RISK STRATIFICATION METHOD FOR THYROID CANCER

Sunarto ReksoprawiroDivision of Head & Neck Surgery, Department of SurgeryFaculty of Medicine-Airlangga University/ Dr. Soetomo Hospital Surabaya, Indonesia 

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

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

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

• 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

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

STAGING SYSTEMS1. European Organization for Research and Treatment of Cancer (EORTC)2.  Mayo Clinic (Age, Grade, Extent, Size or AGES)3. Lahey Clinic (Age, Metastases, Extent, Size or AMES)4. University of Chicago (Clinical Class)5. Karolinska Hospital and Institute (DNA ploidy, Age, Metastases, Extent,

Size or DAMES)6. Mayo Clinic (Metastases, Age, Complete resection, Invasion, Size or

MACIS)7. University of Bergen (Sex, Age, Grade or SAG)8. Ohio State University (OSU)9. Noguchi Thyroid Clinic (Noguchi) 10. Memorial Sloan Kettering (Grade, Age, Metastases, Extent, Size or

GAMES)11. University of Munster (Munster)12. National Thyroid Cancer Treatment Cooperative Study (NTCTCS)13. University of Alabama and M.D. Anderson (UAB &MDA)14. Virgen de la Arrixaca University at Murcia (Murcia)15. AJCC/UICC 6th edition TNM (TNM)16. Cancer Institute Hospital in Tokyo (CIH)17. Ankara Oncology Training and Research Hospital in Turkey (Ankara)18. Degroot

• 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.

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

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.

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

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.

• 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

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

Very Low risk Low Risk Intermediate Risk High Risk

Age at diagnosis < 45 years < 45 years Young patients (< 45 years)Classic PTC > 4 cmOr vascular invasionOr extrathyroidal extensionOr worrisome histology ofany size‡

> 45 years

Primary tumor size < 1 cm 1–4 cm Older patients (> 45 years)Classic PTC < 4 cmOr extrathyroidal extensionOr worrisome histology< 1–2 cm confi ned to thethyroid‡

> 4 cm classic PTC

Histology Classic PTC, confined to the thyroid gland*

Classic PTC, confined tothe thyroid gland*

Histology in conjunction with age as above

Worrisome histology> 1–2 cm‡

Completeness of resection

Complete resection Complete resection Complete resection Incomplete tumor resection

Lymph node involvement

None apparent Present or absent† Present or absent† Present or absent†

Distant metastasis None apparent None apparent None apparent Present

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

Pathology review

USG neck

Evidence of lobectomy + isthmectomy or large thyroid remnant

Unfavorable histology Low risk group (using presurgery criteria)

Multifocal diseasePositive margin

Age > 50 years observe Male sex Nodule > 4

cm Nodule

metastasis

Completion thyroidectomy

REVISION SURGERY

If USG insignificant thyroid remnant

RI scan

Significant uptake >15% Low uptake <15%%

Completion thyroidectomy RI ablation

Frequency of thyroid carcinomaDr.Soetomo Hospital Surabaya (2007-2011)

N= 284 cases

Fig.1. Sex distribution

n = 284

Fig.2. Sex and age distribution

n = 284

Fig.3. Metastasesn = 284

Prognostic Factors

AMESLow risk

Age : < 40 yrs (male); < 50 yrs (female)

Metastases : None Extension : No extrathyroid extension Size : < 4 cm

Fig.4. Risk stratification

n = 284

Fig.5. Treatment

n = 284

Fig.6. Surgical treatment

n = 221

Fig.7. Surgical complication

0.51%

n = 1950.51%

0.51%

0.51%

0.51%

Fig.8. Completion thyroidectomy

n= 57

Fig.9. Histopathology

n = 284

Fig.10. Mortality in hospital

n = 284

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.

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.

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.

Thank you