


Possible Reasons

The reason for the early increased rates of MDS in patients treated with RAI remains unclear, he said. "The results could be an ascertainment bias. The increased risk could be real, or it could be that increased rates of MDS in patients receiving radioactive iodine therapy is an effect of these patients being seen more frequently by oncologists and hence being diagnosed earlier than those undergoing surgery alone."


Still, he said, the results indicate that there is a risk of MDS with RAI therapy, and oncologists should exercise caution when treating low-risk WDTC tumors, especially when there are few data suggesting any efficacy of adjuvant RAI in preventing recurrences or prolonging survival in these patients.


"For some patients with small WDTC cancers without high-risk features, particularly those with extension beyond the thyroid gland or with lymph node involvement, the American Thyroid Association guidelines do not support routine use of radioactive iodine for these low-risk tumors. We don't want to overtreat these patients, so we should weigh the risks of treatment very carefully," he said.


In addition, as he and his colleagues concluded in the abstract: "Considering the long latency of MDS seen in atomic bomb cohorts with risk persisting beyond 40 years, there is a growing clinical concern that MDS rates are likely to rise in WDTC patients due to a combination of factors including the relative young age of WDTC patients at the time of diagnosis, a high proportion of long-term survivors, and the recent trend in overdiagnosing and subsequently overtreating WDTCs."