The important of “ Cancer Screening”

The important of

“ Cancer Screening”

Aumkhae Sookprasert, MD

Medicine department, KKU

Cancer Screening

The most important end points for

cancer screening

Detect early stage case

Reduction in the incidence of advanced

case

Improve overall survival

Decreased overall and

specific mortality

Population based, RCT !

Levels of Evidence in Cancer Screening

Decreased OS, DSMR in a well-performed RCT

Finding of decreased MR in internally controlled trials (but not RCT)

Finding of decreased MR from case cohort or case controlled observational studies

Results of multiple time series studies with or without intervention

Opinion of respected authorities or consensus reports of experts

* Cause-specific mortality is the 1o end point

Potential “Bisases” of Screening

1. Selection bias

Potential “Bisases” of Screening

2. Lead time bias

DeathControl

Screen

Potential “Bisases” of Screening

3. Length bias

Indolent cancer, Pts with old age

“Overdiagnosis”

DeathControl Symptoms

Fast growing

Death rapidly

ScreenSlow growing, favorable prog

Asymptomatic+ Screening

Harmful of Cancer Screening !!

Levels of Evidence in Cancer Screening

Decreased OS, DSMR in a well-performed RCT

Finding of decreased MR in internally controlled trials (but not RCT)

Finding of decreased MR from case cohort or case controlled observational studies

Results of multiple time series studies with or without intervention

Opinion of respected authorities or consensus reports of experts

* Cause-specific mortality is the 1o end point

Characteristic of “Good Cancer Screening test”

High sensitivity High specificity

Especially if it trigger invasive diagnostic procedures !!

Standard Common

Cancer Screening &

Level of Evidence

Breast Cancer

Breast Level of evidence

Comments

Age 40 – 49 yr

-Mammo+/-CBE 1 +RCT done in this subset of women

-BSE 5 RCT show inc biopsy rate without reduction of BC mortal

Age 50 – 69 yr

-Mammo+/-CBE 1 Benefits and harm are more favorable than younger women

-BSE 5 RCT show inc biopsy rate without reduction of BC mortal

Age 70+ yr - Not well represent in RCT, considered health and life expectancy

Breast Cancer :How to screen effectively ?

5040 60

Mortality

Breast Cancer :How to screen effectively ?

5040 60

Mortality

Cervical Cancer

Cervix Level of evidenc

e

Comments

Pap Smear 3 Case control studies support utility of Pap smear, indirect evidence suggest benefit should be obtained by screening 3 yrs after sexual or by age 21 yr

Cervical Cancer :How to screen effectively ?

5040 6021

3 yr

Ovarian Cancer

Ovary Level of evidenc

e

Comments

CA 125

4, 5

Insufficient evidence of benefitPotential of HarmMost organization recommend against screening with both tool in general pop or women with history of affected family member

Transvaginal U/SX

X

Prostate Cancer

Methods Level of evidence

Comments

PSA 5 Overdiagnosis is an issue

RCT are in progress

DRE 5 RCT are in progress

Transrectal

U/S

5 Lack of specificity !!X

X

X

Testicular Cancer Screening!

Method Level of evidence

Comments

Palpation 5 Screening unlikely to benefit, Px success of advancedDisease rarity

X

Colorectal Cancer

Methods Level of eviden

Comments

FOBT 1 Effective for aged >/= 50 yrs

(+ data in RCT)

Sigmoidoscope 3 + data from several case control study, start at age of 50 yrs

Colonoscope 5 No data

DC Barium Ene 5 No data

CT colonograp 5 Sens & specificity vary !

Colorectal Cancer :How to screen effectively ?

5040 60

FOBT

q 3 yrs

Lung Cancer Screening

Method Level of evidence

Comments

CXR -RCT show no benefit for CXR and cytology

Sputum cytology

-

Spiral CT - RCT are in progress

X

X?

Leading cancers in Thailand (estimated), 1996

0 10 20 30 40

Leukaemia

Stomach

Skin & melanoma

Non - Hodgkin lymphoma

Bladder

Prostate

Oral cavity & pharynx

Colon & rectum

Lung

Liver

0 10 20 30

Leukaemia

Skin & melanoma

Thyroid

Oral - cavity & pharynx

Ovary

Colon & rectum

Lung

Liver

Breast

Cervix

ASR (World)ASR (World)

Male Female

37.6

25.9

10.8

6.8

4.8

4.6

4.9

4.2

4.1

3.9

19.5

17.2

16.0

10.0

7.3

5.2

4.8

3.6

3.6

3.5

Tumor registry report 2000 Courtsey from Dr Pisaln Mairiang.

Liver cancers in different regions, 1995-1997

ASR (World) ASR (World)

Male Female

95.7

0 20 40 60 80 100

Songkhla

Bangkok

Khon Kaen

Lampang

Chiang Mai

Thailand

China, Qiding Country

0 20 40 60 80 100

Songkhla

Bangkok

Khon Kaen

Lampang

Chiang Mai

Thailand

Thailand, Khon Kaen

37.6

18.4

28.7

85.0

14.4

5.7

35.4

16.0

7.5

12.4

32.7

3.9

1.4

Tumor registry report 2000 Courtsey from Dr Pisaln Mairiang.

