The Debate: Is screening s effect on mortality significant? Cancer incidence/death/ gender US

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2 WHAT IS CANCER? 1) A neoplastic Dz with a fatal natural outcome. 2) A cellular abnormality. which grows rapidly causing death. 3).. which grows slowly. 4). which stops growing. 5). which regresses. -Welch H G, Black W JCNI 2010 An Effective Screening test for Cancer must : Be accurate, easy to of administer, acceptable Detect clinically important CA at a pre-clinic stage Asymptomatic! Rx at pre-clinical stage leads in better outcomes than Rx at clinical stage -Hoffman, R NEJM 2011;365: The Debate: Is screening s effect on mortality significant? Screening the detection of indolent CAs. Cannot distinguish CAs that pose minimal risk from those posing substantial risk. Overdetection/over treatment of non-life threatening CAs. Cancer incidence/death/ gender US What is most common Ca in females? What is most common Ca in males? What is most common in females and males? What Ca is leading cause of death in F + M? Possible answers: a) breast b) lung c) colon d) prostate e)uterus f) liver g) melanoma h) brain Incidence/Death rate from most Common Cancers US 2015-ACS New cases Men Women Prostate 181 K Breast 247 K Lung 118 K Lung 106 K Colo-rectal 71 K Colo-rectal 64 K All sites 841K 844 K Deaths Lung 86 K Lung 72 K Prostate 36.1K Breast 40 K C-R 26.0K C-R 23 K All sites 314K 281 K -CA Cancer J. Clin 2016: 66;1-70. What is Cancer overdiagnosis? A term used when detected cancer would not go on to cause symptoms or death because - the cancer never progressed or was at very early stage -Patient had competing risk for mortality and died of something else -Welch HG, JNCI 2010;102:

3 Conundrum with Overdiagnosis Clinician can never know if it is the correct diagnosis or OD at time of diagnosis. Currently, we normally Rx all; although patients cannot benefit from unnecessary Rx, they can be. What about Primum no nocere or to abstain from doing harm? Just aphorisms? Prerequisites for overdiagnosis Existence of Disease Reservoir which has a substantial number of detectable subclinical cancers. - Prostate: 30-70% in men >60 yrs - Breast: 7-39% in middle aged woman y/ o - Thyroid: % - depends on how thin a slice - Variability depends on pathologists, and threshold for labeling it as CA -Welch HG, JNCI 2010;102: Welch HG, JNCI 2010 Disease Reservoir, Risk of Death/Mets and %Over Diagnosed % Impact of Overdiagnosis % Ca %Death/Mets OD % Prostate Men > Thyroid Adults yrs old Breast Women (40-70 yrs ) Welch HG, JNCI Leads to unneeded Rx with risk 2. False + - transitory impact. 3. O.D life-long: impacts sense of well-being, obtaining insurance, (ACA) - physical health, longevity Welch GH, Black WC -JNCI O.D Addressing the Problem No right answer -- involves a trade-off of avoidance of death from Ca vs. O.D -Balance between risks and harms -What is the role of a primary care clinician? -Mature discussion and joint decision - Primum no docere to do no harm - Welch GH, Black WC -JNCI Benefits vs. Risks screening MG in 50 y/o Female Screen y/o female annually x 10 yrs. Benefits Risks 1 woman avoids BC death 2-10 will be OD and Rx needlessly 5-15 told they have BC that would otherwise not effect prognosis will have at least 1 false alarm ( Bx) - Welch GH, Black WC -JNCI

