AACE Advances in Medical and Surgical Management of Thyroid Cancer, 2015. Tampa, Florida.

AACE Advances in Medical and Surgical Management of Thyroid Cancer, 2015. Tampa, Florida. Dev Abraham MD, MRCP (UK), ECNU Professor of Medicine, Division of Endocrinology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT

1. Discuss the prevalence of DTC 2. Review of risk factors for thyroid cancer 3. The debate of increased detection vs increased incidence 4. Concerns regarding over-diagnosis and over- treatment

23 years old lady presents to the ER for evaluation of persistent neck pain following a whip lash injury sustained in a car wreck CT scan of the neck was performed Radiology report: Left thyroid lobe contains an ill defined nodule which is inadequately evaluated by this examination. Malignancy cannot be ruled out and a dedicated US study is recommended

FNA Papillary thyroid cancer

I grew up in the 4 corners region - Nevada above ground testing, my parents lived all their lives there. My father died of lung cancer and my mother has lymphoma 4 people in the same street have thyroid cancer. Is this the reason? What should I do about my daughter who is 2 years old? Is her risk for cancer increased?

Family history of thyroid cancer Family history: 10 fold increased risk. Incidence ratio: affected parent - 3.21 Sib 6.2 and for a female with affected sister 11.1 History of exposure to radiation Nodule detected in a patient with history of radiation: 30 % risk of cancer Acne, fungal scalp infection, Hodgkin s, Squamous head and neck cancers Nuclear disasters eg: Chernobyl

Extrinsic X rays Radiation I131 Iodine supplementation Westernized lifestyle Environmental pollutants PCBs, BPA, aromatic hydrocarbons USA 80,000 chemicals are present is various products only a few are even tested Intrinsic Elevated TSH (subclinical) Autoimmune thyroid disease Obesity and insulin resistance

US 13 % (Carotid vascular studies) CT 16 % MRI 16% PET scan 4-8 %

Prevalence % AGE Mazzaferri EL: NEJM 328:553, 1993

30 50 % population have thyroid nodules 100 to 150 million of US population have thyroid nodules Risk of cancer: About 4% If FNA is performed about 10-30% may require surgery depending on the quality of cytological reporting Results in massive numbers subjected to thyroid surgery What is the frequency of sub cm cancers

METANALYSIS OF THE PREVALENCES OF THYROID MICROCARCINOMAS FOUND AT AUTOPSY SERIES THYROID Volume 15, Number 2, 2005 Kovacs et al Geographical region Series Prevalence Balazs et al. (7) 1974 s Debrecen, Hungary 9/200 4.5% Sampson et al. (8) 1974 s Minnesota, USA 9/157 5.7% s Hiroshima- 196/1096 17.9% Nagasaki, Japan Fukunaga et al. (9) 1975 w Cali-Medellin, 34/607 5.6% Columbia w Hawaii, Japanese 60/248 24.2% w Ontario, Canada 6/100 6.0% w Gliwice, Poland 10/110 9.1% w Sendai, Japan 29/102 28.4% Sobrinho-Simoes 1979 s Oporto, Portugal 40/600 6.6% et al. (10) Bondeson et al. (11) 1981 s Malmö, Sweden 43/500 8.6% Harach et al. (12) 1985 w Finland 36/101 35.6% Lang et al. (13) 1987 s Hannover, Germany 63/1020 6.2% Ottino et al. (14) 1989 w La Plata, Argentína 11/100 11.0% Yamamoto et al. (15) 1990 s Tokushima, Japan 46/408 11.3% Neuhold et al. (16) 2001 w Vienna, Horn, 10/118 8.5%

THYROID CANCER: SEER 9 Incidence & U.S. Mortality 1975-2011, All Races, Both Sexes. Rates are Age- Adjusted.

Prevalence SEER On January 1, 2010, in the USA 534,973 men and women were alive who had a history of cancer of the thyroid 418,111 - females 116,862 - males

Surveillance Epidemiology & End Results (SEER - NCI) UK CANADA USA - SEER Life time risk: 0.73% of men and women born today will be diagnosed with PCT

UTAH Thyroid cancer Surveillance Epidemiology and End Results SEER- NCI

Thyroid cancer UTAH

50.22 million (2013) South Korea, Population Source World Bank Thyroid cancer is now the most common type of cancer diagnosed in South Korea. More than 40,000 people in the country were diagnosed with the disease in 2011 a figure that is more than 100 times the number of people who die from thyroid cancer, which for the past decade has been between 300 and 400 each year. Virtually all the people diagnosed with thyroid cancer are treated: roughly two thirds undergo radical thyroidectomy, and one third undergo subtotal thyroidectomy.

An analysis of insurance claims for more than 15,000 Koreans who underwent surgery showed that 11% had hypoparathyroidism and 2% had vocal-cord paralysis Despite guidelines recommending against evaluation and surgery for tumors less than 0.5 cm in diameter, one quarter of surgical patients now have tumors that fall into this category.

1-1.5% of all cancers in USA (SEER) Fifth most common cancer in women In Italy second most frequent cancer in women <45 years of age Almost in all countries, there is an apparent increase Norway and Sweden exception incidence is dropping

1350 deaths per year

Stage at Diagnosis Localized (confined to primary site) Regional (spread to regional lymphnodes) Distant (cancer has metastasized) Stage Distribution (%) 5-year Relative Survival (%) 68 99.9 25 97.4 4 55.0 Unknown (unstaged) 2 87.5 Stage Distribution and 5-year Relative Survival by Stage at Diagnosis for 2003-2009, All Races, Both Sexes -SEER

What about iodination of salt?

