Doctor, Should I be Tested for Cancer, or Not?

Transcription

1 Doctor, Should I be Tested for Cancer, or Not? Verna Mai, MD, FRCPC Community Medicine Cancer Screening CME June 8, 2012

2 Learning Objectives 1. Know the latest 2012 evidence-based guidelines for key cancer sites and why they have changed 2. Understand concepts of the "pro's and con's" of screening 3. Understand how Informed Decision Making and Shared Decision Making interventions can be applied to cancer screening decisions 4. Increased awareness of some tools and resources available to support best practices in screening

3 Conflict of Interest Disclosure Consultant for: N/A Speaker for: Canadian Partnership Against Cancer Received grant/research support from: N/A Received honoraria from: N/A

4 Screening controversy centers on the debate involving two apparently opposing views Cancer screening is good. We all know that cancers are easier to cure when they are found early. So anything we can do to find cancers earlier will save lives. Cancer screening is bad. Most people getting tested will never get the disease in question Even worse, a lot of people end up with extra diagnostic tests, and maybe even unnecessary diagnoses of cancer.

5 Headlines in March,

6 What is Screening? the application of tests, examinations or other procedures which can be applied rapidly to sort out apparently well persons who probably have a disease from those who probably do not. A screening test is not intended to be diagnostic. Persons with positive or suspicious findings must be referred to their physicians for diagnosis and necessary treatment. (adapted from the Commission on Chronic Illness, 1951)

7 Yes, the idea is to find tumours earlier/smaller 7

8 What Benefits Do We Want From Screening for Cancer? Primary outcome we seek is a reduction in the risk of dying from the cancer, because it has been detected early and successfully treated. If finding cancer earlier does not affect the ultimate outcome (death due to cancer) or when it happens, it may be more harmful than beneficial

9 Five year survival can increase with screening even if there is no impact on mortality from screening Then Diagnosed because of symptoms at age 67 Now Five-year survival = 0% Diagnosed because of screening at age 60 X Death at age 70 Five-year survival = 100% X Death at age 70

10 Five year survival increase and an impact on mortality from screening Then Diagnosed because of symptoms at age 67 X Death at age 70 Now Five-year survival = 0% Diagnosed because of screening at age 60 X Death at age 80 Five-year survival = 100%

11 Five year survival 100% for a screen-detected cancer that would not have been diagnosed or caused death ( Overdiagnosis ) Then Cause of death Other than cancer X Death at age 70 Now Diagnosed because of screening at age 60 X Death at age 70 Five-year survival = 100%

12 Rethinking Screening for Breast Cancer and Prostate, Esserman et al. JAMA 2009 After 20 years of breast and prostate screening, we know: Incidence increased and never went to prescreening levels Incidence of regionally spread cancers has not slowed as quickly as the increase in local cancers Welch (JNCI 2010) estimates overdiagnosis as 25% for breast cancer, and 60% for prostate cancer 12

13 A little more emphatically. New thinking on cancer screening October 22, 2009 GINA KOLATA THE HAMILTON SPECTATOR The American Cancer Society, long a staunch defender of most cancer screening, now says the benefits of detecting many cancers, especially breast and prostate, have been overstated. It is quietly working on a message to emphasize that screening for breast and prostate cancer and certain other cancers can come with a real risk of overtreating many small cancers while missing cancers that are deadly. 13

14 Cancers Detected by Screening A. Curable after clinical diagnosis B. Incurable after clinical diagnosis, curable after screen detection C. Incurable after both clinical diagnosis and screen detection D. Cancers not destined to present clinically before death from another cause (overdiagnosis)

15 The Estimated Breast Cancer Mortality Over the Next 10 years For 1,000 Women Based on mortality reduction of one third from regular screening AGE DIE FROM BREAST CANCER WITHOUT MAMMOGRAPHY DIE FROM BREAST CANCER WITH MAMMOGRAPHY AVOID DEATH BECAUSE OF MAMMOGRAPHY Source: Should I Be Tested For Cancer? Maybe Not and Here s Why; H. Gilbert Welch, 2004

