8 ACOFP 55th Annual Convention & Scientific Seminars Cancer Treatment Centers of America: Supercharge Your Knowledge: A Focus on Breast, Cervical and Prostate Screening Guidelines and Controversies Anthony Perre, MD
Cancer Screening guidelines and controversies Anthony Perre MD Chief, Division of Outpatient Medicine, Cancer Treatment Centers of America none Disclosures 1
Objectives Discuss characteristics of an ideal screening test Review current guidelines and data supporting screening for several cancer types in the average risk patient including: Breast cancer Prostate cancer Cervical Cancer Lung cancer Screening test 2
Prevention Characteristics of an Ideal Screening Test 3
Characteristics of an ideal screening Test Characteristics of an Ideal Screening Test What are the metrics to determine effectiveness of a screening test? Relative risk and relative risk reduction Gain in life expectancy Cost per case detected Cost per life saved Gain in quality-adjusted life years (QALYs) Cost of Life years gained (LYG) Number needed to screen (NNS) 4
Total national health expenditures as a percent of Gross Domestic Product, 1970-2016 Cost Out-of-pocket spending Out-of-pocket expenditures have grown steadily since 1970, averaging $1,093 per capita in 2016, up from $119 per capita in 1970 ($590 in 2016 dollars) 5
Life expectancy Breast Cancer Overview Leading Sites of New Cancer Cases & Deaths: 2016 Estimates Percent of Cases by Stage 2% 6% 31% 61% Localized Regional Distant Unknown 12 ACS. Cancer Facts & Figures 2016. http://bit.ly/1shgj3r Breastcancer.org US Breast Cancer Statistics. http://bit.ly/1l92g3w 2017 Rising Tide 6
SCREENING CONTROVERSIES Appropriate age to begin screening? Frequency of mammograms (annual vs biennial)? Age to discontinue screening mammograms? Clinical breast exam (CBE)? Self breast exam (SBE)? Approach in women with increased breast density? 13 2017 Rising Tide Risk Assessment Women who have a personal history of breast cancer, a confirmed or suspected genetic mutation known to increase risk of breast cancer (eg, BRCA1 or BRCA2), or a history of previous radiotherapy to the chest between ages 10 and 30 are at high risk 7
Breast Cancer Risk Assessment Tool https://www.cancer.gov/bcrisktool 15 NCI. Breast Cancer Risk Assessment Tool. 2017 Rising Tide Risk Assessment For women with any family history of breast, ovarian, tubal, or peritoneal cancer, in order to identify those who need a referral for genetic counseling and possible genetic testing for deleterious BRCA1 or BRCA2 gene mutations, and a referral to consider chemoprevention, prophylactic surgery and screening recommendations, the USPSTF recommends one of five simple screening tools: Ontario Family History Risk Assessment Tool Manchester scoring system Referral Screening Tool Pedigree Assessment Tool Family History Screen 2017 Rising Tide 8
Breast Cancer Screening Breast Cancer Screening 9
Breast Cancer Screening < 40 Breast Cancer Deaths Avoided Breast Cancer deaths avoided 40-49Y 50-59Y 60-69Y 70-74Y 3 8 21 13 10
Harms of One-Time Mammography Screening Ages 40 49 y Ages 50 59 y Ages 60 69 y Ages 70 74 y False-positive 1212 932 808 696 mammograms (false alarms) Breast biopsies 164 159 165 175 False-negative mammograms (missed cancers) 10 11 12 15 Benefits vs. Harms Variable Ages 40 74 y Ages 50 74 y Fewer breast cancer deaths 8 (5 10) 7 (4 9) Life-years gained 152 (99 195) 122 (75 154) False-positive tests 1529 (1100 1976) 953 (830 1325) Unnecessary breast biopsies 213 (153 276) 146 (121 205) Overdiagnosed breast tumors 21 (12 38) 19 (11 34) 11
Annual vs. Biennial Variable Ages 50 74 y, Annual Ages 50 74 y, Biennial Screening Screening Fewer breast cancer deaths 9 (5 10) 7 (4 9) Life-years gained 145 (104 180) 122 (75 154) False-positive tests 1798 (1706 2445) 953 (830 1325) Unnecessary breast biopsies 228 (219 317) 146 (121 205) Over diagnosed breast tumors 25 (12 68) 19 (11 34) False-positive test result, % False Positives Start at Age 40 y Annual Screening Biennial Screening 61.3 41.6 (59.4 (40.6 63.1) 42.5) Annual Screening 61.3 (58.0 64.7) Start at Age 50 y Biennial Screening 42.0 (40.4 43.7) False-positive biopsy recommendation, % 7.0 (6.1 7.8) 4.8 (4.4 5.2) 9.4 (7.4 11.5) 6.4 (5.6 7.2) 12
