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Thyroid Cancer Treatment (PDQ®)

Recurrent Thyroid Cancer

Patients treated for differentiated thyroid cancer should be followed carefully with physical examinations, serum quantitative thyroglobulin levels, and radiologic studies based on individual risk for recurrent disease.[1] Approximately 10% to 30% of patients thought to be disease free after initial treatment will develop recurrence and/or metastases. Of these patients, approximately 80% develop recurrence with disease in the neck alone, and 20% develop recurrence with distant metastases. The most common site of distant metastasis is the lung. In a single series of 289 patients who developed recurrences after initial surgery, 16% died of cancer at a median time of 5 years following recurrence.[2]

The prognosis for patients with clinically detectable recurrences is generally poor, regardless of cell type.[3] Those patients who recur with local or regional tumor detected only by I131 scan, however, have a better prognosis.[4] The selection of further treatment depends on many factors, including cell type, uptake of I131, prior treatment, site of recurrence, and individual patient considerations. Surgery with or without I131 ablation can be useful in controlling local recurrences, regional node metastases, or, occasionally, metastases at other localized sites.[5] Approximately 50% of the patients operated on for recurrent tumors can be rendered free of disease with a second operation.[3] Local and regional recurrences detected by I131 scan and not clinically apparent can be treated with I131 ablation and have an excellent prognosis.[6]

Up to 25% of recurrences and metastases from well-differentiated thyroid cancer may not show I131 uptake. For these patients, other imaging techniques shown to be of value include imaging with thallium-201, magnetic resonance imaging, and pentavalent dimercaptosuccinic acid.[7] When recurrent disease does not concentrate I131, or disease recurs after I131 ablation, sorafenib has been approved by the U.S. Food and Drug Administration as a treatment option.

A phase III randomized, double-blind, placebo-controlled study (DECISION [NCT00984282]) evaluated the activity of sorafenib, an orally active, multityrosine kinase inhibitor in patients with progressive iodine-refractory differentiated thyroid cancer.[8] In the trial, 417 patients with locally advanced or metastatic radioactive iodine-refractory thyroid cancer (papillary, follicular [including Hürthle cell], and poorly differentiated varieties) who had progressed within the past 14 months were randomly assigned to sorafenib (400 mg twice daily) versus placebo. Prior chemotherapy, thalidomide, or targeted therapy were excluded.[8][Level of evidence: 1iDiii

  • The median progression-free survival in the sorafenib versus placebo groups was 10.8 versus 5.8 months (hazard ratio (HR), 0.59; 95% confidence interval (CI), 0.45–0.76; P < .001).
  • Overall survival (OS) was not significantly improved (HR, 0.80; 95% CI, 0.54–1.19; P = .14, one-sided P-value), but the median OS had not been reached at the time of primary analysis data cutoff and crossover was allowed.
  • Objective response rates (all partial) were 12.2% in the sorafenib group compared with 0.5% in the placebo group. Median time-to-progression was 11.1 months in the sorafenib group compared with 5.7 months in the placebo group (HR, 0.56; 95% CI, 0.43–0.72; P < .001).
  • Adverse events (AEs) occurred in 98.6% of patients treated with sorafenib and 87.6% of patients treated with placebo. The most frequent AEs in the sorafenib group were hand-foot skin reactions (76.3%), diarrhea (68.6%), alopecia (67.1%), and rash or desquamation (50.2%). Most events were grade 1 or 2 in severity. Seven squamous cell carcinomas of the skin occurred in the sorafenib group.

External-beam or intraoperative radiation therapy can be useful in controlling symptoms related to local tumor recurrences.[9] Systemic chemotherapy can be considered. Chemotherapy has been reported to produce occasional objective responses, usually of short duration.[4,10]

Patients unresponsive to I131 should also be considered candidates for clinical trials testing new approaches to this disease.

Treatment options under clinical evaluation:

Clinical trials evaluating new treatment approaches to this disease should also be considered for these patients. Oral inhibitors of vascular endothelial growth-factor receptors are under clinical evaluation.[11][Level of evidence: 2Dii]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent thyroid cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.


  1. Ross DS: Long-term management of differentiated thyroid cancer. Endocrinol Metab Clin North Am 19 (3): 719-39, 1990. [PUBMED Abstract]
  2. Mazzaferri EL, Jhiang SM: Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med 97 (5): 418-28, 1994. [PUBMED Abstract]
  3. Goretzki PE, Simon D, Frilling A, et al.: Surgical reintervention for differentiated thyroid cancer. Br J Surg 80 (8): 1009-12, 1993. [PUBMED Abstract]
  4. De Besi P, Busnardo B, Toso S, et al.: Combined chemotherapy with bleomycin, adriamycin, and platinum in advanced thyroid cancer. J Endocrinol Invest 14 (6): 475-80, 1991. [PUBMED Abstract]
  5. Pak H, Gourgiotis L, Chang WI, et al.: Role of metastasectomy in the management of thyroid carcinoma: the NIH experience. J Surg Oncol 82 (1): 10-8, 2003. [PUBMED Abstract]
  6. Coburn M, Teates D, Wanebo HJ: Recurrent thyroid cancer. Role of surgery versus radioactive iodine (I131) Ann Surg 219 (6): 587-93; discussion 593-5, 1994. [PUBMED Abstract]
  7. Mallin WH, Elgazzar AH, Maxon HR 3rd: Imaging modalities in the follow-up of non-iodine avid thyroid carcinoma. Am J Otolaryngol 15 (6): 417-22, 1994 Nov-Dec. [PUBMED Abstract]
  8. Brose MS, Nutting CM, Jarzab B, et al.: Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet 384 (9940): 319-28, 2014. [PUBMED Abstract]
  9. Vikram B, Strong EW, Shah JP, et al.: Intraoperative radiotherapy in patients with recurrent head and neck cancer. Am J Surg 150 (4): 485-7, 1985. [PUBMED Abstract]
  10. Shimaoka K, Schoenfeld DA, DeWys WD, et al.: A randomized trial of doxorubicin versus doxorubicin plus cisplatin in patients with advanced thyroid carcinoma. Cancer 56 (9): 2155-60, 1985. [PUBMED Abstract]
  11. Sherman SI, Wirth LJ, Droz JP, et al.: Motesanib diphosphate in progressive differentiated thyroid cancer. N Engl J Med 359 (1): 31-42, 2008. [PUBMED Abstract]
  • Updated: February 25, 2015