16 What s wrong with finding small non-life threatening cancers? In prostate cancer: Many indolent cancers will be identified, biopsies will be done, and surgery or radiation will ensue. Side effects include impotence and incontinence in a significant proportion. Thus, to expose men to this risk, one needs to be certain that the benefits are sufficient to sustain this risk. Active surveillance of men with cancer how acceptable is this to patients? 16

17 Estimate of effects, experienced by men aged (from CPAC anticipatory science.; based on ERSPC trial).) Number Screened Unscreened Number invited Number of positive PSAs 1620 Number of biopsies 1393 Number of potentially aggressive cancers (Gleason >7) Number of low-grade cancers (Gleason score 6 or less)

18 Further estimates of effects Number Screened Not screened Radical prostatectomy Radiotherapy Urinary problems Sexual dysfunction Bowel problems Number of deaths due to prostate cancer

19 Once you have a test that fulfills the principles of screening, and has adequate evidence of benefit, in terms of reducing the risk of dying from the disease with regular screening, then it is important to examine the accuracy of the test to look at how good does this test performs. 19

20 Screening Test Characteristics Test + True Positive - False Negative Disease + - False Positive True Negative Positive Predictive Value Negative Predictive Value Sensitivity Specificity 20

21 McGill researchers move one step closer to breast-cancer blood test By Aaron Derfel, GAZETTE health reporter April 10, 2012 MONTREAL - Scientists at McGill University have crossed a crucial threshold in developing a blood test that could one day detect breast cancer at very early stages and might even render mammography screening obsolete. They sampled the blood of 11 healthy people and 17 patients with breast cancer. They then measured the concentration of 32 proteins. Scientists crossed a key threshold in the search for a better way than mammography to find breast cancer. Using the latest in microarray technology, the researchers found that six of the 32 could be used to establish a signature for the hormone receptorpositive cancer. The findings were published in the April edition of the journal Molecular and Cellular Proteomics.

22 Diagnosis and Screening are Different Diagnosis - Person is often uncomfortable or worried, and so is motivated - Will often be willing to drive long distances and go through discomfort to sort out issues - Risk of side effects of testing and treatment are balanced against higher probability of illness Screening - Person is well, and needs to be persuaded that testing will improve their life - Requires screening to be accessible, and comfortable - Risk of side effects of testing or follow-up important, as are balanced against current health and low probability of illness 22

23 Assessing the Balance of Harms and Benefits Benefits Avoid premature mortality Enhanced treatment options Avoid morbidity Harms Anxiety about the test False positive results False negative results Complications of diagnostic investigations Complications of treatment Unnecessary treatment 23

24 Where Do the Guidelines Come From? U.S. Preventive Services Task Force ( USPSTF) The Task Force makes its recommendations on the basis of explicit criteria intended for use in the primary care setting. Evidence based practice centers ( EPC s) are contracted by the Agency for Healthcare Research and Quality (AHRQ to conduct systematic reviews of the evidence on specific topics in clinical prevention = the scientific basis for USPSTF recommendations. The USPSTF reviews the evidence, estimates the magnitude of benefits/ harms for each preventive service, reaches consensus about the net benefit for each preventive service, and issues a recommendation. Recommendation statements present information about the evidence behind each recommendation, allowing clinicians to make informed decisions about implementation. In Canada, the Canadian Task Force on Preventive Health Care uses a similar approach, and it has started work on guidelines again, after being inactive for the past few years.

25 Rating the Strength of Scientific Research Evidence Agency for Healthcare Research and Quality (AHRQ) Important Categories and Elements for Systems to Grade the Strength of Evidence Quality: the aggregate of quality ra/ngs for individual studies, predicated on the extent to which bias was minimized. Quan<ty: numbers of studies, sample size or power, and magnitude of effect. Consistency: for any given topic, the extent to which similar findings are reported using similar and different study designs

26 Grading Used By the US Preventive Services Task Force (USPSTF) A (strongly recommends) B (recommends) C (no recommendation for or against) D (recommends against) I (insufficient evidence to recommend for or against)