Breast Cancer Screening GROUP FREQUENCY 40-49 50-69 >70 USPSTF (2016) Q2 Y DISCUSSION YES YES, TO 74 CANADIAN TF Q2-3 RECOMMEND AGAINST YES YES, TO 74 UK NHS Q3 YES, START AT 47 YES YES, TO 73 ROYAL AUSTRALIAN COLLEGE OF GENERAL PRACTITIONERS Q2 NO YES NO ACOG Q1-2 DISCUSSION YES YES, AT LEAST UNTIL 75 ACP Q1-2 DISCUSSION YES YES, TO 74 AAFP Q2 DISCUSSION YES YES, TO 74 ACS Q1 45-55,THEN Q2 START AT 45 YES YES, LIFE EXPECTANCY > 10Y ACR Q1 YES YES YES,INDIVIDUALIZE NCCN Q1 YES YES YES SBE ACS USPSTF ACOG NO NO NO* 13
CBE ACOG NCCN ACS Yes - C Insufficient evidence NO Breast Density 14
Breast Density Screening options - Film vs. Digital Digital breast tomosynthesis (DBT) Hand-held ultrasound vs. automated ultrasound MRI ASTOUND STUDY 15
Breast density Barriers to implement screening US: Impractical to expect radiologist to perform screening as in ACRIN study Lack of standardized training for technologist in the USA Increased out of pocket cost for patients DBT much easier to implement Cost/Benefit 16
Cost/Benefit Cost/Benefit 17
Cost/Benefit Leading Sites of New Cancer Cases and Deaths: 2016 Estimates 36 ACS. Cancer Facts & Figures 2016. http://bit.ly/1shgj3r 2017 Rising Tide 18
Identifying High Risk Patients African American Family history Patients with one or more first-degree relative diagnosed with prostate cancer earlier than age 65 Inherited gene mutations BRCA1 and BRCA2 Lynch Syndrome 37 2017 Rising Tide Digital Rectal Examination (DRE) No controlled studies have shown a reduction in the morbidity or mortality of prostate cancer when detected by DRE at any age Most cancers detected by DRE are advanced Studies have estimated that PSA elevations can precede clinical disease by 5-10 years 19
Prostate-specific Antigen (PSA) Prostate Cancer Screening PSA Velocity Free PSA [-2]ProPSA Intact PSA Kallikrein related peptidase 2 Pca 3 20
Prostate Cancer screening PSA or no PSA? May 2012: USPSTF recommends AGAINST prostate-specific antigen (PSA)-based screening for prostate cancer (D) 2017 USPSTF - The USPSTF recommends that clinicians inform men ages 55 to 69 years about the potential benefits and harms of prostatespecific antigen (PSA) based screening for prostate cancer. (C) 42 USPSTF. http://bit.ly/2hws9gi 2017 Rising Tide 21
Prostate Cancer Screening Based on 2 large studies European Randomized Study of Screening for Prostate Cancer (ERSPC) Prostate, Lung, Colorectal and Ovarian Screening Trial (PLCO) AHRQ rated as fair quality ERSPC 22
Prostate Cancer PLCO 23
Goteborg What changed? USPSTF Additional follow up showed a reduction in mortality (1 man per 1000 screened) after follow up of 13 years. Also harms may have been mitigated by active surveillance 24
American Urologic Association The AUA recommends that beginning at age 55 and to age 69, men engage in shared decisionmaking with their doctors about whether to undergo PSA screening. The AUA doesn t recommend routine PSA screening for men over age 70, or for any man with less than a 10- to 15-year life expectancy 49 American Urologic Association PSA Screening in men under the age of 40 is not recommended. Routine screening for men between 40-54 years old AT AVERAGE RISK is not recommended. Screening intervals of two years vs. one year are preferred. PSA screening is NOT recommended for men over the age of 70 with less than a 10-15 year life expectancy. 50 25
American Cancer Society (ACS) The ACS recommends that men consult with their doctors to make a decision about PSA testing. According to the ACS, men should explore the risks and benefits of the PSA test starting at age 50 if they are at average risk of prostate cancer and have at least a 10-year life expectancy, at age 45 if they are at high risk and at age 40 if they are at very high risk (those with several firstdegree relatives who had prostate cancer at an early age). Prostate Cancer Screening Key questions Does the effectiveness of PSA-based screening vary by subpopulation/risk factor (e.g., age, race/ethnicity, family history, and clinical risk assessment)? 26
COST? The incremental cost per quality-adjusted lifeyear (QALY) for PSA screening was A$147,528. However, for years of life gained (LYGs), PSAbased screening (A$45,890/LYG) appeared more favorable. Optimized AS (active surveillance)improved cost utility to A$45,881/QALY Cervical Cancer 27
