the thyroid cancer example

Transcription

1 Glass Half Full, Glass Half Empty: Evidence and Perspectives on Over Diagnosis and Cancer Screening the thyroid cancer example Louise Davies, M.D., M.S. Associate Professor of Surgery - Otolaryngology The VA Outcomes Group White River Junction, VT The Dartmouth Institute for Health Policy & Clinical Practice

2 Disclosures Relevant Financial Disclosures Surveillance Epidemiology and End Results Program of National Cancer Institute (inter-agency agreement between VA and NCI) Louise Davies, MD, MS

3 Learning objectives: At the conclusion of this talk, attendees should be able to: 1. Describe the current incidence and mortality trends of the most common type of thyroid cancer. 2. List the main contributors to the increased incidence of thyroid cancer, and explain why these sources are suspected. 3. Describe the consequences of overdiagnosis. 4. Identify one way the problem can be mitigated.

4 The scope of the thyroid cancer problem

5 Data Source Incidence & Survival SEER (Surveillance Epidemiology & End Results) National Cancer Institute maintained Population - based cancer registry: Provides the best US population estimates available Maintained by National Cancer Institute Records diagnosis, pathology results, initial treatment, cause of death 36 years of data ( ) 18 key areas of U.S. contribute data

6 Data Source - Mortality National Death Index Maintained by the Centers for Disease Control Underlying cause of death is coded as cause of death Deaths from all states are obtained Even if you move away from a SEER area after diagnosis, your death is still captured the source for U.S. cancer statistics

7 Rate per 100,000 people Thyroid cancer trends Incidence Year Mortality Current trends in thyroid cancer in the U.S.: Davies, L., Welch, H.G. JAMA Otolaryngology Head & Neck Surgery, in press.

8 Incidence per 100,000 people Incidence trends by histology Papillar y Year Follicular Poorly differentiated Rate: 0.2

9 Rate per 100,000 people Interpreting the trend lines Incidence: all histologies Papillary 3 Mortality Year

10 Interpreting the increase in papillary thyroid cancer Potential explanation 1: There has been a true increase in disease. Treatment advances don t keep pace with incidence Treatment improves faster than disease increases

11 Interpreting the increase in papillary thyroid cancer Potential explanation 2: We are detecting subclinical disease that has always been there. Some proportion of the disease we are now detecting is overdiagnosis

12 Key evidence for the overdiagnosis hypothesis Autopsy studies show sub-clinical papillary cancer is common Harach HR, Franssila KO, Wasenius VM. Occult papillary carcinoma of the thyroid: a normal finding in Finland. Cancer. 1985; 56: Virtually every thyroid had cancer in it Cancer size up to ~1.5 cm. Some cancers invasive Multiple cancers in 28% of glands

13 Trends in thyroid cancer incidence by size Incidence per 100,000 people cm. or less cm > 5 cm Year of diagnosis Incidence rates per 100,000 people in the United States, Data are from the Surveillance, Epidemiology, and End Results Program 9 (SEER), Update of figure from: The Increasing Incidence of Thyroid Cancer in the U.S., Davies, L., Welch, H.G. JAMA 2006; 295(18)

14 Why the 2 cm cutoff for the size analysis? 2 cm. is too small for ½ of experienced clinicians, such as endocrinologists, to feel Wiest PW, Hartshorne MF, Inskip PD, et al. Thyroid ultrasound palpation versus high resolution ultrasonography in the detection of nodules. J. Ultrasound Med. 1998; 17:487-96

15 What about the big cancers? The 12% of the increase due to tumors 2-5 cm The 1% increase due to tumors >5cm? Might the big cancers indicate other potential causes of the increasing incidence?

16 What about the big cancers? It s not just small cancers that get found incidentally: 519 patients from NYU Langone Many large tumors were found incidentally on imaging done for other reasons 29% of tumors 2-4cm 38% of tumors >4cm 39% of patients with positive central lymph nodes Malone et al. Thyroid cancers detected by imaging are not necessarily small or early stage. Thyroid 2013.

17 Radiation exposure Excess risk is definitely present for those under age 20 at exposure. Excess risk persists for at least 50 years. Caveat: 1 big dose all at once what does that mean for the rest of us? Furukawa et al. Long term trend of Thyroid Cancer Risk Among Japanese Atomic Bomb Survivors: 60 Years After Exposure. International Journal of Cancer. 2013

18 Radiation exposure CT scan risk Australian study million people age 0-19 born between 1985 and 2005, followed through Exposure: CT scan at least 1 year prior to cancer diagnosis. Unexposed: no CT scan. 60,674 cancers diagnosed; 3150 in the 680,211 who had a CT scan.

19 Radiation exposure Australian study CT scan increased cancer risk by 24% Every additional CT increased risk 0.16% What does this mean? baseline risk of getting cancer for a newborn is ~1/300 for boys ~1/333 for girls With one CT scan, the risk increases to: ~1.24/300 for boys ~1.24/333 for girls

20 Obesity A large meta analysis confirms association between BMI and thyroid cancer risk Proposed mechanisms: Adipokines: leptin, adiponectin Insulin resistance Increased insulin levels Increased stimulation of thyroid thyroid heperplasia and neoplasia No causal relationship proven Zhao ZG, Guo XG, Ba CX, et al. Overweight, obesity and thyroid cancer risk: a meta-analysis of cohort studies. The Journal of international medical research. 2012;40(6):

21 Other potential contributors Weakly correlative findings, theoretical, no causal pathways demonstrated yet: Iodine excess or insufficiency Dietary nitrates Diabetes Estrogen Autoimmune thyroid disease

22 Summary of the big cancers We find them by accident also Medical imaging before age 20 matters, though it only contributes a tiny amount to the increasing incidence Other potential sources might contribute to the increasing incidence, but are not major causes of the trend

