Variant-Based Management of Papillary Thyroid Cancer

Commentary by Lead Author Mingzhao Xing, MD, PhD and Thomas J. Giordano, MD, PhD

Patients with follicular-variant papillary thyroid cancer (FVPTC) overall have the least aggressive form of this disease, compared with patients with conventional PTC (CPTC) and tall-cell PTC (TCPTC) variants. The findings may help avoid overtreatment of largely nonaggressive tumors with the FVPTC variant, the study authors noted in the Journal of Clinical Endocrinology and Metabolism.

thyroid pictured as a puzzle, surgeon's hands

“The main finding of this large multicenter study is that FVPTC generally has a significantly better prognosis in virtually all the clinicopathological risk categories and in clinical outcomes than CPTC and TCPTC,” said lead author Mingzhao Xing, MD, PhD, Professor of Medicine, Oncology, Pathology, and Cellular & Molecular Medicine; Director, The Johns Hopkins Thyroid Tumor Center; Chief, Laboratory for Cellular and Molecular Thyroid Research, at Johns Hopkins University School of Medicine in Baltimore, MD.

“This suggests that FVPTC and CPTC, the most common two PTC variants, should be generally treated differently, with the former being generally less aggressively treated, as opposed to having FVPTC and CPTC treated indiscriminately in many practices of today,” Dr. Xing said.

“This is a well-powered study that confirms the most common histological variants of papillary carcinoma have distinct biological and clinical properties,” commented Thomas J. Giordano, MD, PhD, who is Howard Clay Bryant Professor of Pathology and Professor of Internal Medicine as well as Director of the Division of Molecular and Genomic Pathology at the University of Michigan Health System, Ann Arbor, MI. “At its core, this is a pathology study, and the results validate thyroid pathologist’s efforts over decades in developing these established variants.”

International Multicenter Cohort
The study involved an international multicenter cohort of patients with 6,282 PTC (4,799 females and 1,483 males; median age, 44 years) from 26 medical centers and the TCGA database in North America, South America, Asia, Middle East, and Europe. The authors characterized and compared the clinicopathological characteristics of the following three major PTC variants: CPTC (n=4702; 74.8%), FVPTC (n=1126; 17.9%), and TCPTC (n=239; 3.8%).

Key Findings
The prevalence of high-risk parameters differed significantly between the three variants, with TCPTC linked to the highest prevalence and FVPTC having the lowest prevalence of these parameters (Table). The CPTC variant was linked to intermediate prevalence rates.

clinicopathological characteristics among patients, 3 variants of papillary thyroid cancer
The CPTC and TCPTC variants were linked to a more than 3-fold and 14-fold increased risk for death over the FVPTC variant (hazard ratios, 3.44 and 14.96, respectively). Similarly, Kaplan-Meier survival analyses showed that the patients with FVPTC had the best prognosis, followed by patients with the CPTC variant, and with the worst prognosis found in patients with TCPTC. The statistical differences between the variants were particularly marked among patients age 45 years and older.

Clinical Implications of the Findings
“To accurately stratify the prognostic risk of thyroid cancer is an important step in individualized management of PTC and in avoiding the commonly seen overtreatment of this cancer,” Dr. Xing said. “Taking PTC variant-differentiated risk into the assessment will help improve the efficiency of this effort. It should be noted, though, the findings of this study only provide a general guidance on the differentiation between FVPTC and other PTC variants; specific clinical setting and scenario are always important to consider in the management of an individual patient.”

Are Validation Studies Necessary?
Dr. Xing said that while it is always helpful to have findings validated in another study, “in this case, however, the present study is extremely large and balanced, which should be well representative. Moreover, it may not be easy practically to have a similar study with the same large scale,” Dr. Xing said.

“The results from this study fit extremely well with the recent TCGA (The Cancer Genome Atlas) study of papillary carcinoma, which demonstrated the classical, follicular and tall cell variants have distinct biological characteristics and genetic drivers,” said Dr. Giordano, who was co-chair of the TCGA study. “The clinical implications are profound, with histologic PTC subtype being essential information required for optimal risk assessment and personalized patient care.”

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