Human Papillomavirus 1. http://www.cdc.gov/std/hpv/stdfact-hpv.htm; accessed 1/13/2015 2. Munoz et al. (2003). NEJM 3. The World Health Report 1999: Chapter 5 and Statistical Annex and CDC Small, non-enveloped DNA viruses that infects only stratified epithelial tissues Over 140 have been identified in humans, only 40 are known to infect the oral and anogenital tract and a small subset of these have been linked to cervical cancer 79 million Americans are currently infected with HPV and 14 million new cases occur each year 1 Most common sexually transmitted virus in the U.S. HPV infection is the most important risk factor for cervical cancer Odds ratio of cervical cancer if HPV16+ versus HPV- is 435 2 Odds ratio of lung cancer in male smokers versus non smokers is 8 3 Cervical Cancer 28
How well does cytology based screening perform? Cause, n (%) Kaiser study(1) Swedish study(2) No recent screen 464 (56%) 789 (64%) Cytology detection failure 263 (32%) 300 (24%) Failure of follow-up of abnormal cytology 106 (13%) 91 (7%) 1. Leyden WA, et al. J Natl Cancer Inst 2005; 97:675 683; 2. Andrae B, et al. J Natl Cancer Inst 2008; 100:622 629. ICC, invasive cervical carcinoma. What is wrong with cytology alone? Cytology has low sensitivity ( FN) for detecting CIN2 or worse 1 Cytology is less effective in detecting AIS and adenocarcinoma 2 Highly variable cytology results between cytopathologists and between laboratories 3 29
Sensitivity* for CIN2 (%) 3/14/2018 Results from two rounds of HPV DNA testing versus cytology screening: Italian study = 94,000 women screened twice 3 years apart HPV arm Cytology arm When found CIN3 Cancer CIN3 Cancer Round one 98 7 47 9 Round two 8 0 17 9 In total 106 7 64 18 WITH HPV TESTING, CIN3/cancer found sooner Ronco G, et al. Lancet Oncol 2010; 11:249 257. Italian women aged 25 60 at recruitment. Cytology has low sensitivity for detecting CIN2 or worse 100 Sensitivity of cytology vs. HPV DNA for CIN2 80 60 Average increase 35.7% 40 20 Cytology HPV DNA Test 0 Bigras (N=13,842) Cardenas (N=1,850) Coste (N=3,080) Kulasingam (N=774) Mayrand (N=9,977) Petry (N=7,908) Whitlock EP, et al. Ann Intern Med. 2011; 155:687 697, W214 5. Studies performed in developed countries in women 30 years and older. 30
Cumulative detection rate of cervical cancer (10 6 ) 3/14/2018 Low sensitivity of pap results in decreased protection from getting cervical cancer compared to HPV screening 100 90 80 70 60 2013 review of 4 trials, >176,000 women: 1. The reduction in cancer is 70% greater for women in HPV testing arms 2. The trust in the negative result lasts longer Pap 50 40 30 20 10 0 70% 0 2 4 6 8 Time since negative test at entry (Years) HPV Ronco G et al. Lancet. 2013. www.thelancet.com Published online 11/03/13 http://dx.doi.org/10.1016/s0140-6736(13)62218-7 Cervical Cancer Screening 31
Screening option #1 Cytology screening Women 21-29: Recommended screening method* Women 30 and above an option Rescreen 3 yrs Pap- HPV- Rescreen 3 yrs Pap ASC-US HPV Test >ASC-US Colposcopy HPV+ Colposcopy *Per 2011 ACS, ASCCP, ASCP screening guidelines and ACOG Practice Bulletin 1,2 Management strategy may be different for women 21-24 years of age 3 1. Saslow et al. (2012). AJCP 2. ACOG practice bulletin 131 (2012) 3. Massad et al. (2013). JLGTD Screening option #2 HPV & Pap co-testing Women 30-65: Preferred screening option* NILM/HPV- ASC-US/HPV- Rescreen 5 yrs Rescreen 1 yr Pap HPV Test NILM/HPV+ OR HPV16/18 HPV16/18- Rescreen 1 yr HPV16/18+ Colposcopy ASC-US/HPV+ >ASC-US Colposcopy *Per 2011 ACS, ASCCP, ASCP screening guidelines and ACOG Practice Bulletin 1,2 ASC-US/HPV-: co-test at 3 years 3 LSIL/HPV-: repeat co-testing at 1 year is preferred 3 1. Saslow et al. (2012). AJCP 2. ACOG practice bulletin 131 (2012) 3. Massad et al. (2013). JLGTD 32
Screening option #3 Primary HPV screening Women 25 years of age (ASCCP ALGORITHM) HPV- Rescreen 3 yrs cobas HPV Test HPV16/18 12 other hrhpv+ Pap NILM Rescreen 1 yr ASC-US Colposcopy HPV16/18+ Colposcopy Alternative option to current cytology-based screening methods per SGO/ASCCP Interim clinical guidance ASCCP Algorithms (2015) Cost QALY 15-35,000 dollars depending on method 33
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