The impact of distant metastases at presentation on prognosis in patients with differentiated carcinoma of the thyroid gland.

BACKGROUND Distant metastases at presentation are rare in well-differentiated thyroid cancer (WDTC). The objective of this study was to report outcomes for patients presenting with distant metastases managed by thyroidectomy and radioactive iodine (RAI) therapy. METHODS Fifty-two patients with distant metastases from thyroid cancer diagnosed before thyroid surgery (n=32) or on a postoperative RAI scan after thyroid surgery (n=20) were identified from a database of patients with WDTC treated between 1985 and 2005. The median age was 58 years (range 12-83 years), with a male-to-female ratio of 3:2. Forty-seven patients (90%) had total thyroidectomy and two (4%) had thyroid lobectomy, and three patients (6%) were found to be unresectable. Distant metastases were classified into pulmonary and extrapulmonary. Overall survival (OS), disease-specific survival (DSS), and locoregional recurrence-free survival were calculated by the Kaplan-Meier method. Factors predictive of the outcome were determined by univariate and multivariate analyses. RESULTS Thirty-nine patients (75%) were diagnosed with pulmonary metastases alone and 13 (25%) with extrapulmonary metastases. The sites of extrapulmonary metastases were bone in nine, mediastinum in one, pyriform sinus in one and skin in one, and one patient had synchronous lung, bone, and intracerebral metastases. After thyroid surgery, 47 patients (90%) were treated with RAI alone, and 2 patients had external beam radiation in addition to RAI. With a median follow-up after surgery of 78.5 months, the 5-year OS and DSS were 65% and 68%, respectively. Twenty-nine patients (56%) died during follow-up, of whom 24 (46%) died of thyroid cancer. Six patients (12%) developed recurrent disease in the lateral neck, and three patients (6%) developed recurrence in the thyroid bed. Over 45 years, follicular pathology and extrapulmonary metastases were predictive of lower 5-year DSS (56% vs. 100%, p<0.001; 50% vs. 70%, p=0.004; and 46% vs. 75%, p=0.013, respectively). CONCLUSION Approximately half of patients with WDTC presenting with distant metastases die of disease within 5 years of initial diagnosis despite thyroid surgery and RAI. Age over 45 years, extrapulmonary metastases, and follicular pathology were significant predictors of the poor outcome.

[1]  J. Shah,et al.  Prognostic indicators of outcomes in patients with distant metastases from differentiated thyroid carcinoma. , 2003, Journal of the American College of Surgeons.

[2]  I. Sugitani,et al.  Papillary thyroid carcinoma with distant metastases: survival predictors and the importance of local control. , 2008, Surgery.

[3]  J. Mihailovič,et al.  Metastatic differentiated thyroid carcinoma: clinical management and outcome of disease in patients with initial and late distant metastases , 2009, Nuclear medicine communications.

[4]  P. Grigsby,et al.  Prognostic factors in patients with well-differentiated thyroid cancer presenting with pulmonary metastasis. , 2008, Cancer biotherapy & radiopharmaceuticals.

[5]  M. A. García-Cabezas,et al.  The oncogene BRAF V600E is associated with a high risk of recurrence and less differentiated papillary thyroid carcinoma due to the impairment of Na+/I- targeting to the membrane. , 2006, Endocrine-related cancer.

[6]  J. Shah,et al.  Differentiated thyroid cancer presenting initially with distant metastasis. , 1997, American journal of surgery.

[7]  J. Mihailovič,et al.  Differentiated thyroid carcinoma with distant metastases: probability of survival and its predicting factors. , 2007, Cancer biotherapy & radiopharmaceuticals.

[8]  G. Masarotto,et al.  Different features of pulmonary metastases in differentiated thyroid cancer: natural history and multivariate statistical analysis of prognostic variables. , 1993, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[9]  Stephanie L. Lee,et al.  Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. , 2009, Thyroid : official journal of the American Thyroid Association.

[10]  Jandee Lee,et al.  Differentiated Thyroid Carcinoma Presenting With Distant Metastasis at Initial Diagnosis: Clinical Outcomes and Prognostic Factors , 2010, Annals of surgery.

[11]  E. Bergstralh,et al.  Predicting outcome in papillary thyroid carcinoma: development of a reliable prognostic scoring system in a cohort of 1779 patients surgically treated at one institution during 1940 through 1989. , 1993, Surgery.

[12]  E. Baudin,et al.  Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy. , 2006, The Journal of clinical endocrinology and metabolism.

[13]  J. Juang,et al.  Factors related to the survival of papillary and follicular thyroid carcinoma patients with distant metastases. , 1999, Thyroid : official journal of the American Thyroid Association.

[14]  C. Harmer,et al.  Differentiated thyroid carcinoma with distant metastases at presentation: prognostic factors and outcome , 2005, Clinical endocrinology.

[15]  G. Guiraudon,et al.  Pulmonary metastases in differentiated thyroid carcinoma. Study of 58 cases with implications for the primary tumor treatment , 1984, Cancer.

[16]  M. Schlumberger,et al.  Radioactive iodine treatment and external radiotherapy for lung and bone metastases from thyroid carcinoma. , 1996, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[17]  J. Watkinson,et al.  The British Thyroid Association guidelines for the management of thyroid cancer in adults , 2004, Nuclear medicine communications.

[18]  M. Schlumberger,et al.  [European consensus on the management of patients with differentiated carcinoma of the thyroid from follicular epithelium]. , 2008, Vestnik khirurgii imeni I. I. Grekova.

[19]  B. Cady,et al.  An expanded view of risk-group definition in differentiated thyroid carcinoma. , 1988, Surgery.

[20]  J. Shah,et al.  Risk group stratification and prognostic factors in papillary carcinoma of thyroid , 1996, Annals of Surgical Oncology.

[21]  Paula D. Bos,et al.  Metastasis: from dissemination to organ-specific colonization , 2009, Nature Reviews Cancer.

[22]  J. Massagué,et al.  Genetic determinants of cancer metastasis , 2007, Nature Reviews Genetics.

[23]  S. Dinneen,et al.  Distant metastases in papillary thyroid carcinoma: 100 cases observed at one institution during 5 decades. , 1995, The Journal of clinical endocrinology and metabolism.