4 Screening, Incidence and Mortality 1. Breast/Prostate/?Lung incidence rates with screening but not much mortality--adjuvant Rx 2. Colon/Cervical - incidence and mortality (slow growing but consequential) 3. Thyroid/Melanoma indolent tumors but no impact on aggressive? No decrease mortality - Esserman, L JAMA 2013 How should we inform our patients about the Path report Is it Cancer or IDLE? What is our ultimate responsibility? - Reserve cancer for lesions with reasonable likelihood of lethal progression if no Rx - Label Pre malignant conditions (ductal Ca in situ or high grade Prostate - Intraepithelial neoplasia) as IDLE :indolent lesions of epithelial origin Esserman, L JAMA: Aug 2013 Breast Cancer The Changing Burden of Disease 2013 v K new case 2013; 247 K K deaths / 2013 v. 40 K 2015 Most Common Ca in Woman and 2 nd leading cause Ca mortality -CA: A Ca J for Clin.2013:63;11-12 CA: A Can. J Clin. 2016: 66:1-70 USPSTF Final Recommendations Breast Cancer: Screening 2016 Risk factors that may influence when to commence screening: Advancing age is most important risk factor for most women Having 1st degree relative associated with 2 fold increase BC in women age putting them in same risk pool as age Many other risk factors have been associated with BC but most are too weak or inconsistent and would not likely influence decision Burden of Disease 125 new cases of BC and 22 deaths/yr./100,000 US women Mean age of diagnosis remains unchanged at 64 since late 1970 s Median age of death is 68 years (Median is the middle value in a series of values arranged from smallest to largest. Risk Factors: Additional Considerations 5-10% of women who develop BC have a mother or sister with BC Women with a BRAC1 or BRAC2 gene mutation have 4 X higher risk Although NHW woman have had >incidence rates than African Am. Women those rates now converging; however mortality rates remain higher 31 v ,000 women/yr. Reasons not clear; AA have more aggressive and treatment resistant forms and triple neg. phenotypes. Earlier screening would not impact this. Other major factors are SES differences and health system failures. - Accessed March Historical Recommendations Breast CA. Screening Aged Recommend starting mammography at age 40: Q 1-2 yrs American Cancer Society (2003) Canadian Task Force on Preventive Care (2001) ACOG (2003) Begin age 50 ACP (2007) WHO (2009) Trends in Breast Ca Incidence and Mortality Breast cancer mortality has been decreasing by 2.3%/yr overall; 3.3%/yr for women aged years since 1990 Attributed to MG screening and Rx advances BC incidence decreased 6.7% in 2003 compared to 2002 (stopping HT)

5 Background on the Mammography Controversy Clinical trial data are flawed; trials used now-outdated technology Mammography for women between age 40 and 49 y is highly controversial Mammography in women >69 yrs has not been adequately studied USPSTF Recommendation 2009 USPSTF recommends AGAINST routine screening MG in women aged years The decision to start BIENNIAL screening MG is an INDIVIDUAL ONE based on patient context, and the patient s values regarding specific benefits and harms Recommendation: There is moderate or high certainty the benefit is small Then Change in Recommendations for Women Aged years--what changed? Why change to biennial screening? Benefits: USPSTF finds CONVINCING Evidence that screening with film mammography REDUCES BC mortality for women aged yrs There is a greater absolute risk reduction for women aged yrs; strongest age Decision analysis performed for projected that biennial screening (Q 2 y) produced 70-99% of benefit of Q 1 yr., with reduction in harms associated with false + screening Summary USPSTF finds Convincing Evidence that MG between ages years reduces BC mortality Recommends Against screening because small benefit outweighed by harms. Woman may not agree that the harms > stated benefit Individualizing may result in less women of color, poor women getting MGs compared to other women What does this mean if you are a 40 something female? You should talk to your doctor and make an informed decision about whether MG is right for you based on your family history, general health, and personal values. Diana Petitti, MD, MPH Vice Chair, U.S. Preventive Services Task Force November 19, 2009

