Mortality rates from
thyroid cancer have fallen significantly in recent decades, almost certainly as the result of earlier diagnosis and improved treatment of differentiated (papillary and
follicular) thyroid cancer. Enhanced survival is likely a result of early diagnosis and
therapy applied at a disease stage when treatment is most effective. In the United States and Europe, most patients at high risk for relapse and death from
thyroid cancer are treated with total or near-total
thyroidectomy and receive radioiodine ablation of residual normal or malignant thyroid tissue, followed by treatment with
thyroid hormone, a strategy that cures more than 80% of patients. Still, some die of the disease and nearly 15% have local recurrences, while another 5% to 10% develop distant
metastases. Over 50% of recurrences appear in the first five years, but distant
metastases may surface years, and sometimes decades, after initial
therapy. Much has been learned about risk stratification to predict recurrence and death from
thyroid cancer but individual patients continue to have adverse outcomes not always foreseen by a low
tumor stage. Follow-up must accordingly be meticulous and prolonged. The National
Cancer Center Network (NCCN) has recently established consensus practice guidelines that give explicit advice about the diagnosis and management of benign and malignant thyroid
tumors, including paradigms for long-term follow-up and the treatment of recurrent disease. The guidelines confirm that diagnostic scanning with 131I and measurement of serum
thyroglobulin (Tg) levels are the mainstay of follow-up, offering the opportunity to detect recurrent or persistent
cancer at very early stages. These guidelines advocate TSH-stimulated serum Tg measurements, done either during
thyroid hormone withdrawal or stimulation with
recombinant human TSH (
rhTSH,
Thyrogen), that often identify the presence of
cancer well before diagnostic whole-body scanning or other imaging studies can spot the
tumor, which offers the opportunity to treat recurrent disease at an early stage. The use of
rhTSH adds a new dimension to long-term follow-up that avoids putting patients through the symptoms of
hypothyroidism, and offers the opportunity to follow some patients with
rhTSH-stimulated serum Tg levels without performing 131I whole-body scans. A multicenter international study has shown that serum Tg measurements alone are not as sensitive in the identification of patients with persistent or recurrent
tumor as are
rhTSH-stimulated serum Tg determinations. Although not yet approved for preparation of patients for 131I
therapy,
rhTSH has been used successfully in a compassionate use program for this purpose in a relatively large number of patients. Formal clinical investigations now planned to provide guidelines for the use of
rhTSH for therapeutic 131I portend a new set of effective therapeutic paradigms for the management of differentiated
thyroid cancer.