Recurrence and Survival

Frequency of Recurrence

Kaplan-Meier survival curves of interaction of BRAF V600E mutation with age affecting disease-free probability in patients with papillary thyroid cancer1

A combination of factors from these different categories can have additive effects on risk for recurrence. For example, the combination of older age and the presence of BRAF V600E are associated with greater risk for recurrence than either of these risk factors alone.1

Cancer recurrence in patients who have been treated for this malignancy remains a concern.

Results from a study in which 574 patients with well-differentiated thyroid cancer were followed up long-term, indicated a 30-year recurrence of 13%, and a median time to recurrence of 7 months.2

Multiple factors contribute to risk for recurrence in patients with well-differentiated thyroid cancer. These factors can be divided into 3 broad categories, all of which increase the risk for recurrence.

Those related to the patient

  • Older age at diagnosis3,4
  • Male sex5

Those related to the tumor

  • Larger size6,7
  • Size/number of lymph nodes8
  • Capsular invasion9
  • Vascular invasion10
  • Extrathyroidal extension9
  • Metastatic disease3,6,7,9
  • Presence of the B-type kinase (BRAF) V600E11,11,12
  • Presence of the telomerase reverse transcriptase (TERT) mutation promoter1

Those related to treatment

  • Lobectomy or hemi-thyroidectomy rather than total thyroidectomy13,14
  • Whether or not radioiodine ablation is carried out following thyroidectomy15


Extent of surgery and risk for recurrence in patients with papillary thyroid cancer11

There is also an interaction between tumor characteristics and management approach for initial surgery. This was demonstrated by results from 52,173 patients who underwent surgery for papillary thyroid cancer. Of these, 43,227 patients had a total thyroidectomy and 8,946 underwent lobectomy. For tumors <1 cm, there was no significant difference between recurrence rates for the 2 surgical approaches; but for those >1 cm, recurrence occurred significantly more often with lobectomy.11

Thyroid Cancer Survival

The risks for mortality in patients with thyroid cancer are strongly influenced by type and stage of disease. The 10-year overall relative survival rates for U. S. patients with papillary, follicular, Hürthle cell, medullary, and undifferentiated/anaplastic carcinoma was 93%, 85%, 76%, 75%, and 14%, respectively.13 The 5-year survival of patents with localized thyroid cancer is >99% while that for cancer with distant metastases is 54.1%.14

While the prognosis for most people with thyroid cancer is very good, the rate of recurrence or persistence can be up to 30%, and recurrences can occur even decades after the initial treatment.15

It is also clear that radioiodine ablation following total thyroidectomy is associated with improved overall survival in specific patient populations. In a recent study, overall survival was assessed among 21,780 patients with intermediate-risk papillary thyroid cancer, as defined by the American Thyroid Association risk and American Joint Commission on Cancer (disease stage T3, N0, M0, or Mx, and T1-3, N1, M0, or Mx). Patients were treated with (N=15,418) or without (N=6,452) radioiodine ablation and followed for an average of 7 years.17

Study results indicated that radioiodine ablation was associated with improved overall survival among all patients (P<.001) and for the subgroups of patients younger than 45 years (P=.002) and aged 65 years and older (P=.008).17

Unadjusted overall survival difference for all patients with intermediate-risk papillary thyroid cancer, with and without radioiodine ablation use17