Tumor Registry

Cancer Unit, Khon-kaen

University

Statistical Report2003

Number of cancer cases by type of patients

Type of patients Number of cases

Total No of OPD 439,662

Total No of new patients 43,564

Total No of new malignancies

4,049

5 Leading sites of cancer in both sexes

1. Liver and bile ducts : 1,186 29.3%

2. Bronchus and Lung : 368 9.1 %

3. Cervix uteri : 337 8.3 %

4. Breast : 192 4.7 %

5. Lymph nodes : 184 4.5 %

Hepato-biliary : 39.5%

Bronchus & lung

: 12.6%

Lymph nodes

: 5.2%

Leukemia : 4.6%

Nasopharyngeal

: 3.4%

Hepato-biliary : 39.5%

Cervical : 17%

Breast : 9.6%

Thyroid gland : 6,8%

Bronchus & lung

: 12.6%

HCC & Gastric CA screening

Method Level of evidence

Comments

HCC- APF,U/S

- One RCT in China benefit, but had serious problem and inference to US pop uncertain !

Gastric- Scope

- Good evidence that scope in US pop not dec mortality,Data on higher risk uncetain

X

X

RCT of screening for HCC

Zhang B, Yang B, Tang Z et al. J Cancer Res Clin Oncol 2004

19,200 : 35-59 yr + HBV markers

Chronic hepatitis

RScreen gr

(9757)Control (9443)

Participate (9373)

Not told, No screen

Zhang B, Yang B, Tang Z et al. J Cancer Res Clin Oncol 2004

Screen gr (9757)

19,200 : 35-59 yr + HBV markers

Chronic hepatitis

R

Control (9443)

Participate (9373)

Not told, No screenAFP, U/S

q 6 mo

Recruited

1993 - 1995

End of study at 1997

- At least 5-7 times screening

Screen gr (9757)

19,200 : 35-59 yr + HBV markers

Chronic hepatitis

R

Control (9443)

Participate (9373)

AFP, U/S q 6 mo

Recruited

1993 - 1995

1st screen + HCC

- 17 pts (0.18%)

By the end (1997)

- 69 pts (0.73)

December 1997

- 32 dies from HCC

Not told, No screen

67 pts with HCC

54 dies from HCC

Incidence of HCC between screening & control

279.3 : 100,000

267 : 100,000

(268 : 100,000)

Stage distribution

Stage Screen gr Control gr

Stage I 52 (60.5%) 0

Stage II 12 (13.9%) 25 (37.3%)

Stage III 22 (25.6%) 42 (62.7%)

Small HCC 39 (45.3%) 0

Treatment modality

Treatment Screen gr Control gr

Resection 40 (46.5%) 5 (7.5%)

TACE/PEI 28 (32.6%) 28 (41.8%)

Conservative 18 (20.9% 34 (50.7%)

Disease specific end points : Death from HCC

How can we make a conclusion ?

5035 59

+ HBV

CAH

q 6 Months !

Cholangiocarcinoma (CHCA)

Courtsey from Dr Pisaln Mairiang.

CT SCAN

Courtsey from Dr Pisaln Mairiang.

ERCP

Courtsey from Dr Pisaln Mairiang.

Ultrasonography

Courtsey from Dr Pisaln Mairiang.

Surgery is the only

chance for cure !

Any methods should we used to detect early cancer ?

Etiology

• Infection:Opisthorchis viverrini, Clonorchis sinensis• Inflammatory bowel disease and Primary sclerosing cholangitis• Chemical exposures: Thorium dioxide, rubber and wood industry• Congenital diseases: Choledochal cyst and Caroli disease• Other: Ductal adenoma, biliary papillomatosis and alpha1-antitrysin deficiency

Courtsey from Dr Pisaln Mairiang.

Stool exam

U/S

CT

ERCP

MRCP

Stool exam

Prevalence : 24.5%

Incidence of CHCA in age > 35

= 93 – 317 / 100,000

= 0.0009 – 0.003

With highest prevalence

1 CHCA : 3,333

¼ U/S : 833

With Lowest prevalence

1 CHCA : 111,111

¼ U/S : 27,777

Sriumporn S, Pisani P et al. Trop Med Int Health 2004

No effective screening

for CHCA !!

Conclusion

Mammo,CBE

q 1 yr, >/= 40

Breast

Cervical

PAP q 1 x 3

>/= 21 yrs

AFP,U/S q 6 mo

>/= 35 yrs

HCC (high risk gr)

FOBT q 1 yr

>/= 50 yrs

Colon

Conclusion

AFP,U/S q 6 mo

>/= 35 yrs

HCC (high risk gr)

FOBT q 1 yr

>/= 50 yrs

Colon