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Aggressive hormone suppression unnecessary in most thyroid cancers
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Extreme thyroid hormone suppression offered no additional survival benefit for patients with high-risk thyroid cancer, whereas moderate thyroid hormone suppression therapy can benefit most patients, according to research in The Journal of Clinical Endocrinology & Metabolism.
“Modest [thyroid-stimulating hormone] suppression may be the overall best target for many patients with thyroid cancer, and long-term complete TSH suppression may not be needed, even in patients with more high-risk thyroid cancer,” Bryan Haugen, MD, an investigator at the University of Colorado Cancer Center and head of the division of endocrine, metabolism and diabetes at the University of Colorado School of Medicine, told Endocrine Today. “Multicenter, controlled studies are needed to definitively answer this question.”
Bryan R. Haugen
Haugen, Aubrey A. Carhill, MD, of the department of endocrine neoplasia and hormonal disorders at The University of Texas MD Anderson Cancer Center, and colleagues analyzed data from 4,941 patients with a diagnosis of thyroid cancer (88% with papillary thyroid cancer; 8% with follicular thyroid cancer; 4% with Hurthle cell variant) enrolled in the National Thyroid Cancer Treatment Cooperative Study (NTCTCS) registry between 1987 and 2012. Researchers followed participants for an average of 6 years. Within the cohort, 3,268 participants received thyroid hormone suppression therapy, including those with TSH values recorded at least 50% or more of their follow-up time.
Researchers examined the effect of continuing thyroid hormone suppression therapy beyond 1, 3, and 5 years of follow-up by calculating mean TSH scores during the course of each patient’s remaining follow-up.
Researchers found that aggressive thyroid hormone suppression therapy resulted in no additional overall survival advantage when compared with moderate suppression therapy. The overall survival risk ratios for moderate therapy were 0.13, 0.09, 0.13 and 0.33 for thyroid cancer stages I through IV, whereas risk ratios for disease-free survival with moderate therapy were 0.52, 0.4 and 0.18 for stages I through III.
“Previous analysis noted only [overall survival] benefit with moderate [thyroid hormone suppression therapy], whereas current analysis also demonstrates a [disease-free survival] advantage,” the researchers wrote. “In contrast with our previous report, aggressive suppression conferred no additional survival advantage in the high-risk stages as compared with moderate [thyroid hormone suppression therapy]. Even limiting the analysis to patients with distant metastatic disease, maintaining mean TSH levels in the moderate range rather than aggressive is still associated with the best outcomes.”
Researchers also found improved overall survival in patients with stage III thyroid cancer who received postoperative radioiodine (RR = 0.66; P = .04), and in stage IV patients who received a total (RR = 0.66) or near-total thyroidectomy along with radioiodine (RR = 0.7; combined P = .049).
“In my mind, this study might give doctors pause when prescribing long-term, extreme TSH suppression in thyroid cancer patients,” Haugen said in a press release. “Contrary to our results, there is evidence from previous studies that extreme suppression may help in high-risk patients, but maybe then after a few years, when there is no evidence of disease recurrence, this study suggests that doctors could back off when we wouldn’t have before.” – by Regina Schaffer
For more information:
Bryan Haugen , MD, can be reached at 1635 Aurora Court, # 5, Aurora, CO 80045; email: bryan.haugen@ucdenver.edu.
Disclosure: Haugen reports receiving research funding from Veracyte and Genzyme and a one-time honorarium. Please see the full study for the other authors’ relevant financial disclosures.
Perspective
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Ronald N. Cohen , MD
Carhill and colleagues studied a large cohort of patients with differentiated thyroid cancer (DTC). Their full panel includes 4,941 patients diagnosed between 1987 and 2012, and total follow-up includes 34,631 patient-years. The study confirms previous findings that more complete surgery (total or near-total thyroidectomy) and radioactive iodine are beneficial in high-risk DTC patients. However, their most interesting findings relate to the effects of TSH suppression. Historically, TSH suppression has been used to decrease DTC recurrence and spread, with patients with more advanced DTC often being subjected to complete TSH suppression. The current study validates some aspects of TSH suppression, but challenges others. The investigators divide their “thyroid hormone suppression therapy” (THST) cohort into three groups: (1) aggressive THST (undetectable to subnormal TSH levels); (2) moderate THST (subnormal to normal TSH values); and non-suppressed THST (normal to elevated TSH levels). The researchers found that TSH suppression is associated with improved survival in all DTC stages, but, importantly, that aggressive THST does not impart a survival benefit over moderate THST, even for patients with metastatic disease.
This work is important because, although THST has been used for many years for patients with DTC, the degree of optimal TSH suppression is not known. Carhill and colleagues provide important data using a large cohort of DTC patients to suggest that moderate TSH suppression is useful, but that aggressive TSH suppression may provide no added benefit for many patients. Since aggressive THST may cause harm, this and other studies may change our TSH targets in the treatment of patients with DTC. It will be important for future studies to further define which DTC patients benefit from different degrees of TSH suppression so that care can be individualized and optimized.
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