  1. Xing M, Liu R, Liu X, et al. BRAF V600E and TERT promoter mutations cooperatively identify the most aggressive papillary thyroid cancer with highest recurrence. J Clin Oncol. 2014;32:2718-2726.
  2. Palme CE, Waseem Z, Raza SN, Eski S, Walfish P, Freeman JL. Management and outcome of recurrent well-differentiated thyroid carcinoma. Arch Otolaryngol Head Neck Surg. 2004;130:819-824.
  3. Falvo L, Catania A, D’Andrea V, Marzullo A, Giustiniani MC, De Antoni E. Prognostic importance of histologic vascular invasion in papillary thyroid carcinoma. Ann Surg. 2005;241:640-646.
  4. Hsieh SH, Chen ST, Hsueh C, Chao TC, Lin JD. Gender-specific variation in the prognosis of papillary thyroid cancer TNM stages II to IV. Int J Endocrinol. 2012;2012:379097.
  5. Ito Y, Kudo T, Kobayashi K, Miya A, Ichihara K, Miyauchi A. Prognostic factors for recurrence of papillary thyroid carcinoma in the lymph nodes, lung, and bone: analysis of 5,768 patients with average 10-year follow-up. World J Surg. 2012;36:1274-1278.
  6. Vaisman F, Shaha A, Fish S, Michael Tuttle R. Initial therapy with either thyroid lobectomy or total thyroidectomy without radioactive iodine remnant ablation is associated with very low rates of structural disease recurrence in properly selected patients with differentiated thyroid cancer. Clin Endocrinol (Oxf). 2011;75:112-119.
  7. Randolph GW, Duh QY, Heller KS, LiVoisi VA, Mandel SH, Steward DL, et al. The prognostic significance of nodal metasteses from papillary thyroid carcinoma can be stratified based on the size and number of metastatic lymph nodes, as well as the presence of extranodal extension. Thyroid. 2012;11:1144-1152.
  8. Mercante G, Frasoldati A, Pedroni C, et al. Prognostic factors affecting neck lymph node recurrence and distant metastasis in papillary microcarcinoma of the thyroid: results of a study in 445 patients. Thyroid. 2009;19:707-716.
  9. Xing M, Alzahrani AS, Carson KA, et al. Association between BRAF V600E mutation and recurrence of papillary thyroid cancer. J Clin Oncol. 2015;33:42-50.
  10. Gao WL, Wie LL, Chao YG, Wie L, Song TL. Prognostic prediction of BRAF(V600E) and its relationship with sodium iodide symporter in classic variant of papillary thyroid carcinomas. Clin Lab. 2012;58:919-926.
  11. Bilimoria KY, Bentrem DJ, Ko CY, et al. Extent of surgery affects survival for papillary thyroid cancer. Ann Surg. 2007;246:375-381.
  12. Hurtado-López LM, Melchor-Ruan J, Basurto-Kuba E, et al. Low-risk papillary thyroid cancer recurrence in patients treated with total thyroidectomy and adjuvant therapy vs. patients treated with partial thyroidectomy. Cir Cir. 2011;79:118-125.
  13. Hundahl SA, Fleming ID, Fremgen AM, et al. A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985-1995. Cancer.  1998;83:2638-2648.
  14. SEER. Thyroid cancer. Accessed Nov 4, 2015.
  15. ThyCa: Thyroid Cancer. 2015. Accessed Jan 8, 2016.
  16. Leung AM, Dave S, Lee SL, Campion FX, Garber JR, Pearce EN. Factors determining the persistence or recurrence of well-differentiated thyroid cancer treated by thyroidectomy and/or radioiodine in the Boston, Massachusetts area: a retrospective chart review. Thyroid Res. 2011;4:9.
  17. Ruel E, Thomas S, Dinan M, Perkins JM, Roman SA, Sosa JA. Adjuvant radioactive iodine therapy is associated with improved survival for patients with intermediate-risk papillary thyroid cancer. J Clin Endocrinol Metab. 2015;100:1529-1536.

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Thyrogen® (thyrotropin alfa for injection) 0.9 mg/mL after reconstitution



There have been reports of death in non-thyroidectomized patients and in patients with distant metastatic thyroid cancer in which events leading to death occurred within 24 hours after administration of Thyrogen.

Caution should be exercised in patients who have substantial thyroid tissue still in situ or functional thyroid cancer metastases, specifically in the elderly and those with a known history of heart disease.

Hospitalization for administration of Thyrogen and post-administration observation in patients at risk should be considered.

There are post marketing reports of stroke in young women with risk factors for stroke, and neurological findings suggestive of stroke (e.g., unilateral weakness) occurring within 72 hours of Thyrogen administration in patients without known central nervous system metastases.

Patients should be well-hydrated prior to treatment with Thyrogen.

Sudden, rapid and painful enlargement of residual thyroid tissue or distant metastases can occur following treatment with Thyrogen.

Pretreatment with glucocorticoids should be considered for patients in whom tumor expansion may compromise vital anatomic structures.


The most common adverse reactions reported in clinical trials were nausea and headache.


Pregnancy Category C: Animal reproduction studies have not been conducted with Thyrogen. It is also not known whether Thyrogen can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Thyrogen should be given to a pregnant woman only if clearly needed.

Nursing Mothers: It is not known whether the drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Thyrogen is administered to a nursing woman.

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

Geriatric Use: Results from controlled trials do not indicate a difference in the safety and efficacy of Thyrogen between adult patients less than 65 years and those over 65 years of age.

Renal Impairment: Elimination of Thyrogen is significantly slower in dialysis-dependent end stage renal disease patients, resulting in prolonged elevation of TSH levels.


Thyrogen is a thyroid stimulating hormone indicated for:

Diagnostic: Use as an adjunctive diagnostic tool for serum thyroglobulin (Tg) testing with or without radioiodine imaging in the follow-up of patients with well-differentiated thyroid cancer who have previously undergone thyroidectomy.

Limitations of Use:

  • Thyrogen -stimulated Tg levels are generally lower than, and do not correlate with Tg levels after thyroid hormone withdrawal.
  • Even when Thyrogen -Tg testing is performed in combination with radioiodine imaging, there remains a risk of missing a diagnosis of thyroid cancer or underestimating the extent of the disease.
  • Anti-Tg Antibodies may confound the Tg assay and render Tg levels uninterpretable.

Ablation: Use as an adjunctive treatment for radioiodine ablation of thyroid tissue remnants in patients who have undergone a near-total or total thyroidectomy for well-differentiated thyroid cancer and who do not have evidence of distant metastatic thyroid cancer.

Limitations of Use:

  • The effect of Thyrogen on long term thyroid cancer outcomes has not been determined.

See full Prescribing Information for more details.