27 U.S. Preventive Services Task Force s Recommendations,2009 Cancer Method Target Population Grade Bladder Urinalysis (microscopy, dipstick), bladder tumor antigen, nuclear matrix protein Adults D Breast Women aged B Mammography (biennial) Women C Breast self-examination D All ages Clinical breast examination I Cervix (as Sexually active women A of 2003; Pap cytology Women > 65 with under adequate screening D review) New technologies and HPV testing Sexually active women I Adults years A Colorectal FOB testing, sigmoidoscopy, colonoscopy Adults years C Adults > 85 years D Computed tomographic colonography and fecal DNA Adults years I Lung Computerized tomography, chest x-ray, sputum cytology Asymptomatic adults I Oral Direct inspection and palpation Adults I Ovarian CA-125, ultrasound, or pelvic examination Adult women D Pancreas Abdominal palpation, ultrasonography, serologic markers Asymptomatic adults D Prostate PSA test, digital rectal examination Men younger than 75 I Men 75 and older D Skin Whole-body skin examination Average risk persons I 27 Testicular Clinical examination Asymptomatic young men D

28 Screening for Prostate Cancer U.S. Preventive Services Task Force, 2008 The USPSTF recommends against PSA-based screening for prostate cancer in men 75 years and older Grade: D recommendation For men younger than 75 the evidence is insufficient to assess the balance of benefits and harms of prostate cancer screening Grade: I statement

29 May 21, 2012 New US Preventive Services Task Force Guidelines

30 Screening for Prostate Cancer U.S. Preventive Services Task Force, May, 2012 The USPSTF recommends against PSA-based screening for prostate cancer Grade: D recommendation Clinical summary: Do not use prostate-specific antigen (PSA)-based screening for prostate cancer. Applies to men in the general population, regardless of age

31 Prostate cancer is a serious health problem that affects thousands of men and their families. But before getting a PSA test, all men deserve to know what the science tells us about PSA screening: there is a very small potential benefit and significant potential harms. We encourage clinicians to consider this evidence and not screen their patients with a PSA test unless the individual being screened understands what is known about PSA screening and makes the personal decision that even a small possibility of benefit outweighs the known risk of harms. USPSTF Co-Chair Michael LeFevre, M.D., M.S.P.H. May 22, 2012

32 prostatecancerscreening.htm

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35 Screening for Lung Cancer U.S. Preventive Services Task Force, 2004 The U.S. Preventive Services Task Force (USPSTF) concludes that the evidence is insufficient to recommend for or against screening asymptomatic persons for lung cancer with either low dose computerized tomography (LDCT), chest x-ray (CXR), sputum cytology, or a combination of these tests. Grade: I Statement. ( Canadian Task Force (2003): D recommendation for CXR; I Statement for LDCT )

36 Lung Cancer Screening new evidence Four major randomized controlled trials (RCTs) have been underway internationally: 1. National Lung Screening Trial, U.S. (LDCT vs.. Chest X-ray)** 2. Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, U.S. (Chest Xray vs no screening) 3. Dutch-Belgian Randomized Lung Cancer Screening Trial, Netherlands and Belgium (LDCT vs. no screening)** 4. Danish Randomized Lung Cancer CT Screening Trial, Denmark (LDCT vs. no screening)** ** high-risk subjects with heavy smoking history of pack years # 2+3 published results in

37 National Lung Screening Trial Research Team. Reduced lung cancer mortality with low-dose computed tomographic screening. NEJM online, June, NLST Key study characteristics Study Population Aged years, men and women 30 pack-years cigarette smoking history; former smokers only if they quit within past 15 years Source of study participants Healthy volunteers meeting the smoking criteria recruited from 33 medical institutions across the U.S. Number of subjects randomized 53,454 ( ) 2 Study Arms 1. Low-dose CT annually for 3 rounds ( 26,722) 2. Single view P-A Chest xray annually for 3 rounds (26,732)

38 National Lung Screening Trial Research Team. Reduced lung cancer mortality with low-dose computed tomographic screening. NEJM, June, NLST Key study characteristics Abnormal screening results: CT: nodules 4mm or greater in diameter/ other suspicious lesions CXR: nodule/mass of any size/ other suspicious lesions Follow-up protocols for abnormal test results Average follow-up period after screening finished T0: CT group 27.3%, CXR group 9.2% T1: CT group 27.9%, CXR group 6.2% T2: CT group 16.8%, CXR group 5.0% ( change in categorization for stable abnormalities at T2) During the 3 rounds, participants with at least one abnormal screening result: CT 39.1%, CXR 16% Diagnostic work-up was determined by the participant s health care provider Followed through to December 31, 2009

