Updates In Cancer Screening: Navigating a Changing Landscape

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Updates In Cancer Screening: Navigating a Changing Landscape Niharika Dixit, MD I have no conflict of interest. 1

Why Should You Care Trends in Cancer Incidence by Site United States. Siegal Et al: CA journal, January 2018 2

Deaths from Cancer Averted by Screening and Treatments Siegal Et al: CA Journal, January 2018 Screening Average and low risk patients Goals : early detection and reducing morbidity and morality 3

Harms of Screening Over diagnosis False Positives Increased testing False reassurances Anxiety Cost Guidelines USPSTF ACP ACR ACOG ASCO NCCN International organizations 4

USPSTF guidelines It is an independed bout Grades of Evidence Grade A B C D I Definition Recommends the service with high certainly that net benefit is substantial Recommends the service with high certainty of moderate benefit or moderate certainty that net benefit is moderate substantial Recommend selectively offering the service based on patient preference and professional judgment. There is at least moderate certainty that net benefit is small Recommends against the service. There is moderate to high certainly that service has no benefit or that harms outweigh the benefit Current evidence is insufficient to assess benefits and harms of the service. 5

Breast Cancer Most common cancer in women. Estimated incidence in 2018; 266,120 Estimated deaths in 2018 ; 40,920 5 year survival : 89.5% % of all cancer deaths : 8.3% Risk increases with age. Breast Cancer Incidence trends SEER Database 6

Trends in death rate 1972-2012 SEER Database Who Should be Screened Screening recommendation only apply to women who are age 40 or older Who do no have preexisting breast cancer or a high risk breast lesion, Who do not have an underlying genetic mutation. Or a history of chest radiation at young age. 7

Screening Guidelines for Breast Cancer: A Confusing Mess Mammographic screening When should you start - 40/ 45 /50 years of age. How frequent: every year or every 2 years Who should be considered for earlier screening. There are some important caveats to guidelines to consider. USPSTF Breast Cancer Screening: Mammography;2016 Population Recommendation Grade Women age 50-75 years Biennial screening B Women, 40-49 years Individualized decision after discussing potential benefits and risks. For average risk women, the benefit may be smaller. Women with family history, parent, sibling or child with breast cancer are at higher risk and may benefit from starting screening in their 40s. C Women, 75 years or older Insufficient evidence to assess the benefits and harms in women 75 or older. I 8

Mammography Population Recomendation Grade All women Current evidence insufficient for digital breast tomosynthesis (DBT) as a primary screening method. I Women with dense breasts Current evidence is insufficient for adjunctive screening for breast cancer using breast ultrasonography, MRI, DBT in women identified to have dense breasts. I USPSTF guidelines: SBE, CBE 2013 Population Recommendations Grade All women Against self breast D examination Women, 40 years or older All women Insufficient evidence of clinical breast exam Insufficient evidence for digital mammography or MRI as screening modalities. This was not addressed again in 2016 as digital mammography is not widely available. I I 9

Breast Cancer Screening: American Cancer Society Population Recommendation Strength 45-54 Mammography annually Strong recommendation 55 and older Biennial mammography Qualified recommendation 40-44 years Women should have the opportunity to begin screening at 40-44 years All women Should have the opportunity for screening as long as their overall health is good and life expectancy of 10 years. Qualified recommendations Qualified All women Does not recommend CBE in all women at average risk Qualified recommendations American College of Radiology/ Society of Breast Imaging : 2018 Average risk women should continue to begin screening at age 40. Non Hispanic White and non Hispanic Black women have the highest risk of breast cancer and their risk of breast cancer is now similar. nhb have higher risk of death from breast cancer. All women especially nhb and women of Ashkenazi Jewish descent should be evaluated for breast cancer risk no later than age of 30. Monticciolo et al; JACR2018 10

Why are guidelines different for women in their benefit USPSTF estimates 8% mortality benefit ACS; estimates 15% Screening women at age 40 versus 50 averts one death per 1000 women. Most averted death are between 45-49 years of age which prompted the ACS recommendation What makes a person high risk? History of chest radiation (RR 26.0) History of breast cancer (RR varies) History biopsy with atypical hyperplasia (3.7) Two 1 st -degree relatives with breast cancer vs none (RR 3.5) One 1st-degree relative with breast cancer vs none (RR 2.5) Menopause >55 y compared with <45 y (RR 2.0) Nulliparity or 1 st full-term pregnancy 30 y (RR 2.0) History benign breast biopsy vs no breast biopsy (RR 1.7) co 11

