Screening and Early

Diagnosis in Oncology

Başak Oyan-Uluç, MDYeditepe University Hospital

Department of Medical Oncology

Prevention

PrimaryElimination of

risk factor• Cessation of

smoking• Colonoscopy• Vaccination• Lifestyle

modifications

Onset of disease Clinical diagnosis

Asymptomatic Clinical courseHealthy

SecondaryEarly diagnosis

and treatment• Colonoscopy

• Mamography

• Pap smear

TertiaryReducing

complications (rehabilitation)

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.

Screening vs. Diagnosis

Screening 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

Ideal screening program

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

Quality of primary or secondary prevention (Cheap, effective, safe)

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

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

Cervical Cancer-Pap Smear

1. Long preinvasive period

2. Increased morbidity and mortality in invasive period

3. Treatable if early diagnosis

4. PAP smear: Sensitive, low cost, easy to apply, safe

• 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

Cancers suitable for screening

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

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%

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

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 (+)

Sawaya G. N Engl J Med 2009;10.1056/NEJMp0911380

Cervical Cytologic Screening Guidelines from the American College of Obstetricians and Gynecologists, 2009

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

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)

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

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)

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; 360:1310NEJM 2009; 360:1320

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.

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.

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)

Prostate Cancer Screening

• NCCN recommendation– DRE yearly starting at age 40– PSA yearly starting at age 40

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

Hepatocellular Carcinoma

Cirrhosis• Hepatitis B, C• Alcohol• Genetic hemocromatosis• Non-alcoholic

steatohepatitis• Autoimmune hepatitis• Primary biliary cirrhosis

No cirrhosis• Hepatitis B carrier• Non-alcoholic

steatohepatitis

Ultrasonography

Alpha-feto protein (AFP)

Every 6-12 months

Diagnosis rate: %92

False (+): %7.5

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

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.