This document discusses the rising rates of thyroid cancer diagnosis and treatment in the United States, and strategies to address the issue of potential over-diagnosis and over-treatment. It notes that while new thyroid cancer cases have tripled in recent decades, mortality rates have remained stable, suggesting many of these additional diagnoses are indolent cancers that do not require aggressive treatment. The document advocates for more conservative surgical management and observation for small, low-risk cancers. It also proposes renaming some indolent cancers and limiting unnecessary imaging to help reduce over-treatment. While these approaches could help address the problem of over-diagnosis, challenges remain in differentiating cancers requiring treatment from those that can be safely observed.

1. Lawrence Andrew “Drew” Shirley
October 14th, 2016
Surgical (or Non-Surgical)
Management of Thyroid Cancer in the
Era of “Over-Diagnosis”

2. The Problem of Thyroid
Cancer in the 21st Century
2

3. The Rise of Thyroid Cancer
New Cases of
Differentiated
Thyroid Cancer in
the US:
2009 = 37,200
2014 = 63,000

4. The Future of Thyroid Cancer
4
Lubitz, et al. Cancer. 2014 May 1;120(9):1345-52
Rahib L, et al. Cancer Res. 2014 74:2913-21.

5. The Outcomes of Thyroid Cancer
5

6. The Cost of Thyroid Cancer
 Estimated Cost of Care in 2013 in the US
 $1.6 BILLION
 Projected Cost in 2030
 $3.5 BILLION
6
 2.5 x more likely to file
for bankruptcy than
those without cancer
(highest incidence rate
for any cancer)
Lubitz et al. Cancer. 2014 May 1;120(9):1345-52
Ramsey et al. Health Affairs. 2013 6:1143-52.

7. Summary of The Problem
 Increasing Incidence
 Increasing Costs
 Stable, Excellent Outcomes
 OVER-TREATMENT
7

8. How to Slow Over-Treatment of
Differentiated Thyroid Cancer
 Watch It
 Rename It
 Stop Looking for It
8

9. Watch It
(Extent of Surgery)
9

10. Sosa, et al. 2014 National Cancer Database
Review
 PTC 1-4cm
 1998-2006
 54,926 total thyroidectomies
 6849 lobectomies
 Assessed for differences in overall survival
10

11. No Significant Difference in Survival
11

12. Wang, et al. 2014 Papillary Thyroid
Microcarcinoma Treatment
 Review of 29,512 patients with PTCs <1cm in SEER
 73.4% had total thyroidectomy
 Radioactive Iodine given to 31.3%
 No sig diff in DSS for extent of surgery
 5 and 10 y DSS 99.6, 99.3%
12

13. Survival of Patients with microPTC Similar to
General Population
13

14. 2015 ATA Guidelines - Let’s Take it Down a
Notch
14
 For Low-risk Differentiated Thyroid Cancers 1-4cm
 “Initial surgical procedure can be either a bilateral
procedure (near total or total thyroidectomy) or a
unilateral procedure (lobectomy)”
 For Microcarcinomas (<1cm)
 “If surgery is chosen”, lobectomy alone is sufficient

15. Ito et al. 2010 – Observation Trial
 1395 pts with microPTC (<1cm)
 340 observation
 1055 immediate surgery
 Mean observation period 74 months
 109 (32%) observed -> surgery
15

16. Ito, et al. – 5 and 10 Year Data
 At 10 years, 15.9% tumor grew >3mm and 3.4% with
new LN mets
16
% Tumor Enlargement % Developed Lymph Node Mets

17. Concurrent Observation Studies
 Sugitani et al, 2010, Japan
 230 patients
 5 year
 4.6% tumor growth, 1.5% LN mets
 15.5% surgery
 Pace et al, 2013 - Memorial Sloan Kettering Group
 Ongoing
 71 patients
 15 months – 1.4% tumor growth and 1.4% LN mets
 8.5% surgery
17

18. When Papillary Microcarcinomas are Still
Dangerous…
 Clinical presentation, especially vocal cord paralysis
 Present with clinically apparent lymphadenopathy
 Present with distant mets (very rare)
 Present with tall cell variant or poorly differentiated
on FNA (very rare as well)
18

19. Patients and the “C” Word
19

20. WAR!
20

21. Rename It
21

22. Patient’s Perception of Thyroid Cancer vs.
Reality
 279 Patients with thyroid cancer given QoL questionnaire 15
years after diagnosis
 19 (7%) had recurrence
 134 (48%) had concerns about recurrence
 Those with concerns has lower HRQoL in 5 areas
22
Hedman et al, Acta Oncol 2015

23. Thyroid Nodules in the Mainstream Media
23

24. How Common is EFVPTC?
 Encapsulated follicular variant of papillary thyroid
cancer
 Incidence increased 2-3 fold over 2-3 decades
 Currently, 10-20% of all thyroid cancers
24

25. Nikiforov, et al. 2016
 24 pathologists reviewed specimens from 109
patients with noninvasive encapsulated follicular
variant of papillary thyroid cancer (EFVPTC)
 Also 101 with invasive EFVPTC
 Assessed for outcomes
25
Nikiforov et al, JAMA Oncology 2016

26. No Adverse Events for Noninvasive
EFVPTC
26
Nikiforov et al, JAMA Oncology 2016

27. No More “Cancer”
 Noninvasive encapsulated follicular variant papillary
thyroid cancer has now become…
 Noninvasive follicular thyroid neoplasm with
papillary-like nuclear features or…
 NIFT-P
27