39 National Lung Screening Trial Research Team. Reduced lung cancer mortality with low-dose computed tomographic screening. NEJM, June, NLST Key study outcomes Lung cancer specific mortality: 20.0% relative reduction in mortality from low dose CT screening( 95%CI, ; P = 0.004) Mortality from any cause: Low dose CT Arm 247/100,000 person- years CXR Arm 309/100,000 personyears 1877 deaths 1998 deaths 6.7% relative reduction in mortality in the low dose CT group ( 95%CI, ; P=0.02)

40 National Lung Screening Trial Research Team. Reduced lung cancer mortality with low-dose computed tomographic screening. NEJM, June, NLST CXRay screening ( rather than usual care) was chosen as the comparator to low dose CT because CXRay was being evaluated in the PLCO study, at the time NLST was designed. If the PLCO trial were to show a reduction in lung-cancer mortality with CXRay, then a CT vs no screening trial would not be as useful as CXRay would become the standard of care. However, this means that the NLST was not able to compare low dose CT with usual care ( or no screening intervention )

41 Conclusion of the NLST Screening with the use of low-dose CT reduces mortality from lung cancer.

42 Screening by Chest Radiograph and Lung Cancer Mortality: The Prostate, Lung, Colorectal, and Ovarian (PLCO) Randomized Trial Oken, M.M. et al for the PLCO Project Team, Published online October 26, 2011 in JAMA.

43 Screening by Chest Radiograph and Lung Cancer Mortality: The Prostate, Lung, Colorectal, and Ovarian (PLCO) Randomized Trial Oken, M.M. et al for the PLCO Project Team, Published online October 26, 2011 in JAMA. This trial provides good evidence that Chest Xray is not effective for lung cancer screening, when compared to no screening. There was no significant impact on lung cancer mortality in the screening group, as a whole and by different categories of smoking history.

44 National Lung Screening Trial Research Team. Reduced lung cancer mortality with low-dose computed tomographic screening. NEJM, June, NLST Key study outcomes Lung cancer incidence: Rate ratio = 1.13; (95%CI ) Low dose CT Arm CXR Arm 1060 (645/100,000 person-yrs) 941 (572/100,000 person-yrs) As a result of the new evidence published in 2011, the US Preventive Services Task Force is working on new Lung Screening Guidelines to be completed in 2012

45 Screening for Ovarian Cancer U.S. Preventive Services Task Force, 2004 The U.S. Preventive Services Task Force (USPSTF) recommends against routine screening for ovarian cancer. Grade: D Recommendation.

46 Risks and Benefits of Ovarian Screening (CPAC Ovarian Screening Expert Panel, October 2011) Currently, the evidence shows that cancer screening has little impact on ovarian cancer mortality. Additional evidence from the three main randomized trials on mortality outcomes is anticipated over the next few years Evidence has also been accumulating on the potential harms caused by routine screening for ovarian cancer. These harms, including anxiety and repeat testing, result from the follow-up that is required for women who have an abnormal screening result. Besides repeat CA 125 and/or ultrasound testing, such follow-ups may include surgery (laparoscopy or laparotomy) for diagnosis.

47 Current Canadian Task Force on Preventive Health Care Recommendations 2011 The Task Force met in early 2010 to establish topic priorities and guideline development processis underway. Topics being worked on in 2011 are: Screening for breast cancer completed in 2011 Screening for hypertension Screening for depression Screening for diabetes Screening for cervical cancer Screening for obesity Screening for child obesity

48 Canadian Task Force on Preventive Health Care New Recommendations Classification in GRADE

49 And we are not the only influencers Health: The Katie Couric Effect TIME In a study that appears in the current issue of the Archives of Internal Medicine, a team of researchers from Michigan and Iowa reports that colonoscopy rates across the U.S. jumped more than 20% following Couric's examination.

