Cancer

Screening
THANONGSAK CHAOJIN MD.


 What is Cancer
Screening?
A test performed on
asymptomatic individuals
that allows for early
detection, therapeutic
intervention, and decreased
mortality from the disease
Positive result on screening
test often leads to further
Outline
Defenition of cancer screening
Principle of screening test
Bias of screening test
Recommendation of cancer screening
Outline
Defenition of cancer screening
To screen an asymptomatic population to
identify cancer at an earlier stage
Lead to a reduction in mortality from the
disease
Screening is generally not diagnostic test
Screening test If positive >> Diagnostic test
Principle of Cancer screening
Important public health problem in terms
of its frequency and/or severity
Opportunity for early detection >
detectable preclinical phase
Effective treatment can alter the natural
history of the disease ( cause specific
mortality )
Easy, safe and cheap
Bias of screening test
Factors may cause survival times to look
like they are getting better when they are
not
Lead time bias
Length time bias
Overdiagnosis
Selection bias
Length time bias
Onset > early diagnosis >>>>>> Death
Onset >>>>>>>> Symptom>>> Death




Lead Time Bias
Length-time bias
Variability in cancer progression rates
Greater probability of detecting a slower
growing cancer
Slower growing cancers have better
prognosis
Screening will identify cases at a lower
risk of death
Overdiagnosis
Detection of cancer not have progressed to
become symptomatic in the person lifetime
Selection Bias
Participants in cancer screening are
usually different from those who are not
High risk for disease, more health
conscious, have access to better health
care.
6 Common Cancers in
Thailand
Breast Cancer

Colorectal Cancer

Lung and bronchus Cancer

Cervical Cancer

Prostate Cancer

Hepatocellular Carcinoma + Cholangiocarcinoma

Symptoms of cancer






2 ()
2


Symptoms of cancer


1. 0.5
2.

3.
4.






 Events and Strategies in
Cancer Medicine
Situations Interventions
Normal host Cancer prevention

Subclinical disease Screening

Early disease Early Dx & Curative Rx

Advanced cancer Palliative treatment

"

"
 Levels of Cancer
Prevention
Primary prevention

Identification and modification of etiologic factor in environment

Promoting healthy life style
Immunization

Secondary prevention

Early detection of cancer and premalignant lesion to enhance cure

(cancer screening)

Tertiary prevention

Treatment of cancer to avoid recurrence and limit disability

Levels of Cancer
Prevention
Major (Modifiable) Risk
Factors of Cancer
Diet and nutrition

Tobacco

Infection

Occupational & environmental exposure

chemicals, sunlight, air & water pollution

Physical activity

Alcohol
Gr oup of cancer
scr eeni ng
2

-


,

-


hepatocellular carcinoma



Prin ciples of
Screenin g
W orld H ealth
organization,W H O




1.The disease
Important or condi
= Significant tion shoul
Morbidity d be an
/ Mortality
im portant problem

 Prin ciples of
Screenin g
2.

3.







 Prin ciples of
Screenin g
4.



H igh sensitivity (few false negatives)
H igh specificity (few false positives)
G oalis reduced cancer-related m ortality,
not just early case detection

5.
(standard treatm ent)

Symptoms of cancer





10



5

Factor associated with cancer













Factor associated with cancer
10




steroid






Factor associated with cancer

4

Breast Cancer
Screening
Breast Cancer
Screening
Clinical breast
examination (CBE)
Breast self-
examination (BSE)
Mammogram
Breast Cancer
Screening
C lin ical b reast exam
in atio n (C B E)
Breast cancer related m ortality w as
reduced equally in C BE w hen
com pared w ith C BE and
m am m ogram (C anadian N ational
Breast C ancer Study)

B reast self-exam in atio n (B SE)

C hinese RC T in Shanghaifactory
w orkers
BSE instruction & reinforcem ent
N o benefit after 11 years (JN C I
2002)
 Mammogram
Increases
incidence of breast cancer
& Dx of non-invasive cancer/
premalignant lesions Overdiagnosis
???