28. Renaming MicroPTCs?
 5-10% Adults
 Per Mayo Group (Brito, et al), for cancers:
 <2cm
 No family history
 No radiation exposure
 They should now be called…
 Micropapillary lesions of indolent course, or…
 MicroPLICs
28
Brito et al, 2014 Future Oncol. 2014 10:1-4

29. Stop Looking For It
29

30. The Prevalence of Thyroid Pathology
 Thyroid nodules
 Physical Exam – 4-7%
 Imaging – 30-67%
 Autopsy study (1955) – 50% had nodules
 Up to 20% of excised nodules cancer
 Thyroid Cancer
 Autopsy study (1985) – ~ 33% with thyroid cancer
 2-3mm cuts – if 1mm cuts, could approach 50%
30
Mortensen 1955 JCEM
Harach et al, 1985 Cancer 56:531-8

31. “Over-Diagnosis”
31

32. Diagnostic Tools vs. Incidence
32

33. Davies and Welch, 2014
 Reviewed SEER data from 1975 – 2009
 Incidence tripled 4.9 -> 14.3/100,000
 PTC 3.5 -> 12.5/100,000
 Mortality stable at 0.5/100,000
 Increased incidence -> increased imaging
33

34. Exposure to Medical Care
 Per Davies and Welch, 3 clinical pathways to
address:
 Opportunistic Screening
 Diagnostic Cascade
 Serendipitous Detection
 “Physicians’ thresholds to palpate, image, and
biopsy the thyroid have likely fallen too far.”
 “Clinicians…need to be asking themselves whether
they are looking too hard for thyroid cancer.”
34

35. Critics of Davies/Welch Conclusions
 “Had it covered just the last 10 years, critics say, it
would show that the death rate from thyroid disease
is increasing faster than any other cancer except
liver cancer.”
 Large tumor incidence
 Incidence in poorer countries
35

36. Effect of U/S Screening in South Korea
 In 1999, Korean physicians began offering routine
cancer screenings, including neck U/S
36

37. Decreased Screening and Thyroidectomy
Rates
37

38. Mayo Clinic Cohort
 Rochester Epidemiology Project
 Patient Cohort from 1935
 Evaluate How Diagnosed
38

39. Mayo Group – Incidence vs Mortality
39

40. Trends in Mayo Cohort – More Low Risk
PTC
40

41. Mayo Group – How Diagnosed
41

42. 42 Vaccarella S et al. N Engl J Med 2016;375:614-617.
Observed versus Expected Changes in Incidence of
Thyroid Cancer in 12 Countries
• Approximate # of patients “overdiagnosed”
from 1988-2007 per study:
• US - 228,000
• Italy – 65,000
• France – 46,000
• Japan – 36,000
• South Korean women (1993-2007) -
77,000
• Thyroid cancer cases in women due to
“overdiagnosis”:
• South Korea - 90%
• US, Italy, France, and Australia - 70
to 80%
• Japan, the Nordic countries, and
England and Scotland - 50%
• Overall, estimate 470,000 women and
90,000 men “overdiagnosed”
• “Steady incremental increases over time
and little evidence of stabilization.”

43. New York Times on “Overdiagnosis”
43

44. Some Choice Quotes from the NYT Article
 70-80 % of women “who were told they had thyroid
cancer…actually had tumors that should have been left
alone”.
 “led doctors to actively look for such minuscule lumps by
screening healthy people”
 “Once doctors find a tiny nodule, removing the thyroid is
often the remedy”
 “Some thyroid cancers, of course, really are dangerous, but
they tend to be larger than the tiny ones found with
scans.”
 “But a rise in cancer cases while the death rate does not
budge points to overdiagnosis.”
 “And that, sadly enough, is what has happened”.
44

45. Is Incidence Plateauing?
 Update of SEER Data
 From 2010-2012, incidence stabilized
 Attributed to more measured work-up and
treatment
45
Morris, Tuttle, Davies. JAMA Otolaryngol Head Neck Surg. 2016 Jul 1;142(7):709-11.

46. The Problem with the Solutions
 Many patients will not accept “observation”
 Renaming small cancers will not completely fix, as
small cancers can still metastasize
 Avoiding imaging and further work-up of these
nodules can miss the opportunity to catch these
cancers before they spread
 “Progress, but no precision”
46

47. Next Steps
47

48. Separating Out the Bad Actors
 Imaging
 PET scan/other metabolic imaging
 Molecular testing
 Afirma and Thyroseq (but for cancers specifically)
 BRAF/RAS/TERT promoter mutations
 Other biomarkers…
48

49. Conclusions
 Thyroid cancer is increasing in incidence, on track to be 4th most
common cancer by 2030
 Majority of this increase in cancer incidence is due to small papillary
thyroid cancers, but they are still treated aggressively
 2015 ATA guidelines recommend more measured approach to work-
up and surgical treatment (lobectomy, possibly observation)
 Observation trials show slow rate of tumor growth and lymph node
metastases – but not ZERO
 Re-naming more indolent thyroid nodules to remove the word
“cancer” may stem aggressive treatment (NEFVPTC -> NIFT-P)
 Some groups advocate lessening imaging and biopsies of thyroid
abnormalities to “decrease” cancer rates and treatment
 Need biomarkers to determine which cancers will spread and which
will remain indolent
49

50. Acknowledgements
 Department of Surgery:
 Timothy Pawlik
 Steven Steinberg
 Raphael Pollock
 John Phay
 Shirley Lab:
 Sam McCarty
 Ringel Lab:
 Matthew Ringel
 Moto Saji
 Department of Pathology:
 Ben Swanson
50

51. Questions?
51