Menarche before age 12 years compared with >14 y (RR 1.5) Postmenopausal obesity vs normal weight (RR 1.5) Heterogeneously dense or extremely dense breasts compared with fatty or fibroglandular breasts (RR 1.3) Current use of combination menopausal hormone therapy vs never users (RR 1.2) Moderate alcohol use compared with abstention (RR 1.1) Risk Assessment Tools? NCI Breast Cancer Risk Assessment Tool/Gail Model Has been used in the studies to assess for chemo prevention but not for screening Breast Cancer Surveillance Consortium Includes breast density and may not be helpful initial screening decisions Ontario Family History Assessment tool, Manchester Scoring System, Family History Screen 7 All useful for women with family histories of breast cancer 12

Decision aids Help clinicians and patients understand risk estimates Use to facilitate conversations, not to make decisions : www.breastscreeningdecisions.com Helps patient visualize their risks and can be used for discussions. Breast Cancer Guidelines: Summary All women at average risk can begin screening at 50 years of age, biennial screening is adequate. All women should have a risk assessment with family history and risk factors in to account no later than 30. For women with 40-49 years, risk factors, patient preference become really important. There is very little data on racial and ethnic minorities. This should be considered in decision making. For women with dense breasts, there are no guidelines. However, individual risk factors should be used as a guide. 13

WISDOM Study : Ongoing WISDOM; Women Informed to Screen Depending on Measures of Risk Annual Mammograms versus more personalized approach based on risks. Plans to recruit 100,000 women in California. Randomized to personalized or annual screening. Personalized arm will be assessed for breast cancer risk and given a genetic test. 14

USPSTF: Cervical Cancer Population Recommendation Grade Women 21-65( pap smear) 30-65 ( in combo with HPV testing) HPV testing in women younger than 30 years Cervical cancer Screening with PAP smear with cytology every 3 years for women 21-65 years, and for woman 30-65 years PAP smear and HPV cotesting screening interval can be lengthened to every 5 years. Recommend against screening with HPV testing A D Women younger than 21 years Women older than 65 years who have had prior adequate screening Women who have had hysterectomy Recommend against routine screening Recommends against routine screening in women age 65 years or older who have had adequate screening. ( this will exclude women who have no documented screening, immunocompromised and women with history of high grade precancerousema lesions) Recommends against routine screening for woman who have had a hysterectomy with removal of cervix and who do nota have a history of CIN grade 2 or 3 or cervical cancer. D D Draft guidelines; USPSTF (Sep 2017) 15

ACS cervical cancer screening : 2016 Population Women 21-29 years of age Recommendation Pap test every 3 years. No HPV testing in this group Women 30-65 PAP + HPV testing every 5 years is preferred and PAP test every 3 years is a reasonable option Women over 65 years who have regular screening Women of any age Women who have received HPV vaccination Routine screening is not recommended Should NOT be screened every year by any method Follow guidelines as other patients ACOG Co-testing every 5 years is the preferred approach in women with 30-65 years of age. Cytology every 3 years is an acceptable alternative. Other recommendations are not different. 16

Screening women with HIV Screening should begin at age of sexual activity and no later than age 21 Regardless of mode of HIV transmission If less than age 30,screening with cytology annually and if 3 consecutive screens are normal, then cytology can be every 3 years. For age 30 and older recommendation as above or if the cotest is negative can be screened every 3 years. USPSTF Prostate Cancer In May 2012, USPSTF recommended against Prostate cancer screening with a D recommendation. Current draft recommendations are for individualizing the decision for man 55-69 with grade C and recommends against screening in man older than 70 years of age. 17

American Cancer Society : 2016 The recommendations from American Cancer society is for men to have a chance to make an informed decision about PSA screening with their provider about uncertainties, potential benefits and risks of screening. This discussion should take place at. Age 50 for men at average risk and expected to live at least 10 more years. Age 45 for me at higher risk of developing prostate cancer. This included African Americans and men who have a first degree relative diagnosed with prostate cancer at an early age( Younger than 65). Age 40 for men at even higher risk ( Those with more than one first degree relative who had prostate cancer at early age). Prostate Cancer: ACS Men who choose to be screened should be tested with Prostate Specific Antigen and DRE may also be done as part of screening. Men who choose to be tested and have a PSA of less than 2.5ng/mL only need to be tested every 2 years. Screening should be yearly for patient with PSA of greater than 2.5ng/mL. 18