50 And advice is freely given.. Yes, they may produce false positives and some physicians are reluctant to conduct them unless the patient's history indicates he is in a risk group. But if a patient asks for a PSA test then the doctor is almost certain to comply. Just tell your physician your neighbour who is about the same age said he had one and you want one anyway even if the doctor says you face little risk, says Dr.Vesprini. 50

51 Involving patients in decisions about health care (screening) Informed decision making (IDM): Any intervention in communities or healthcare systems intended to promote individuals informed decisions Shared decision making (SDM): A subset of IDM; IDM interventions in clinical settings win which patients and providers express their preferences and participate in decision making

52 Informed Decision-Making Goal: Foster patient s understanding, to enable informed participation in clinical decisions Patients has accurate knowledge, beliefs, and perceptions of risk about the the disease and about the options for screening Patients participate in decision making at the level they desire for the particular decision at hand Facilitation of decision making that is consistent with individual preferences and values Patient feels the decision about screening is right for him/her

53 An SDM approach: Assess Inform/Educate Discuss - Decide Shared decision making ( SDM) take place in clinical settings, involve 1 on 1 interactions between patients and prproviders, mutual information sharing, expressions of preferences

54 Patient-Centered Discussions about Prostate Cancer Screening: A Real-World Approach Gaster B, Edwards K et al. Ann Intern Med. 2010

55 Canadian breast screening decision aid

56 The Estimated Breast Cancer Mortality Over the Next 10 years For 1,000 Women Based on mortality reduction of one third from regular screening AGE DIE FROM BREAST CANCER WITHOUT MAMMOGRAPHY DIE FROM BREAST CANCER WITH MAMMOGRAPHY AVOID DEATH BECAUSE OF MAMMOGRAPHY Source: Should I Be Tested For Cancer? Maybe Not and Here s Why; H. Gilbert Welch, 2004

57 Excerpt from Decision Aid - communicating absolute mortality benefit for women aged If we screen 1,000 women aged years once a year for a period of 10 years: 1 death from breast cancer will be prevented. 12 women will die from some cause other than breast cancer. 2 women will die of breast cancer despite breast cancer screening. How will this affect my chance of dying from breast cancer? Figure 2 - The bar chart shows that death from breast cancer is uncommon. Screening prevents one death from breast cancer among 1,000 women screened each year between ages 40 and 49.

58 Information by Expert Panels, Canadian Partnership Against Cancer at Cancerview.ca under Prevention & Screening

59 The Trouble With Doctor Knows Best By PETER B. BACH, M.D. Published: June 4, 2012 NYTimes Doctors were told last month that we should stop doing so many screenings for prostate cancer with the prostate-specific antigen test. We learned that sigmoidoscopy is a cheaper, easier and effective alternative to colonoscopy for colon cancer screening. And a study I led turned up strong evidence that routine lung cancer screenings are justified only for people at high risk because of heavy smoking in the past. Regular mammograms aren t necessary for women in their 40 s and are needed for women aged only every 2 years. Pap tests for many women are required only every 3 years, not annually. Many doctors will keep doing what they ve been doing all along. Reliance on our instincts and experience like we do for treatments like antibiotics. Testing will catch cancer in some patients the woman in the exam room could be one of them but the difference is that these are well patients getting screening, and we cannot tell how often a test benefits an individual patient or improves her prospects of survival.

60 Should I Be Tested For Cancer? (Welch,H.G) 1. Why are you suggesting the test? 2. Has there been a randomized trial of screening for this cancer? 3. What will we do if my test is positive?

61 In Summary, Screening has become a hot topic, and this will continue, with the many new promising early detection methods Presentation of both potential benefits and potential limitations/harms to patients are becoming a best practice Finding cancers is not enough, finding cancers which will result in a decreased risk of death from cancer is the key Participation in effective screening goes beyond the test itself.. The whole journey after an abnormal screening is equally important.proper diagnostic procedures to get to a diagnosis, followed by effective treatment of cancers detected. Scientific evidence continues to evolve and alter evidence-based screening guidelines: o Which test to use; when to start; what should be the screening interval; when to stop;

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