CANCER SCREENING USPSTF AND BEYOND. DeAnn Cummings, MD March 9, 2019

CANCER SCREENING USPSTF AND BEYOND DeAnn Cummings, MD March 9, 2019

OBJECTIVES Review and discuss cancer screening guidelines for: Colorectal CA Prostate CA Breast CA Ovarian CA Secondary prevention, NOT primary prevention

CASE #1 45 year old African American male in your office for a physical. His wife made him come in. He feels well and has no complaints. ROS completely negative PMH none PSH none Meds - none

Social history Smokes ½ ppd for 20 years (trying to quit) No alcohol, no drugs He is an attorney. Married with 2 children CASE #1

CASE #1 Family history Father colon polyps at age 50, prostate CA age 60 Mother CAD, HTN, DM Paternal Grandfather colon CA at age 55 Brother age 50 HTN, DM, elevated PSA, has not yet had colonoscopy

Physical exam BMI = 33, BP = 130/80, HR = 90 Other than obesity, his exam is normal. Rectal and genital exam not done. CASE #1

His wife thinks he should get a PSA. What do you think? CASE #1

PROSTATE CANCER SCREENING

USPSTF 2018 Recommendations Men age 55-69 shared decision making Men age 70 or greater no screening 2012 Recommendations No screening D What changed their thinking? D C

USPSTF 2018 Previously the harm of unnecessary testing and treatment outweighed the benefit of finding a cancer early and treating it. New study (ERSPC) Screening prevents 1-2/1000 men from dying from prostate CA and 3/1000 men from developing metastatic CA Urology guidelines now encourage active surveillance of elevated PSA rather than aggressive treatment.

USPSTF 2018 No recommendations could be made for men at higher risk who are less than 55 African American Family history first degree relative with advanced prostate CA, metastatic CA or died from prostate CA More studies needed in these groups

AUA GUIDELINES 2013 Recommendations Men age < 40 No screening (Grade C) Men age 40-54 IF average risk, no screening. Shared decision making if African American or positive family hx (Grade C) Men age 55-69 Shared decision making. Consider PSA every 2 years instead of yearly (Grade B) Men age 70 or greater If life expectancy < 10-15 yrs, do not screen (Grade C)

AUA GUIDELINES 2013 Why start screening at 55? 99% deaths from prostate CA occur after age 54 Family history Men with one first degree relative with prostate CA have increased risk by 30%. Prostate, breast, ovarian, pancreatic CA in multiple family members and/or at younger ages If family member had advanced disease at diagnosis or died of prostate CA, there may be increased benefit from screening.

AUA GUIDELINES 2013 African American 44.1 deaths/100,000 vs 19.1 deaths/100,000 for white men Trials had small number of African American patients May be benefit to screening at < age 55 Probably no benefit to screening after age 70

AUA GUIDELINES 2013 PSA level and interval of screening If PSA < 1, could screen every 4 years If PSA is 1-4, screen every 2 years For men over 70, if PSA is < 3, can stop screening Rationale for every 2 year instead of yearly screen Less harm from unnecessary testing and treatment No sig reduction in benefit

AUA GUIDELINES 2013 Harm For every 1000 men screened 2 serious cardiovascular event 1 DVT or PE 29 erectile dysfunction 18 incontinence 1 death Less serious hematuria, pain, worry, prostatitis

CASE #1 Our patient Age 45 African American Father with prostate CA but don t know details Brother with elevated PSA but don t know details

How do we have a discussion with our patient? Will we sway him one way or the other? What if he had the same family history but was white? CASE #1

Tough to find time!! Resources USPSTF video USPSTF handout SHARED DECISION MAKING

CASE #1 After discussion, our patient (and his wife) decide to get the PSA. Now they are wondering about colon CA screening since this runs in the family Paternal grandfather with colon CA at age 55 Father with colon polyps removed at age 50

COLON CANCER SCREENING

USPSTF 2016 All patients age 50-75 should be offered screening (A) For patient age 76 85 consider life expectancy, ability to undergo treatment and hx previous screening. (C) More benefit in those who have not had regular screening No point in screening if patient is not in good enough shape for surgery. ABOVE APPLIES TO AVERAGE RISK PATIENTS ONLY

US MULTI-SOCIETY TASK FORCE 2017 American College of Gastroenterology American Gastroenterological Association American Society for Gastrointestinal Endoscopy

MSTF 2017 Guidelines based on studies that did NOT include patients with inflammatory bowel disease, prior CRC or polyps, or hereditary CRC syndromes (familial polyposis, Lynch syndrome)

