Screening and Early Diagnosis in Oncology

1. Screening and Early Diagnosis in Oncology Başak Oyan-Uluç, MD Yeditepe University Hospital Department of Medical Oncology

2. Primary Elimination of risk factor Cessation of smoking Colonoscopy Vaccination Lifestyle modifications Prevention Onset of disease Clinical diagnosis Healthy Asymptomatic Clinical course Secondary Early diagnosis and treatment • Colonoscopy • Mamography • Pap smear Tertiary Reducing complications (rehabilitation)

3. Cancer Screening • Cancer screening: Early detection of asymptomatic or unrecognized disease by the application of inexpensive tests or examinations in a large number of people. • Main objective: To reduce morbidity and mortality from a particular cancer among people screened. • Screening procedure itself • Not diagnostic • Detects people with cancer risk • Positive or suspicious findings must be evaluated further to determine diagnosis and appropriate treatment.

4. Screening vs. Diagnosis

5. Patient features High impact: Morbidity, mortality, economy High incidance and high prevelance Predictable corse and biology High prevelance of preclinic phase Effective treatment exists Requirements of screening test Diagnosing disease at preclinical phase Acceptable sensitivity and specificy Acceptable to people Simple anf cheap Safe Ideal screening program Quality of primary or secondary prevention (Cheap, effective, safe)

6. Benefits of Screening • Improved prognosis for those with early-detected cancers • Less radical treatment • Reassurance for those with negative test results • Reduction of treatment costs

7. Hazards of screening • The potential for overdiagnosis (Labelling phenomenon) • The potential carcinogenic effects of screening (i.e. Radiation risk with mammography) • The economic consequences of false-negatives

8. Cervical Cancer-Pap Smear • Long preinvasive period • Increased morbidity and mortality in invasive period • Treatable if early diagnosis • PAP smear: Sensitive, low cost, easy to apply, safe

9. Cancers suitable for screening • Although there are more than 100 different cancers, most of them lack proven screening interventions • Cancers that have widely accepted screening interventions • Breast • Cervix • Colorectal • Prostate ? • Hepatocellular cancer in patients with risk factor • Lung cancer in people with defined risk factors

10. Breast Cancer Screening • Most common cancer in females • Average risk • Increased risk • Prior thoracic RT (eg. Mantle) • Women who have a lifetime risk of >%20 • Strong family history of genetic predisposition • LCIS/atypical hyperplasia • Prior history of breast cancer

11. Breast Cancer ScreeningAverage risk women Widely accepted techniques for breast cancer screening includes • Brest self-examination: Monthly after age 20 • Clinical breast examination: • Age 20-39: Every 1-3 years • Every year after age 40 • Mamography: Every year after age 40 • Decrease mortality by 20-30%

12. Cervical Cancer Screening • Second most common cancer in females worldwide particularly in the underdeveloped regions • The incidence has declined in many countries due to the improved standard of living throughout the world

13. Cervical Cancer Screening • Pap test: Introduced in 1930s by Dr. Papanicolaou • Screening should begin at age 21 • Discontinuation of screening • At age 65-70, if 3 negative tests and no abnormal tests in preceeding 10 years • Screening not discontinued in • In-uterine DES exposure • Personal history of servical cancer • Immune insuffiency (eg. HIV) • HPV DNA (+)

14. Cervical Cytologic Screening Guidelines from the American College of Obstetricians and Gynecologists, 2009 Sawaya G. N Engl J Med 2009;10.1056/NEJMp0911380

15. Colorectal Cancer Screening • Causes morbidity and mortality in both men and women • Second leading cause of death due to cancer • The natural history of colon cancer with relatively long time from biologic onset to development of carcinoma makes it a good candidate for screening

16. Risk groups for screening • Average risk • Age ≥ 50 y • No inflammatoy bowel disease • No history of adenoma or colorectal cancer • Negative family history • Increased risk • Personal history of • Adenoma/sessile serrated polyp • Inflammatoy bowel disease • Colorectal cancer • Positive family history • High risk syndromes • Lynch syndrome/Hereditary nonpolyposis colorectal cancer (HNPCC) • Polyposis syndromes (familial adenomatous polyposis, Peutz-Jeggers syndrome, Juvenile polyposis syndrome, hyperplastic polyposis syndrome)

17. Screening tests for colorectal cancerAverage risk Starts at age 50 1. Colonoscopy every 10 years • preferred if available • For every 1% increase in complete colonoscopy rate, the hazard of death decreased by 3%. 2. Annual FOBT+Flexible sigmoidoscopy every 5 years Annual Fecal occult blood test (FOBT) • Testing of stool for occult blood to detect colorectal cancer at an early stage • Variation is observed in estimates of the sensitivity but its lower cost and increased specificity to detect right-isded colonic lesions make it a good screening test Flexible sigmoidoscopy every 5 years • In contrast to FOBT, has a high sensitivity and specificity • Involves the use of a 60 cm flexible sigmoidoscope • Detects left sided lesions

18. Prostate Cancer Screening • Most commonly diagnosed cancer among men and is the second leading cause of male cancer deaths • Two main screening modalities • Serum prostate specific antigen (PSA) • Digital rectal examination (DRE)

19. Prostate Cancer Screening • Benefit of screening is controversial • Prostate cancer is common and potentially lethal; however, more patients die with, rather than from, the disease. • Incidence: 1/6 Mortality: 1/30 • Screening detects more cases of organ-confined disease, but there is no proof that this detection saves lives. • In more instances, prostate cancer is not the cause of elevated PSA level. NEJM 2009; 360:1310 NEJM 2009; 360:1320

20. Prostate Cancer Screening • Localized treatment of prostate cancer is effective but is associated with complications than can include impotence and incontinence (~ 50%). • It is likely that prostate cancer screening using the PSA level is beneficial in a subset of men; however, the characteristics of the subset have not been defined.

21. Prostate Cancer Screening • Discuss benefit and harms of screening with the patient • In men with a life expectancy of >10 years, start annual screening at age 40y with: • PSA • Digital rectal examination • In last years it is recommended to offer a baseline DRE and PSA at age 40 y.

22. Prostate Cancer Screening • DRE • Most widely used and oldest technique for detection of prostate cancer • Wide ranges of sensitivity (33%-69%) and specificity (49%-97%) • Serum PSA level • Allows earlier detection of prostate cancer • Normal PSA values are found in 1/3 of localized tumors (false negative) • Often elevated in men with noncancerous conditions such as benign prostatic hyperplasia (false positive)

23. Prostate Cancer Screening • NCCN recommendation • DRE yearly starting at age 40 • PSA yearly starting at age 40

24. Lung Cancer Screening Targetpopulation: • Age: 55-74 years + • Smoked ≥ 30 pack/year + • Continuetosmokeorhavequittedsmokingwithin 15 years Screeninigmethod: Lowdosethorax CT

25. Cirrhosis Hepatitis B, C Alcohol Genetic hemocromatosis Non-alcoholic steatohepatitis Autoimmune hepatitis Primary biliary cirrhosis No cirrhosis Hepatitis B carrier Non-alcoholic steatohepatitis Hepatocellular Carcinoma Diagnosis rate: %92 False (+): %7.5 Ultrasonography Alpha-feto protein (AFP) Every 6-12 months

26. People not to be screened • Life expectancy <5 years • People who do not wish to undergo additional diagnostic tests or who do not want any treatment

27. Future of Screening • Compliance: Encourage people to adhere the proven cancer screening modalities • New and better methods: With the discovery of cancer susceptibility genes (e.g. BRCA-1 susceptibility gene for breast cancer) lifetime risk for an individual to develop a specific cancer could be estimated.