6 Ductal Carcinoma in Situ D.C.I.S 4,600 cases 1982; 64, 000 cases 2008 Earliest stage of BC; lesion size of grain/salt 30 yrs of confusion, difference in opinion, under and overtreatment 90% curable ; only 30% become invasive yet Rx is surgery/rads/drugs (similar to indolent prostate ca) 2008 Susan Komen study 90,000 c DCIS either did not have Ca or received wrong therapy Prostate CA in US Burden of Disease K cases /y K in Prevalence 1 in 6 men/lifetime - 30 K deaths 2013; 26 K in Median age of death from Prostate CA is 80 yrs.; 71% of deaths >75 yrs. - African-Amer. have higher incidence compared to white men (217 vs. 134/100,000) -NY Times July 19, 2010 Stephanie Saul -CA A Cancer J Clin. 2013;63: CA A Cancer J Clin 2016; 66:1-70 How Common is Prostate CA? 100 Men in this room- Random sample 17 of us will end up with Prostate Ca 3 of us will die from it We don t know which of us! Autopsy 50 y/o men-- 30% have it Autopsy 70 y/o men 70 % have it Prostate CA Screening 2012 Benefits vs. Harms PSA has False + secondary to infection, ejaculation, BPH, instrumentation Prostate Biopsy painful; can lead to infection, bleeding Rx associated with significant urinary & bowel incontinence and impotence -NY Times Sunday Magazine Hoffman, R NEJM 2011;365: CA: A Cancer J Clin Jan/Feb 2012 The Changing Minds of Experts Prostate Screening 2008 and 2011 USPSTF 2011 Update Changed to Grade D Do not screen as Harms>Benefits Amer. Cancer Society Historically, PSA+DRE for all men beginning age 50 or (45 high risk) In 2010 changed; If have a 10 year expectancy patient screening should NOT sans an informed decision, patient request. Same in 2016; to be revisited Ca A Ca J for Clin. 2016;66: Amer Cancer Society + PSA Resulted in substantial over-dx and Rx Clear evidence of early detection: no evidence saved lives Prostate Ca mortality declining in US as well as countries w/o PSA Every Rx looks good when 90% of men getting do not need it Adopting Rx and technologies sans adequate assessment is MEDICAL GLUTTONY -Otis Brawley MD CEO ACS

7 POTENTIAL HARMS of Rx with SURGERY / RADIOTHERAPY for Prostate Cancer I need to know the odds Doc Give me some numbers The estimated harms included incontinence and erectile dysfunction in 200 to 300 of 1000 men treated with surgery or radiotherapy AND Death in 5 men within one month of prostate CA surgery Primum non nocere Principle of Non Maleficence 96 --CA: Cancer J for Clin 2013;63:95- National Lung Screening Trial Update Two recent publications! Persons with 30 pack yr and age in study Yearly low density (LD) CT Reduced mortality by 20% NEJM Aug Lung Ca Screening Insurance Benefit Lung Ca screening would save thousands at relatively low costs Health Affairs April 2012 Lung Ca Screening Modalities CXR does not extend life too late when visible. National Lung Ca Screening Trial (NLST) NIH funded - Screened high risk with low dose CT (LDCT) For every 5 high risk pts screened Q 1 yr., ONE person prevented from dying of lung Ca Harms: some false + which means more tests; some false- WHO Should BE SCREENED 2016? Age: Hx: Current or former smoker; 30 pack yrs. If active refer to smoking cessation Former Smokers: If quit <15 yrs. ago General Health: No metallic implants or devices; No home oxygen or poor general health Ca: Cancer J Clin. 2013:68: Ca: Cancer J Clin. 2016:66: Key References 1. Warner, E. Breast Cancer Screening NEJM 2011;365: Smith, RA, Andrews K, Wender R. Cancer Screening in the U.S A Review of Current ACS guidelines and Current Issues /CA :Cancer J Clin 2016;66 (2): Screening for Colorectal Cancer: A Statement from the American College of Physicians. Ann Intern Med 2012;156: Penson, DF. The Pendulum of Prostate Cancer Screening. J Amer. Med Assoc. 2015;314 (9): NEJM. 2. AHRQ. The Guide to Clinical Preventive Services March 10, 2016 This is US Preventive Services Task Force