Prevalence of nodular thyroids in percentage Nodular goiter and iodine deficiency Prevalence of Papillary thyroid cancer is higher in areas of iodine repletion: 6.21% in areas of iodine deficiency 16.48% in areas of iodine repletion THYROID Volume 15, Number 2, 2005 Kovacs et al Gray bars: White bars: Nodular thyroids in iodine deficient areas Nodular thyroids in iodine sufficient areas THYROID Volume 15, Number 2, 2005 Kovacs et al

Follicular and anaplastic cancers are more common in iodine depleted areas Papillary thyroid cancer (particularly microscopic PCT) iodine sufficient areas Szpak S et al 2001 Geographic differences in iodine supply in Silesia terrain in relation to cancer risk Wiad Lek 54:169-175

Incidence rate by Race Race/Ethnicity Male Female All Races 6.1 per 100,000 men 18.2 per 100,000 women White 6.6 per 100,000 men 19.4 per 100,000 women Black 3.2 per 100,000 men 10.5 per 100,000 women Asian/Pacific Islander 5.3 per 100,000 men 17.9 per 100,000 women American Indian/ Alaska Native 3.3 per 100,000 men 11.0 per 100,000 women Hispanic 4.4 per 100,000 men 16.4 per 100,000 women

From 2006-2010, the median age at diagnosis for cancer of the thyroid was 50 years of age Incidence (%) Age group 1.8 under 20 15.3 20 and 34 19.9 35 and 44 24.4 45 and 54 19.5 55 and 64 12 65 and 74 5.7 75 and 84 1.4 85+ years Incidence Thyroid cancer AG E Thyroid nodules

United States PCT estimates in 2007: New cases: 33,550 Deaths: 1,530 Common cancer, with a 2.4 fold increase in incidence (3.6 per 100 000 in 1973 to 8.7 per 100 000 in 2002) Vast majority of the increase is in the < 1 cm cancers >50% of cancers diagnosed now are in this size range There is no increase in other forms of cancer 3 : 1 female preponderance

Almost exclusive increase in papillary type No significant change in follicular, MTC, Anaplastic The vast majority are sub 1 cm cancers This raises the question: Increase in diagnosis of subclinical disease Versus Increase in the incidence of cancer

Mortality should drop Improvement in imaging systems Defensive medicine Patient education neck check, radiation exposure etc Better physician training evaluation protocols etc

If increase in detection is the cause increase in small cancers, with drop in the diagnosis of larger cancers In some series, the increase is even though most apparent in small cancers, the larger ones are also on the rise USA 50% are < 1 cm, 30% 1 2 cm and 20% >2 cm Improved detection should lead to increase in all the types of cancers (only apparent in PCT)

Likely a combination of both Regional variations global variation (GB vs Rest of Europe) Influenced by availability of medical care Affluence westernized life-style

Cancer 6 NOV 2014 DOI: 10.1002/cncr.29122 http://onlinelibrary.wiley.com/doi/10.1002/cncr.29122/full#cncr29122-fig-0001

Diagnosis of sub-clinical disease Leads to enormous expense in evaluation and management Also, anguish the family is put through In one study 85 % of patients wanted surgery, even for small cancers at the time of diagnosis

Microcarcinoma frequency is 100 1000 times higher than the incidence of thyroid carcinomas with clinical manifestation The epidemiology of MPCT appears to be different from clinical PCT prevalence 16.48% in areas of sufficient iodine supply Microscopic papillary cancers mortality:? Life time risk of dying from Thyroid cancer 0.06 ( %)

Risk Annual Deaths Lifetime risk Heart disease 652,486 1 in 5 Cancer 553,888 1 in 7 Stroke 150,074 1 in 24 Hospital infections 99,000 1 in 38 Flu 59,664 1 in 63 Car accidents 44,757 1 in 84 Suicide 31,484 1 in 119 Accidental poisoning 19,456 1 in 193 MRSA 19,000 1 in 197 Falls 17,229 1 in 218 Drowning 3,306 1 in 1,134 Bike accident 762 1 in 4,919 Air/space accident 742 1 in 5,051 Excessive cold 620 1 in 6,045 Sun/heat exposure 273 1 in 13,729 Shark attack* 62 1 in 60,453 Lightning 47 1 in 79, 746 Train crash 24 1 in 156,169 Fireworks 11 1 in 340,733 Life time risk of dying from Thyroid cancer 0.06 ( %) New ICD 193 cases:33,550-45,000 Deaths: 1,530-2,000 Source: NY times NSC National Safety Council

Back to our patient and similar patients is there a role for observation?

300 lesions of asymptomatic PTC were followed (Japan) Nonsurgical observation was performed for a mean of 5 (range, 1 17) years OBSERVATION SINCE 1995! 269 (90%) were unchanged 22 (7%) had increased in size 9 (3%) had decreased 3(1%) pts developed apparent lymphnode metastasis 9(4%) of which received surgery after 1 12 yrs of follow-up None developed ET invasion or distant metastasis Sugitani et al World J Surg. 2010 Jan 12.(ahead of print)

Rising incidence of thyroid cancer vs increasing detection particularly the micro PCT The vast majority of sub cm cancers are identified incidentally during imaging performed for other reasons Incidence appears to be higher in iodine replete areas Clinically micro pcts behave more benign than clinical PCTs

It is impractical to biopsy and or remove all incidentally identified tumors Management policy for small cancers Is there a role for conservative approach in USA?