Prostate Cancer/AUA Population Recommendation Grade Men under age of 40 Against screening C 40-54 years No routine screening consider in high C risk patients 55-69 years Shared decision making B Frequency in screened patients Every two years C Men 70+years of age or life expectancy less than 10-15 years Does not recommend routine PSA screening C Colorectal Cancer Estimated new cases 2018; 140,250 Estimated deaths; 50,630 % of cancer deaths 8.3% 19

Colorectal Cancer screening: USPSTF Population Recommendation Grade Adults age 50-75 years Adults aged 75-85 years Recommends for screening starting at age 50 and continuing until 75 years. Should be an individual and should take in to account overall health and prior screening history A C US Preventive Services Task Force. Screening for Colorectal CancerUS Preventive Services Task Force Recommendation Statement. JAMA. 2016;315(23):2564 2575. doi:10.1001/jama.2016.5989 Screening methods: Stool Based Tests Screening method Frequency Evidence Other considerations gfobt Every Year RCT with morality end point FIT Every year Improved accuracy compared with FOBT. Can be done with single specimen FIT-DNA Every 1-3 years More false positives leading to more colonoscopies and more associated adverse events No bowel prep, anaesthesia, transportation required No bowel prep, anaesthesia, transportation required Insufficient evidence of longitudinal follow up after negative colonoscopy. 20

Screening tests: Direct Visualizations Tests Screening Methods Frequency Evidence of Efficacy Colonoscopy Every 10 years Prospective cohort study with mortality end pont Other considerations Less frequent screening but needs prep. CT colonography Every 5 years Insufficient evidence of harms from associated extra colonic findings Flexible sigmoidoscopy Flexible sigmoidoscopy +FIT Every 5 years Flex sig every 10 years plus FIT annually RCT with mortality end points RCT with mortality end point Availability has declined in the US Availability has declined in the US 21

American Cancer society : CRC screening Recommends screening at age 50 years and recommendation are similar to USPSTF Tests Colonsocpy CT colonography Felixibe sigmoidoscopy Double contrast BA enema FIT gfobt Stool DNA Every 10 years Every 5 years Every 5 years Every 5 years Every year Every year Every three years Consideration in Colon Cancer Screening Best test is what gets done. Keep patient considerations in mind when choosing a screening tests for colon cancer. Colonoscopy as gold Standard should not keep you from using stool based tests if the patients prefer that. 22

Lung Cancer Number one cause of cancer deaths in both men and women Estimated new cases in 2018 : 234,000 Estimated deaths : 154,050 25% of all cancer deaths Lung Cancer: USPSTF Population Recommendation Grade Adults age 55-80 years with significant history of smoking USPSTF recommends annual screening for lung cancer with low-dose computed tomography (LDCT) in adults aged 55-80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years. B Screening should be discontinued for adults who have quit smoking for more than 15 years or are not candidates for curative surgery. 23

American Thoracic Society Potential Benefits Mortality Benefit : 20% relative risk reduction in ling cancer deaths ( from 1.66% to 1.33%) 7% relative risk reduction from all cause mortality Psychosocial benefits and behavioral changes Smoking cessation Reassurance if normal CT Potential Harms Harms related to test: Radiation exposure False reassurance; Aggressive tumors can develop in the interim Over diagnosis ( 15-20% of all tumors detected) False positive and other incidental findings. Potential harms from downstream tessting Lung cancer Screening Lung cancer screening has institutional requirements LDCT should be available Experienced radiologist Expertise in pulmonary, cardiothoracic surgery Patients should be candidate for curative surgery. Smoking cessation should be available. 24

SEER Database American Cancer Society This guideline recommends that clinicians with access to high volume, high quality lung cancer screening and treatment centers should initiate a discussion about screening with apparently healthy patients aged 55 years to 74 years who have at least a 30 pack year smoking history and who currently smoke or have quit within the past 15 years. After quitting smoking for 10 years risk of dying from lung cancer is cut in to half. Screening should not be seen as an alternative to smoking cessation. The biggest impact in lung cancer mortality will not come from screening but from smoking cessation. 25

Skin Cancer Screening Poulatioon Reommendation Grade Asymptomatic adults Current evidence in insufficient to assess benefits and risk of visual examination by a clinician to screen for skin cancer I US Preventive Services Task Force. Screening for Skin CancerUS Preventive Services Task Force Recommendation Statement. JAMA. 2016;316(4):429 435. doi:10.1001/jama.2016.8465 Questions Thank you 26