Strong evidence of benefits in aged >

50
Meta-analysis RR reduction in
BRCA mortality 34%
 M RI Breast
MRI is not currently recommended
for screening w om en at average
risk for breast cancer
The low er specificity of M RI is
a concern, since this could lead
to increased num bers of follow -
up procedures
For high risk w om en, M RI
screening has been recommended in
BRCA1 and BRCA2 m utations
Wom en w ith a strong fam ily
history of breast or ovarian
 Screen in g B reast C an cer
The A m erican C an cer So ciety 2007
Breast self-examination (BSE)
Women > 20 yrs old should be told
about the benefits and limitations of
BSE.
Clinical breast examination (CBE)
Women in their 20s and 30s, it is
recommended that CBE be part of a
periodic health examination,
preferably at least every 3 years.
Asymptomatic women aged > 40 years
should continue to receive CBE as part
of a periodic health examination,
preferably
Alfred, annually.
Neugut. Epidemiology and prevention. ASCO-SEP Medical
Oncology Self-evaluation Program Thrid Edition 2013.
Colon Cancer
Screening
Col on Cancer
Scr eeni ng
1. Structural tests
Si gmoi doscopy
Col onoscopy
Bari um contrast studi es
CT col onoscopy

2. Fecal Occul t Bl ood Testing (FOBT)

 A denom a to C arcinom a
Pathw ay
Normal Adenoma Cancer

7-10 years

APC K-ras Chrom 18 p53

loss mutation loss loss

Normal Hyper- Early Intermediate Late

Cancer
Epithelium proliferation Adenoma Adenoma Adenoma
 Fecal Occult Blood
Testing (FOBT)
Detects blood (Hb) from
cancers or large polyps
Bleeding is
interm ittent and
increases w ith polyp
size and stage of
cancer
Hem occult
False positives: oralII (guaiac-
iron, aspirin,
NSAIDs, red meat, anticoagulants
based) m ost w idely used
False negatives: vitamin C
and studied FOBT
Inexpensive and easy
Fecal Occult Blood
Testing (FOBT)
A d van tag es
M any RC Ts show ed
m ortality reduction 15-
20% after 8-15 years
Easy
Sensitivity of one-tim e
test for advanced
neoplasm :30% and
increase to 80% w hen
Key Point:
repeated testing
Effectiveness of FOBT
will depend on annual FOBT
testing program
Fl exi bl e Si gmoi doscopy
( Fl ex Si g)
60cm flexible sigmoidoscope can
reach to splenic flexure

Well-designed, case-control
studies have found that
sigmoidoscopy reduces overall
colorectal cancer mortality by
about 33%
Colonoscopy
Diagnostic use after
positive results on FOBT or
flexible sigmoidoscopy
gold standard
Improved sensitive and
specific but higher
complications and costs than
FOBT
Estimated effect of
population screening: could
C o lo n C an cer
Screen in g Strateg ies
One-Stage Screening Two-Stage Screening

Colonoscopy FOBT yearly +/-

DCBE every 5 yrs or

Flexible sigmoidoscopy q 5 yrs

Colonoscopy
Lung Cancer
Screeni ng
Lung Cancer
Screening
Modalities
Chest x-ray

Low-dose CT scan
Cumulative Numbers of Lung Cancers and of Deaths from Lung Cancer.

The National Lung Screening Trial Research Team . N Engl J

Med 2011;365:395-409.
Cervical Cancer
Screening
 Causes of Cervical
Cancer
Multiple sexual partners

Cofactors
Early age of
sexual
Persistent intercourse
Immuno HPV infection
suppression
HIV,
transplant Smoking
 Screening for C ervical
C ancer
Long natural history for
progression from CIN to
invasive cancer
Pap smear is the mainstay
Proven efficacy in reducing
cancer-related mortality
by 80% in multiple
observational studies
Screening Cervical Cancer
The American Cancer Society 2007
Women, aged > 18 years should have Pap
test
Cervical cancer screening should begin
approximately 3 years after a woman
begins having vaginal intercourse, but
no later than 21 years of age.
Screening should be done every year
with conventional Pap tests or every 2
years using liquid-based Pap tests.
Women aged > 30 years, who have had
three normal test results in a row may
get screened every 3 years with
cervical cytology (either conventional
or liquid-based Pap test) alone, or
every Alfred,
3 years with an HPV DNA test
Neugut. Epidemiology and prevention. ASCO-SEP Medical
Oncology Self-evaluation Program Thrid Edition 2013.
Prostate Cancer Screening
Screening Prostate Cancer
Major risk factor is age over 80% are found
in men > 65 years old

