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

2. Prevention Onset of disease Clinical diagnosis Healthy Asymptomatic
Clinical course
Primary
Elimination of risk factor
Cessation of smoking
Colonoscopy
Vaccination
Lifestyle modifications
Secondary
Early diagnosis and treatment
Colonoscopy
Mamography
Pap smear
Tertiary
Reducing complications (rehabilitation)
Primer korunma için geç.
Sigarayı bırakmak morbiditeyi azaltabilir.
Sigmoidoskopi: Hem primer, hem de sekonder

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
Applied to asymptomatic groups
Applied to symptomatic individuals
Lower cost per test
Higher cost, all necessary tests applied to identify disease
Lower yield per test
Increased probability of case detection
Lower adverse consequences of error
Failure to identify true positive can delay treatment, worsen prognosis

5. Ideal screening program
Requirements of screening test
Diagnosing disease at preclinical phase
Acceptable sensitivity and specificy
Acceptable to people
Simple anf cheap
Safe
Patient features
High impact: Morbidity, mortality, economy
High incidance and high prevelance
Predictable corse and biology
High prevelance of preclinic phase
Effective treatment exists
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 Screening Average 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
Cervical Cytologic Screening Guidelines from the American College of Obstetricians and Gynecologists, 2009.
Sawaya G. N Engl J Med 2009; /NEJMp

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 cancer Average 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 Target population: Age: 55-74 years +
Smoked ≥ 30 pack/year +
Continue to smoke or have quitted smoking within 15 years
Screeninig method: Low dose thorax CT

25. Hepatocellular Carcinoma
No cirrhosis
Hepatitis B carrier
Non-alcoholic steatohepatitis
Cirrhosis
Hepatitis B, C
Alcohol
Genetic hemocromatosis
Non-alcoholic steatohepatitis
Autoimmune hepatitis
Primary biliary cirrhosis
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.