23 Incidence per 100,000 people Conclusion: overdiagnosis is the biggest public health player in the increasing incidence of thyroid cancer 2 cm. or less cm > 5 cm Year of diagnosis Incidence rates per 100,000 people in the United States, Data are from the Surveillance, Epidemiology, and End Results Program 9 (SEER), Update of figure from: The Increasing Incidence of Thyroid Cancer in the U.S., Davies, L., Welch, H.G. JAMA 2006; 295(18)

24 Overdiagnosis Hallmarks of overdiagnosis: small cancers identified the increase is in a cancer type which is known to have a subclinical reservoir mortality has not changed Overdiagnosis is the detection of cancers that would otherwise never become evident in the patient s lifetime. Treatment can only harm these patients because treatment is not necessary

25 Part 2 How does overdiagnosis happen? What are its consequences? What can we do about it?

26 How overdiagnosis happens At level of health care system: Access to care increases likelihood of receiving a thyroid cancer diagnosis

27 County level characteristic Who is most at risk of receiving a thyroid cancer diagnosis? Non-white Uninsured < grade 12 ed. County unemployment English not primary lang. White collar employment Higher family income Correlation coefficient Lower risk Higher risk Thyroid Cancer Incidence and Access to Care. Morris, Sikora, Tosteson, Davies. Thyroid 2013, 23(7):

28 How overdiagnosis happens At level of health care system: Access to care At level of direct health care: Incidental detection of thyroid nodules on tests done for other reasons is common Imaging rates in the U.S. have increased dramatically: CT by 8% and MRI by 10% annually for past 15 years Smith-Bindman R, Miglioretti DL, Johnson E, et al. Use of diagnostic imaging studies and associated radiation exposure for patients enrolled in large integrated health care systems, JAMA. Jun ;307(22):

29 Incidental detection in one study: Radiologic test Chest CT scan Neck ultrasound Neck CT scan Chest x-ray head/neck MRI Myocard. perfusion scan PET scan Intended purpose of the study Cough / chest pain pulmonary embolus evaluation blunt trauma evaluation cancer surveillance carotid or venous evaluation salivary tissue evaluation neck trauma evaluation cancer staging salivary abnormality preoperative (e.g., jt. replacement) shoulder pain evaluation dysmetria cervical radiculopathy optic neuritis multiple sclerosis chest pain cancer surveillance (melanoma)

30 How overdiagnosis happens At level of health care system: Access to care At level of direct health care: Incidental detection At level of pathologist: In the 1980 s pathology reports had just 5 areas to report upon Current guidelines outline 17 aspects of the specimen to comment upon More scrutiny of the thyroids we remove

31 Consequences of overdiagnosis

32 What s the big deal? So we do a few more surgeries

33 The potential scope of the thyroid cancer problem At age 50: 50% have nodules At age 90: 100% have nodules Mortensen, et al. Gross and Microscopic findings of 1,000 clinically normal thyroid glands Journal of Clinical Endocrinology & Metabolism

34 Current treatment practices for thyroid cancer 40,000 30,000 Number of Americans 20,000 19% also had a lymph node dissection No treatment Surgery only Surgery and radiation 10,000 0 Women 31% also had a lymph node dissection Men 19% also had a lymph node dissection 37% also had a lymph node dissection 34

35 Mixing of cancers affects study outcomes Combining incidental with symptomatic cancers falsely improves study outcomes Hypothetical example: New treatment for cancer People with incidentally identified cancers are included in the study The cancer treatment will look more successful that it otherwise would, because those cancers were not clinically aggressive to begin with

36 The consequences of doing more thyroid surgery That person might get a cancer diagnosis heavy psychological burden regular follow ups, with additional anxiety If you take the whole gland they have to take a pill the rest of their lives and get blood tests The risks of surgery are not zero

37 The consequences of doing more Medical bankruptcy thyroid surgery Cancer patients 2.65 times more likely to declare bankruptcy than patients without cancer. Younger patients had risks 2-5 times higher than Medicare age patients Ramsey et al. Washington State Cancer Patients Found to be at Greater Risk for Bankruptcy than People Without a Cancer Diagnosis. Health Affairs 2013, 32(6):

38 How you can help Make sure public health messages are accurate Risks are presented in context Complete information is provided

39 Kills how many? (mortality) What if I get it? What are my chances? (survival) How likely is it that I will get it? (incidence)

40 Thyroid cancer is growing 7 times faster than breast cancer. Ask your doctor to check your neck. It could save your life. Thyroid cancer is growing 5 times faster than testicular cancer. Ask your doctor to check your neck. It could save your life.

41 Pay attention to the sticky parts of cancer epidemiology When you are assessing a message for appropriateness: get all three major data points Cancer Incidence Cancer Mortality Cancer Survival Consider the risks in relation to the other risks people face

42 What do people need to make good decisions? Facts Values Good decisions Courtesy of: Lisa Schwartz, Steve Woloshin, Gil Welch The Dartmouth Institute for Health Policy & Clinical Practice

43 Behind the scenes The VA Outcomes group Gil Welch Lisa Schwartz Steve Woloshin Brenda Sirovich Doug Robertson Robin Larson Jeff Munson Frank Drescher The Dartmouth Institute Anna Tosteson Bill Black Collaborators Luc Morris Cliff Belden Michelle Ouellette Mark Hunter Funding Sources RWJ Physician Faculty Scholars Career Development Award GO Grant pilot award Comparative Effectiveness Research in Cancer Imaging

44 The VA Outcomes Group White River Junction VA Medical Center Geisel School of Medicine Surgery Otolaryngology Head & Neck Surgery The Dartmouth Institute for Health Policy & Clinical Practice