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Differential Clinicopathological Risk and Prognosis of Major Papillary Thyroid Cancer Variants
Xiaoguang Shi1, Rengyun Liu1, Fulvio Basolo1
1Laboratory for Cellular and Molecular Thyroid Research, Division of Endocrinology, Diabetes & Metabolism, Department of Medicine (X.Shi., R.L., X.Shen., D.T., M.X.), Johns Hopkins University School of Medicine, Baltimore, MD 21287; Department of Surgery, Division of Pathology (F.B., R.G.), 56126 Pisa, Italy; The Endocrine Institute and The Liaoning Provincial Key Laboratory of Endocrine Diseases, Department of Endocrinology and Metabolism (H.G., Z.S., W.T.), The First Hospital of China Medical University, Shenyang, Liaoning Province 110001, China; Endocrine Surgery (T.J.M.), University Medical Center, Johannes Gutenberg University Mainz, 55101 Mainz, Germany; Human Cancer Genomic Research (K.A.K.), Research Centre, King Faisal Specialist Hospital and Research Centre, Riyadh 12713, Kingdom of Saudi Arabia; Fondazione Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Policlinico, Milan, and Department of Pathophysiology and Transplantation (L.E., C.C.), University of Milan, 20122 Milan Italy; Endocrine Oncology Branch, Center for Cancer Research (E.K.), National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892; Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (A.C., B.J.), 44-101 Gliwice, Poland; Department of Molecular Endocrinology (B.B., V.S.), Institute of Endocrinology, Prague 11694, Czech Republic; Institute of Molecular Pathology and Immunology (Manuel Sobrinho-Simões, M.S.S.; Paula Soares, P.So.), University of Porto (Ipatimup) and Medical Faculty of the University of Porto, 4200-319 Porto, Portugal; College of Medicine (Y.K.S., T.Y.K.), University of Ulsan College of Medicine, Seoul, South Korea; Department of Pathology (S.C.; S.L.A.), University Health Network, Toronto, ON M5G 2C4 Canada; Endocrine Unit, Department of Clinical and Experimental Medicine (D.V., R.E.), World Health Organization, Collaborating Center for the Study and Treatment of Thyroid Diseases and Other Endocrine and Meta
Context:
Individualized management, incorporating papillary thyroid cancer (PTC) variant-specific risk, is conceivably a useful treatment strategy for PTC, which awaits comprehensive data demonstrating differential risks of PTC variants to support.
Objective:
This study sought to establish the differential clinicopathological risk of major PTC variants: conventional PTC (CPTC), follicular-variant PTC (FVPTC), and tall-cell PTC (TCPTC).
Methods:
This was a retrospective study of clinicopathological outcomes of 6282 PTC patients (4799 females and 1483 males) from 26 centers and The Cancer Genome Atlas in 14 countries with a median age of 44 years (interquartile range, 33-56 y) and median follow-up time of 37 months (interquartile range, 15-82 mo).
Results:
The cohort consisted of 4702 (74.8%) patients with CPTC, 1126 (17.9%) with FVPTC, and 239 (3.8%) with TCPTC. The prevalence of high-risk parameters was significantly different among the three variants, including extrathyroidal invasion, lymph node metastasis, stages III/IV, disease recurrence, mortality, and the use (need) of radioiodine treatment (all P < .001), being highest in TCPTC, lowest in FVPTC, and intermediate in CPTC, following an order of TCPTC > CPTC ≫ FVPTC. Recurrence and mortality in TCPTC, CPTC, and FVPTC were 27.3 and 6.7%, 16.1 and 2.5%, and 9.1 and 0.6%, corresponding to events per 1000 person-years (95% confidence interval [CI]) of 92.47 (64.66-132.26) and 24.61 (12.31-49.21), 34.46 (30.71-38.66), and 5.87 (4.37-7.88), and 24.73 (18.34-33.35) and 1.68 (0.54-5.21), respectively. Mortality hazard ratios of CPTC and TCPTC over FVPTC were 3.44 (95% CI, 1.07-11.11) and 14.96 (95% CI, 3.93-56.89), respectively. Kaplan-Meier survival analyses showed the best prognosis in FVPTC, worst in TCPTC, and intermediate in CPTC in disease recurrence-free probability and disease-specific patient survival. This was particularly the case in patients at least 45 years old.
Conclusion:
This large multicenter study demonstrates differential prognostic risks of the three major PTC variants and establishes a unique risk order of TCPTC > CPTC ≫ FVPTC, providing important clinical implications for specific variant-based management of PTC.
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