What are we looking for in screening? Advanced adenoma (70% of all CRC) Lesions 1 cm or more in size Lesions with high grade dysplasia Lesions with villous elements Serrated colorectal lesions (30% of all CRC) Sessile serrated polyps (SSPs) Often flat, less vascular and proximal MSTF 2017

MSTF 2017 Offer CRC screening for average-risk patients at age 50 (Strong) 3 options for presenting screening test choices Offer multiple screening options (2 or more) Offer sequential ordering of screening tests Risk stratified approach encourage colonoscopy for higher risk patients

Screening test options Colonoscopy PROS Potential to diagnose and treat all in one test Won t need additional clean outs! Can find polyps in both right and left colon Can find sessile polyps Screening is less frequent MSTF 2017

Screening test options Colonoscopy CONS Need thorough bowel cleansing Risk of perforation (0.5/1000) Risk of bleeding (2.6/1000) Risk of aspiration if sedated Risk of death (2.9/100,000) MSTF 2017

MSTF 2017 Screening test options Colonoscopy CONS Operator dependence in performance Adenoma detection rate should be 25% or more Cecal intubation rate 90% or more overall Should use split dose bowel prep (half of prep given on day of colonoscopy) Report afterwards should include photos of the end of the colon and describe bowel prep quality

MSTF 2017 Fecal immunochemical test (FIT) PROS No prep! $20 Sensitivity for cancer of 79%, sensitivity for advanced adenoma of 30% FIT test CONS Need yearly testing Poor sensitivity for SSPs (once dysplastic or cancerous, more likely to be picked up

MSTF 2017 FIT-fecal DNA test (Cologuard) PROS No prep! Good sensitivity for CRC (92%) 40% sensitivity for SSPs Every 3 year testing FIT-fecal DNA test CONS Decrease in specificity vs FIT alone (86% vs 96%) High cost - $500-600 Higher number of colonoscopies per test

MSTF 2017 CT Colonography PROS 82 92% sensitivity for adenomas > 1cm Lower risk of perforation than colonoscopy Testing every 5 years CT Colonography CONS Need for bowel prep (otherwise decreased sensitivity) Difficult to detect small and flat lesions (SSPs) Detection of extracolonic incidental findings Patients with polyps 6 mm or more will need colonoscopy

MSTF 2017 Flexible sigmoidoscopy PROS Decreases DISTAL cancer incidence and mortality No need for sedation, less bowel prep, less risk than colonoscopy Screen every 5-10 years (favor 10 years) Flexible sigmoidoscopy CONS Does not detect proximal disease Less patient satisfaction due to no sedation

MSTF 2017 Capsule colonoscopy PROS Can be done in patients who should not get sedation 88% sensitivity for adenomas 6 mm or more May avoid risks of colonoscopy Capsule colonoscopy CONS Extensive bowel prep required Cannot detect SSPs Poor reimbursement Will need colonoscopy anyway if positive

MSTF 2017 Septin9 serum assay Sensitivity of 48% for detection of CRC No sensitivity for detection of precancerous polyps NOT recommended

3 Tiers Tier 1 Colonoscopy every 10 years Annual FIT Tier 2 CT colonography every 5 years FIT-fecal DNA every 3 years Flex sig every 10 years (or every 5 years) Tier 3 Capsule colonoscopy every 5 years MSTF GUIDELINES

MSTF GUIDELINES Average risk patients should be offered screening at age 50 (Strong) What about higher risk patients? Family history of CRC or advanced adenomas Cig smoking Diabetes Obesity African American

MSTF GUIDELINES 2017 One first degree relative with CRC or a documented advanced adenoma at age < 60 OR two first degree relatives at any age Colonoscopy every 5 years beginning 10 years prior to diagnosis of family member or age 40, whichever is earlier. (Weak)

MSTF GUIDELINES 2017 One first degree relative diagnosed at age 60 or greater with CRC or advanced adenoma Colonoscopy every 10 years, starting at age 40 (Weak) One or more first degree relatives with an advanced serrated lesion Same as for advanced adenomas (Weak)

MSTF GUIDELINES 2017 Need additional study to know what to do with diabetics, smokers or obese patients African American (CRC at younger age, increased incidence) 2 of the member organizations endorse screening at age 45 even if average risk American College of Physicians endorse screening at age 40

MSTF GUIDELINES Increasing incidence of CRC in people < 50 Aggressive evaluation of patients with colorectal symptoms, especially bleeding (Strong) When to stop? Screening may be beneficial up to age 86 if there has not been previous screening but must consider comorbidities and life expectancy. (Weak) Consider stopping at age 75 if pt has had previous screening (Weak)

AMERICAN CANCER SOCIETY 2018 Now recommend screening AVERAGE risk people 45 and older for colorectal CA! Rationale Incidence of colorectal CA in people 40-50 is steadily increasing

CASE #1 Our patient s father had colon polyps at age 50. He does not know what kind of polyps they were. Grandfather with CRC at age 55 Also a smoker and obese and African American What do you recommend?

