CORONADO, CALIF.– In an analysis of primary treatments for all stages of differentiated thyroid carcinoma, only thyroid hormone suppressive therapy was associated with both improved overall survival and disease-free survival.

Further, when examining the degree of thyroid hormone suppressive therapy (THST), aggressive THST conferred no additional survival benefit when compared with moderate THST, even when limiting the analysis to patients with distant metastatic disease, results from a long-term analysis of registry showed.

Those are key findings from an updated analysis of data from the National Thyroid Cancer Treatment Cooperative Study Group Registry, which were presented by lead study author Dr. Aubrey Carhill during the annual meeting of the American Thyroid Association.

“To date there are no prospective studies evaluating the longitudinal outcomes of initial long-term therapies in differentiated thyroid carcinoma,” said Dr. Carhill of MD Anderson Cancer Center, Houston. “In the absence of prospective trials, there has been significant reliance on retrospective studies with limited numbers of patients and low event rates as well as significant reliance on expert opinion to guide clinical practice.”

For example, current ATA guidelines for TSH suppression suggest that in long-term follow-up of patients with differentiated thyroid cancer, “those with persistent disease should have TSH levels suppressed to undetectable levels and maintained indefinitely,” Dr. Carhill said, while disease-free, higher-risk patients “should be suppressed to low-moderate levels continued between 5 and 10 years and low-risk patients should be maintained in the low-normal range. Similar levels of evidence exist to support the use of radioactive iodine and the degree of surgical extent.”

The challenge for clinicians, she continued, becomes balancing the potential risks of more aggressive therapies, such as aggressive thyroid hormone suppression, and the risks associated with long-term thyrotoxicosis with the potential benefits of treatment. “This is not always clear, especially in patients who are at very low risk for cancer-specific mortality,” she said. “There remains a need for accurate prognostication in order to identify which patients will benefit from different treatment modalities because current staging systems have limited ability to predict response to treatment.”

Formed in 1987, the National Thyroid Treatment Cooperative Study Group is a multi-institutional effort to assess long-term management of outcomes on patients with differentiated thyroid cancer. The purpose of the present study was to provide a more current analysis of the prospectively collected data, which was last analyzed in 2001. All staging is tracked according to the registry’s staging system, which is very similar to that of the American Joint Committee on Cancer’s TNM Staging System. Therapies analyzed included total/near total thyroidectomy (T/NTT) vs. a lesser extent of surgery; radioactive iodine (RAI) vs. no RAI; and increasing degrees of THST over time.

Dr. Carhill presented findings from an analysis of the effects of initial therapies in 4,941 patients treated at 11 centers in North America between 1987 and 2012. The median length of follow-up was 6 years, which translated to 34,631 person-years of documented follow-up time. The researchers used univariate and multivariate analyses to assess overall and disease-free survival. Moderate THST was defined as TSH maintained in subnormal or normal levels, while aggressive THST was defined as that maintained in undetectable or subnormal levels.

Improved overall survival was observed in stage III patients who received RAI (risk ratio, 0.66; P = .04) and in stage IV patients who received T/NTT and RAI (RR, 0.66 and 0.70, respectively; combined P = .049). Moderate but not aggressive THST was associated with significantly improved overall survival in all stages (RR, 0.13 in stage I, 0.09 in stage II, 0.13 in stage III, and 0.33 in stage IV), as well as with improved disease-free survival (RR, 0.52 in stage I, 0.40 in stage II, 0.18 in stage III, and no RR in stage IV).

In stage I patients, RAI conferred worse disease-free survival (RR, 1.79; P = .0005). “However, further propensity analysis demonstrated that there was no difference in disease-free survival when patients were stratified according to their propensity to receive radioactive iodine,” Dr. Carhill said.

To evaluate the optimal duration of THST, the researchers examined the effect of continuing degrees of suppression beyond 1, 3, and 5 years of follow-up. After 1 and 3 years of follow-up, both initial stage and moderate TSH suppression were independently predictive of improved overall survival (RR, 0.31 and 0.29, respectively). However, after 5 years of follow-up, “although initial stage remained independently predictive, there was no further benefit with any subsequent degree of TSH suppression,” Dr. Carhill said.

The study “confirms prior registry findings of a survival benefit in high-risk groups treated with T/NTT and RAI, and there is no disease-free survival benefit in low-risk groups receiving postoperative RAI,” she concluded. “We also report for the first time that in multivariate analysis of primary treatments for DTC [differentiated thyroid cancer], in all stages, only THST was associated with both improved overall survival and disease-free survival. When examining the degree of THST, aggressive THST confers no additional survival advantage as compared with moderate THST, even in patients with distant metastatic disease, which remains particularly relevant given the risks associated with long-term thyrotoxicosis.” She acknowledged certain limitations of the study, including the potential for institutional bias. “However, we feel that this is somewhat offset due to the size of the registry cohort and the number of sites involved” Dr. Carhill said.

The registry has received support from Genzyme and Pfizer. Dr. Carhill reported having no financial disclosures.

dbrunk@frontlinemedcom.com

On Twitter @dougbrunk

Moderate THST linked to improved survival in thyroid cancer