1. The important of “ Cancer Screening” Aumkhae Sookprasert, MD Medicine department, KKU

2. Cancer Screening

3. 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 !

4. 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 1 o end point

5. Potential “Bisases” of Screening 1. Selection bias

6. Potential “Bisases” of Screening 2. Lead time bias Death Control Screen

7. Potential “Bisases” of Screening 3. Length bias Indolent cancer, Pts with old age “Overdiagnosis” Death Control Symptoms Fast growing Death rapidly Screen Slow growing, favorable prog Asymptomatic + Screening

8. Harmful of Cancer Screening !!

9. 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 1 o end point

10. Characteristic of “Good Cancer Screening test” High sensitivityHigh specificity Especially if it trigger invasive diagnostic procedures !!

11. Standard Common Cancer Screening & Level of Evidence

12. Breast Cancer BreastLevel of evidence Comments Age 40 – 49 yr -Mammo+/-CBE1 +RCT done in this subset of women -BSE5 RCT show inc biopsy rate without reduction of BC mortal Age 50 – 69 yr -Mammo+/-CBE1 Benefits and harm are more favorable than younger women -BSE5 RCT show inc biopsy rate without reduction of BC mortal Age 70+ yr- Not well represent in RCT, considered health and life expectancy

13. Breast Cancer : How to screen effectively ? 504060  Mortality

14. Breast Cancer : How to screen effectively ? 504060  Mortality

15. Cervical Cancer CervixLevel of evidence Comments Pap Smear3Case 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

16. Cervical Cancer : How to screen effectively ? 504060 21  3 yr

17. Ovarian Cancer OvaryLevel of evidence Comments CA 125 4, 5 Insufficient evidence of benefit Potential of Harm Most organization recommend against screening with both tool in general pop or women with history of affected family member Transvaginal U/S X X

18. Prostate Cancer MethodsLevel of evidence Comments PSA5Overdiagnosis is an issue RCT are in progress DRE5RCT are in progress Transrectal U/S 5Lack of specificity !! X X X

19. Testicular Cancer Screening! MethodLevel of evidence Comments Palpation5Screening unlikely to benefit, Px success of advanced Disease rarity X

20. Colorectal Cancer Methods Level of eviden Comments FOBT1 Effective for aged >/= 50 yrs (+ data in RCT) Sigmoidoscope3 + data from several case control study, start at age of 50 yrs Colonoscope5 No data DC Barium Ene5 No data CT colonograp5 Sens & specificity vary !

21. Colorectal Cancer : How to screen effectively ? 504060 FOBT q 3 yrs

22. Lung Cancer Screening MethodLevel of evidence Comments CXR- RCT show no benefit for CXR and cytology Sputum cytology - Spiral CT-RCT are in progress X X ?

24. Leading cancers in Thailand (estimated), 1996 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 3.5 Tumor registry report 2000 Courtsey from Dr Pisaln Mairiang.

25. Liver cancers in different regions, 1995-1997 ASR (World) Male Female 95.7 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.

26. Tumor Registry Cancer Unit, Khon-kaen University Statistical Report 2003

27. Number of cancer cases by type of patients Type of patientsNumber of cases Total No of OPD439,662 Total No of new patients43,564 Total No of new malignancies4,049

28. 5 Leading sites of cancer in both sexes 1. Liver and bile ducts: 1,18629.3% 2. Bronchus and Lung: 3689.1 % 3. Cervix uteri: 3378.3 % 4. Breast : 1924.7 % 5. Lymph nodes: 1844.5 %

29. Hepato-biliary : 39.5% Bronchus & lung : 12.6% Lymph nodes : 5.2% Leukemia : 4.6% Nasopharyngeal : 3.4%

30. Hepato-biliary : 39.5% Cervical : 17% Breast : 9.6% Thyroid gland : 6,8% Bronchus & lung : 12.6%

31. 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

32. 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 R Screen gr (9757) Control (9443) Participate (9373) Not told, No screen

33. 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 screen AFP, U/S q 6 mo Recruited 1993 - 1995 End of study at 1997 - At least 5-7 times screening

34. Screen gr (9757) 19,200 : 35-59 yr + HBV markers Chronic hepatitis RControl (9443) Participate (9373) AFP, U/S q 6 mo Recruited 1993 - 1995 1 st 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

35. Incidence of HCC between screening & control 279.3 : 100,000 267 : 100,000 (268 : 100,000)

36. Stage distribution StageScreen grControl gr Stage I52 (60.5%)0 Stage II12 (13.9%)25 (37.3%) Stage III22 (25.6%)42 (62.7%) Small HCC39 (45.3%)0

37. Treatment modality TreatmentScreen grControl gr Resection40 (46.5%)5 (7.5%) TACE/PEI28 (32.6%)28 (41.8%) Conservative18 (20.9%34 (50.7%)

38. Disease specific end points : Death from HCC

39. How can we make a conclusion ? 503559 + HBV CAH q 6 Months !

40. Cholangiocarcinoma (CHCA) Courtsey from Dr Pisaln Mairiang.

41. CT SCAN Courtsey from Dr Pisaln Mairiang.

42. ERCP Courtsey from Dr Pisaln Mairiang.

43. Ultrasonography Courtsey from Dr Pisaln Mairiang.

44. Surgery is the only chance for cure ! Any methods should we used to detect early cancer ?

45. 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.

46. Stool exam U/S CT ERCP MRCP

47. 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

48. No effective screening for CHCA !!

49. 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

50. Conclusion AFP,U/S q 6 mo >/= 35 yrs HCC (high risk gr) FOBT q 1 yr >/= 50 yrs Colon