CASE #2 Polly is a 50 year old white female who presents for a well visit. She, at least initially, has no complaints. She is married with 2 children who are both in college. She works as a nurse in a primary care office. She tells you she just turned 50 and wants to get checked out.

OUR PATIENT PMH GERD Mild depression PSH Appendectomy Meds Omeprazole x 10 years Prozac x 5 years Multivitamin, vitamin E, calcium, vitamin D, vitamin B12

OUR PATIENT Social History Never smoker Occasional glass of wine No drugs Family History Mom Living. Had MI at age 55. Dad Living. Has COPD. Sister Breast cancer at age 50. Maternal grandmother Ovarian cancer

OUR PATIENT GYN History G2P2 Both deliveries were vaginal and at term. First delivery was at age 24. She has used a copper IUD since the birth of her last child. She used oral contraceptives prior to having children. Menarche was at age 11. She has not had her period in 6 months.

OUR PATIENT EXAM BP = 120/70, HR = 92, RR = 16, Weight = 125 lbs, Height = 5 5 BMI = 20.8 HEENT unremarkable Skin unremarkable (How thorough are you?) Neck no adenopathy or thyromegaly Lungs decreased breath sounds at bases but clear Heart Regular S1S2, no murmurs Abdomen unremarkable Extremities good pulses, no edema

BREAST EXAM Will our patient benefit from a clinical breast exam?

BREAST EXAM All recommendations agree that clinical breast exam is not indicated for average-risk women. It may be valuable in high-risk women on a yearly basis. Is our patient high risk?

BREAST EXAM Gail assessment tool (NIH Breast Cancer Risk Assessment Tool) Age 50 Menarche 11 years First live birth at 20-24 years old One first degree relative with breast CA No previous breast biopsy White 2.0% 5-year breast cancer risk compared to 1.3% for average 50 year old (high risk if > 1.7%) 17.9% lifetime risk (high risk if > 15-20%)

PELVIC EXAM AND PAP SMEAR Will our patient benefit from a pelvic exam? Does she need a pap smear? She has been seeing her OB-GYN who gets yearly pap smears. She is now coming to you for GYN care. Last pap was one year ago. She has no history of an abnormal pap smear.

CERVICAL CANCER SCREENING ASCCP, ACOG and ACS Recommendations - 2012 Pap and HPV testing every 5 years (preferred) OR pap every 3 years for women 30 years old or more Stop screening at age 65 if adequate prior screening and no CIN 2 or 3 in the past 20 years USPSTF - 2017 Pap every 3 years OR HPV test every 5 years for women 30-65 Same recommendation as above for women over 65

CERVICAL CANCER SCREENING How do you convince her that she doesn t need pap smears every year? She tells you her GYN told her she is high risk from her family history.

CERVICAL CANCER SCREENING How do you convince her that she doesn t need pap smears every year? She tells you her GYN told her she is high risk from her family history.

OUR PATIENT You do a clinical breast exam which is normal. You convince her she does not need a pap and pelvic. However, she is very worried about her family history of breast and ovarian cancer. She would like any available tests to help detect these cancers. She has had yearly mammograms since age 40. Does she need genetic testing for BRCA?

GENETIC TESTING USPSTF recommends using a screening tool to determine who needs genetic testing (start age 18 and update every 5-10 years) Referral Screening Tool FHS-7 Ontario Family History Assessment Tool Manchester Scoring System Pedigree Assessment Tool CANNOT use Gail Model to determine who needs genetic testing

GENETIC TESTING NATIONAL COMPREHENSIVE CANCER NETWORK 2019 Anyone with male breast CA, personal or family hx Anyone with 2 separate primary breast cancers, personal or family hx Anyone with 2 or more relatives with breast CA and personal hx breast CA Anyone with 3 or more relatives with breast CA Anyone with ovarian CA, advanced prostate CA or pancreatic CA (BRCA 2), personal or family hx Anyone with breast CA at age 50 or less, personal or FH Ashkenazi Jew with breast or advanced prostate CA

BREAST CANCER SCREENING GUIDELINES FOR AVERAGE RISK WOMEN USPSTF (2016), AAFP (2016) Screen women ages 50-74 every 2 years (B) Shared decision-making for ages 40-49 (may be more value in screening 45-49 year olds) (C)? Continue beyond age 75 (I) ACOG (2016), ACP (2015) Same as above BUT screening can be every 1 or 2 years

BREAST CANCER SCREENING ACS (2015) Screen women 45-54 every year Screen women over 54 every one-two years Decision about when to stop should be based on patient s comorbidities and life expectancy.

