Risk stratification method for thyroid cancer

1. Sunarto Reksoprawiro Division of Head & Neck Surgery, Department of Surgery Faculty of Medicine-Airlangga University/ Dr. Soetomo Hospital Surabaya, Indonesia Risk stratification method for thyroid cancer

2. INTRODUCTION THYROID CANCER • Incidence : 1.2 to 2.6 per 100,000 (men) and 2.0 to 3.8 per 100,000 (women) • >90% of tumors are differentiated thyroid cancer • Some prognostic scoring systems do not differ between PTC and FTC

3. PTC accounts for at least 70% of all DTC • 10% of patients would eventually die of the disease and an even greater proportion would face the morbidity of recurrences. • A number of studies have identified various clinicopathologic predictors for PTC and devised risk-group stratification or staging systems

4. Age, gender, histological type, tumour size and extrathyroidal invasion have been found previously to be associated with a poor clinical outcome • The prognostic impact of regional lymph node metastases is still a controversial issue • Distant metastases is a recognized factor for a poor prognosis

5. There are conflicting thoughts over different aspects of treatment of differentiated thyroid cancer • The lack of consensus stems due to the absence of concrete data from randomized controlled trials • Surgery with or without radio-iodine therapy forms the mainstay of treatment of differentiated thyroid cancers

6. STAGING SYSTEMS • Many scoring or staging systems have been developed during the last two decades • The most commonly used staging classifications are AMES , AGES , MACIS , EORTC , and UICC-TNM

7. STAGING SYSTEMS • European Organization for Research and Treatment of Cancer (EORTC) •  Mayo Clinic (Age, Grade, Extent, Size or AGES) • Lahey Clinic (Age, Metastases, Extent, Size or AMES) • University of Chicago (Clinical Class) • Karolinska Hospital and Institute (DNA ploidy, Age, Metastases, Extent, Size or DAMES) • Mayo Clinic (Metastases, Age, Complete resection, Invasion, Size or MACIS) • University of Bergen (Sex, Age, Grade or SAG) • Ohio State University (OSU) • Noguchi Thyroid Clinic (Noguchi) • Memorial Sloan Kettering (Grade, Age, Metastases, Extent, Size or GAMES) • University of Munster (Munster) • National Thyroid Cancer Treatment Cooperative Study (NTCTCS) • University of Alabama and M.D. Anderson (UAB &MDA) • Virgen de la Arrixaca University at Murcia (Murcia) • AJCC/UICC 6th edition TNM (TNM) • Cancer Institute Hospital in Tokyo (CIH) • Ankara Oncology Training and Research Hospital in Turkey (Ankara) • Degroot

8. There was no difference in the abilities of the top five classifications (AGES, TNM, EORTC, MACIS and AMES) to predict the prognosis for patients with differentiated thyroid carcinoma, and no statistically significant superiority of any system over the TNM classification was found • Brierley JD, Panzarella T, Tsang RW, Gospodarowicz MK & O’Sullivan B. A comparison of different staging systems predictability of patient outcome. Cancer 1997;79:2414–2423.

9. There is no difference in tumor-specific survival between PTC and FTC when accounting for the presence of metastases, age, tumour size, and the presence of extrathyroidal invasion • Verburg A, Mäder U, Luster M & Reiners C. Primary tumor diameter as a risk factor for advanced disease features of differentiated thyroid carcinoma. Clin Endocrinol 2009;71: 291–297

10. Age at presentation is a well-established strong prognostic factor for differentiated thyroid carcinoma • Cady B & Rossi R. An expanded view of risk-group definition in differentiated thyroid carcinoma. Surgery 1988;104 :947–953.

11. Gender proved to be of prognostic value for disease-free survival, which was shorter for males than for females • Jukkola A, Bloigu R, Ebeling T & Salmela P. Prognostic factors in differentiated thyroid carcinomas and their implications for current staging classifications. Endocrine-Related Cancer 2004;11:571–579

12. Tumor extension beyond the thyroid capsule (pT4) is described as being one of the strongest prognostic factors in DTC, therefore resulting in its use in most staging systems • Lerch H, Schober O, Kuwert T & Saur HB. Survival of differentiated thyroid carcinoma studied in 500 patients. J Clin Oncol 1997;15:2067–2075.

13. In some, but not all, studies, local lymph node involvement has been associated with an increased risk of tumour recurrence and also with DTC-related mortality • Mazzaferri EL & Young EL. Papillarythyroid carcinoma: a 10 year follow-up report of the impact of therapy in 576 patients. Am J Med 1981;70:511–51 • In patients > 45 years of age, involvement of cervical lymph nodes was associated with a poorer prognosis in PTC and FTC patients • Passler C, Scheuba C, Prager G, Kaczirek K, Kaserer K, Zettinig G, and Niederle B. Prognostic factors of papillary and follicular thyroid cancer: difference in an iodine-replate endemic goiter region. Endocrine-Related Cancer 2004;11:131-139

14. The diameter of the primary tumour is a determinant (independent predictor) for outcome in differentiated thyroid cancer. However, the delineation between low-risk and high-risk tumour size is unsettled. • Mazzaferri & Kloos : 4 cm • Machens et al. : 2 cm • Verburg et al. : 1 cm

15. Table 1. Risk of Death From Thyroid Cancer (Tuttle et al)

16. REVISION SURGERY Pathology review USG neck Evidence of lobectomy + isthmectomy or large thyroid remnant Unfavorable histology Low risk group (using presurgery criteria) Multifocal disease Positive margin Age > 50 years observe Male sex Nodule > 4 cm Nodule metastasis Completion thyroidectomy

17. If USG insignificant thyroid remnant RI scan Low uptake <15%% Significant uptake >15% Completion thyroidectomy RI ablation

18. Frequency of thyroid carcinomaDr.Soetomo Hospital Surabaya (2007-2011) N= 284 cases

19. Fig.1. Sex distribution n = 284

20. Fig.2. Sex and age distribution n = 284

21. Fig.3. Metastases n = 284

22. Prognostic Factors • AMES Low risk • Age : < 40 yrs (male); < 50 yrs (female) • Metastases : None • Extension : No extrathyroid extension • Size : < 4 cm

23. Fig.4. Risk stratification n = 284

24. Fig.5. Treatment n = 284

25. Fig.6. Surgical treatment n = 221

26. Fig.7. Surgical complication n = 195 0.51% 0.51% 0.51% 0.51% 0.51%

27. Fig.8. Completion thyroidectomy n= 57

28. Fig.9. Histopathology n = 284

29. Fig.10. Mortality in hospital n = 284

30. SUMMARY • A number of risk-group stratification have been found useful at stratifying patients with differentiated thyroid carcinoma into risk groups • Significant risk factors were age, primary tumor size, histology, grade, local tumor extension, completeness of resection, and distant metastasis.

31. Aggressive surgical resection was recommended for all gross disease in high risk and intermediate risk patients. The standard treatment for high risk patients are total thyroidectomy followed by I131 ablation and TSH suppression with thyroxin. • Well-differentiated thyroid cancer in low risk patients has a favorable outcome and can be safely treated with unilateral thyroidectomy alone.

32. Postoperatively, the patient’s operative and pathology records should be studied to re-assess the risk-group of the patients. • Appropriate selection of surgical and adjuvant treatment should therefore be used based on prognostic factors and risk group stratification.

33. Thank you