Natural history is unknown

Screening methods:
Digital rectal exam (DRE):
Only 1/3 of gland is palpated, low sensitivity/ specificity
No studies proving reduction in mortality
Serum PSA & variations
Serum PSA & Screening Prostate
Cancer
Specific for prostate tissue, but not for prostate
cancer

Abnormal value frequently seen in BPH, prostatitis

PSA > 4 ng/mL is suggestive of malignancy

Sensitivity 70-80%, Specificity 60-70%

Other variation to improve specificity of test

Free PSA = free PSA / total PSA ratio
PSA velocity = change over time of PSA
PSA density = PSA related to prostate volume
Screening Prostate Cancer
The American Cancer Society 2007

Men aged > 50 years.

Digital rectal examination (DRE) and prostate-specific antigen test

(PSA)

The PSA test and the DRE should be offered annually, starting at
age 50 years, for men who have a life expectancy of at least 10
more years

High-risk patients should start screening at age 45

Black men or men with a first-degree relative with prostate
cancer diagnosed at a younger age

Smith RA, et al. CA Cancer J Clin 2006; 56:11-25

 Screening Pro state C ancer;
USPSTF Guidelin es
The evidence is insufficient to recommend
for or against routine screening for prostate
CA using PSA or DRE

Although screening can find CA early, it is

uncertain whether the potential benefits
justify the potential harms

To begin at 50 years old or in men with life

expectancy > 10 years
Hepatocellul ar
Carci noma Screeni ng
Worldwide Incidence of HCC in 2000

Age-adjusted incidence rates of liver cancer per 100,000 (men)

<3.3 <5.6 <9.0 <15.0 <98.9

Bosch FX, et al. Gastroenterology 2004;127:S516

 Hepatocellular Carcinoma (HCC)

Majorrisk factor : chronic viral hepatitis

(HBV or HCV), cirrhosis from any
causes, aflatoxin, alcohol

Incidence 0.5% per year

Screening methods every 6 months

AFP: value > 20 ng/mL as usual cut-off
Abdominal ultrasound

Nostrong evidence that these methods

reduces mortality (Chinese data)
Screen in g H C C (A FP + U /S q
6 m th s)
H ep atitis B carriers
Asian males 40
Asian females 50
Africans over age 20
Cirrhosis
Family history of HCC (mainly Asian and African)

N on -hep atitis B cirrho sis

Hepatitis C
Primary biliary cirrhosis
Alcoholic cirrhosis
Primary hemochromatosis
Alpha 1-antitrypsin deficiency
Non-alcoholic steatohepatitis
Autoimmune hepatitis

American Association for the Study of Liver Diseases (AASLD)

Tum o r M arkers fo r C an cer
Screen in g
Tumor Marker Screen
Prognosis Monitor
Recurrence
Colon CEA No Yes Yes Yes

Ovary CA-125 No No Yes

Yes

Breast Ca-153 No No Yes Yes

Ca-27.29

Prostate PSA Yes Yes Yes Yes

Testicle hCG, AFP No Yes Yes Yes

Hepatoma AFP Yes* No Yes Yes

 Take home message
Cancer Colorectal Breast Lung Cervix

Who All with > 50 y Woman > 40 y High risk 55- Woman with
74 y sexually active
or age > 21 y

How Colonosocpy Mammogram Low dose CT PV + PAP

HPV DNA

How often Every 10 y yearly Yearly for 3 y. Every 3-5 y.

Stop No data As long as > 74 y. Age 65-70

screening good health after regular
normal Pap
 Take home message
Cancer Liver Prostate Lung Cervix

Who All with cirrhosis Male > 50 y High risk 55-74 Woman with
CHB M > 40 y + Life y sexually active
F > 50 y expectancy or age > 21 y
CHC with cirrhosis > 10 y.

How Ultrasound and AFP Digital rectal Low dose CT PV + PAP

exam + PSA HPV DNA

How often Every 6 months yearly Yearly for 3 y. Every 3-5 y.

Stop No data > 74 y. Age 65-70 after

screening regular normal
Pap