BREAST CANCER SCREENING HARMS Overdiagnosis For every woman who avoids a death from breast CA, 2-3 will be treated unnecessarily Increased risk if start screening at earlier age or screen every year False-positive results Risk of radiation small but digital breast tomosynthesis (3D mammo) doubles radiation exposure

BREAST CANCER SCREENING BRCA- positive women (ACOG) Clinical breast exam every 6-12 months Yearly MRI at ages 25 29 After age 30, yearly MRI and mammo Consider prophylaxis (med or surgery) BRCA increases risk of breast CA by 45-65% BRCA increases risk of ovarian CA by 39%

BREAST CANCER SCREENING What about high risk women who have negative genetic testing? Recommend yearly mammogram, MRI and CBE if life-time breast CA risk is 20% or more (our patient is 17.9%) ACS consider above if life-time risk is 15-20% If 5 year risk is 1.7% or more, consider tamoxifen or raloxifene prophylaxis (decreases breast CA by 50%) Our patient has a 5 year risk of 2%

OVARIAN CANCER SCREENING Transvaginal pelvic ultrasound Sensitive but poor specificity CA 125 Elevated in 50% of early ovarian CA patients Elevated in 80% of advanced ovarian CA patients Specificity = 98-99% Human Epididymis Protein 4 (HE4) Positive in 32% of patients with CA125 negative ovarian CA Symptom Index

OVARIAN CANCER SCREENING Symptom Index Bloating or increased abdominal size Abdominal or pelvic pain Difficulty eating or early satiety These symptoms must be new within the last 12 months and occur 12x per month or more. If you have one of these symptoms, consider getting CA 125 and HE4. If either of these is positive, check TVUS.

OVARIAN CANCER SCREENING All groups do not recommend screening average-risk women for ovarian CA Ovarian CA has a low incidence (40/100,000) A screening test would need a specificity of 99.6% to get a PPV of 10%. Otherwise there will be too many false positives and therefore too many unnecessary procedures. High risk but BRCA negative High risk, BRCA positive

OVARIAN CANCER SCREENING High risk BRCA positive Encourage prophylactic salpingo-oophorectomy if done having children Otherwise expert opinion suggests yearly CA125 and transvaginal pelvic US starting at age 35 Studies are ongoing

OVARIAN CANCER SCREENING High risk BRCA negative Does not appear to be any benefit to screening however studies are ongoing.

OUR PATIENT She gets tested for BRCA and it is negative so she is intermediate to high risk BRCA negative. You recommend she continue with yearly mammograms and clinical breast exams and discuss the pros and cons of MRI. (and whether or not insurance covers it!) You also discuss tamoxifen. No ovarian cancer screening. Risk will need to be reassessed on a regular basis.

OUR PATIENT She gets her mammogram and it is read as negative but the report states she has extremely dense breasts. What do you do with this info?

DENSE BREASTS 43% women ages 40-74 will have heterogeneously dense breasts or extremely dense breasts on mammo Increases risk of breast CA slightly (0.7% to 1.3% 5- year risk) Decreases sensitivity and specificity of mammo Sensitivity - 87% to 63% Specificity - 96% to 90%

DENSE BREASTS Several states have laws mandating that women are informed if there mammo shows dense breasts HOWEVER, there is NO mandate that insurance companies cover further screening with MRI

DENSE BREASTS No clear evidence for supplemental MRI or ultrasound in these women and guidelines are not presently recommending this. (Too many falsepositives!) Large international trial is underway (DENSE trial) for supplementation with MRI.

GENERAL TAKE-AWAYS We really need to get a detailed FAMILY HISTORY starting at age 18 and update it regularly. We need a plan for how to accomplish SHARED DECISION-MAKING. Must look at an individual s risk to determine appropriate screening. SCREENING IS NOT THE SAME FOR EVERYONE! Lower threshold than in the past for referral to a GENETIC COUNSELOR.