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ONCOLOGY. Vol. 16 No. 3
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The Angelos Article Reviewed 

Current Approaches to the Treatment of Well-Differentiated Thyroid Cancer

By

Steven I. Sherman, MD
Associate Professor of Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

| March 1, 2002

The increasing frequency of diagnosis and death of patients with follicular cell-derived carcinoma of the thyroid substantiates the need for a broad understanding of the optimal diagnostic and treatment strategies for this disease. Dr. Angelos has provided a good overview of the treatment modalities and approaches to follow-up for these patients. However, several points require additional emphasis or detail.

Prognosis and Staging

More than 1,200 patients die annually from follicular cell-derived carcinoma or the complications of its treatment, with 10-year relative survival rates of about 95% and 90% for papillary and nonoxyphilic follicular carcinoma, respectively.[1,2] Recurrence rates are usually at least twice that of mortality rates for these patients. Major prognostic factors at diagnosis associated with increased risk for eventual disease-related mortality include larger tumor size, invasion of the primary tumor into extrathyroidal tissues, extracervical metastases, and older age.

Similarly, disease recurrence or progression is associated with these parameters, but age is a double-edged sword; ie, the youngest patients experience high recurrence and progression rates as well. Multiple minor factors have also been identfied, but there exists far less agreement about the importance of variables such as multifocality and locoregional nodal involvement. Certain histologic subtypes may represent more aggressive disease; eg, the tall cell variant of papillary carcinoma or the oxyphilic (Hürthle cell) variant of follicular carcinoma.

Microscopic, immunohistochemical, and molecular features that have been associated with a greater risk of either recurrence or death include increased tumor vascularity, aneuploidy, increased epidermal growth factor (EGF)-receptor and decreased thyroid-stimulating hormone (TSH)-receptor status, and the presence of the ret/PTC3 oncogene isoform.[3] The variation in the appearance and behavior of the various subtypes of follicular cell-derived carcinoma makes the phrase "well-differentiated thyroid carcinoma" archaic and may lead to underestimates of the potential for morbidity and mortality.

Whether to use prognostic staging and how to select among the various approaches to staging remain significant challenges for the practicing clinician. In addition to the three risk group classifications cited by Dr. Angelos, numerous other approaches have been proposed, including those developed by the American Joint Commission on Cancer (AJCC), European Organization for Research and Treatment of Cancer (EORTC), Clinical Class, Ohio State University, National Thyroid Cancer Treatment Cooperative Study, Mayo Clinic (MACIS, for metastases, age, completeness of surgery, invasion of cancer, size), and Lahey Clinic (AMES, for age, metastases, extent, size).[4] Two recent studies demonstrated the superior predictive value of the AJCC approach compared with the Clinical Class, Ohio State, MACIS, and AMES strategies, leading to the widespread recognition and incorporation of the AJCC classification strategy into two consensus treatment guidelines.[5,6]

Role of TSH-Suppression Therapy

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