Cancer Screening 경희의대 부속병원 종양혈액내과 조 경 삼

Cancer screening Definition Means of detecting disease early in asymptomatic people with the goal of decreasing morbidity and mortality Screening examinations, tests, or procedures are usually not diagnostic, but indicate that a cancer may be present

Lung cancer screening Chest radiographs Sputum cytology –No reduction in lung cancer mortality NCCN (National Comprehensive Cancer Network) lung cancer screening guideline : clinical trial, spiral CT (ex: I-ELCAP) for high risk persons

기간 : 1993 – 2005 (median: 2001) 대상 : high risk persons –≥ 40 years –History of smoking –Occupational exposure (to asbestos, beryllium, uranium, or radon) –Exposure secondhand smoke Baseline and annual screening

Baseline screening : 31,567 명 –Positive result : 4,186 명 (13%) –Lung cancer : 405 명 + 5 명 Annual screening :27,456 명 –Positive result : 1,460 명 (5%) –Lung cancer : 74 명 Total : lung cancer, 484 명 : Stage I, 412 명 10 year survival rate(stage I) : 88% Surgical resection (stage I): 302 명, 92%

Detection rate Baseline screening : 1.3% Annual screening :0.3% Original I-ELCAP –≥ 60 years –Former or current smoker –Baseline screening :2.7% –Annual screenig :0.6%

Problems Definition of “ high risk ” Systematic case-control observation Lead time biases Overdiagnosis False positive Cost-effectiveness

Cancer screening Definition Means of detecting disease early in asymptomatic people with the goal of decreasing morbidity and mortality Screening examinations, tests, or procedures are usually not diagnostic, but indicate that a cancer may be present

Scientific basis There must be a test or procedure that will detect cancers early There must be evidence that treatment at an earlier stage of disease will result in an improved outcome Decrease in cause-specific mortality childhood neuroblastoma prostate cancer

Assessment of screening tests A randomized, controlled screening trial Internally controlled trials Cohort or case-control analytic observational studies Multiple time series studies Opinions of respected authorities

Evaluation of a screening test Screening Truth(diagnosis) test result Cancer(+) Cancer(-) PositiveTPFP NegativeFNTN Sensitivity = TP/(TP+FN) X 100 Specificity = TN/(TN+FP) X 100 Positive predictive value (PV+) = TP/(TP+FP) X 100 Negative predictive value (PV-) = TN/(TN+FN) x 100

Measures of an improved outcome A decrease in cause-specific mortality Reduction in incidence of advanced stage cancers An increase in survival A shift in stage

Biases of screening tests Lead-time bias : no change in natural history ---- prolonged survival time Length bias : slow-growing less aggressive ---- over diagnosis Selection bias : differ from general population ---- healthy volunteer effect

Cancers suitable for screening Substantial morbidity and mortality High prevalence in a detectable preclinical state Possibility of effective and improved treatment because of early detection Availability of a good screening test with high sensitivity, specificity, low cost, little inconvenience and discomfort: breast, cervix, skin, colon-rectum, prostate

Benefits of cancer screening Improved prognosis for those with screen-detected cancers The possibility of less radical treatment Reassurance for those with negative test results Resource saving

Potential drawbacks of screening Screening intervention itself Further investigation of persons with positive test results Treatment of persons with a true- positive result

Disadvantages of cancer screening Economic and psychological consequences of FP and FN Potential for overdiagnosis Potential carcinogenic effects of screening Unnecessary treatment with side effects

Appropriate cancer screening Early detection of asymptomatic or unrecognized disease By the application of inexpensive tests or examinations In a large number of persons

Detection methods Observation: skin, lip, mouth, larynx, external genitalia, cervix Palpation: Breast, mouth, salivary gland, thyroid, anus, rectum, prostate, testes, ovaries, LN in the neck, axilla, groin, Endoscopy, x-rays, MRI, ultrasound Laboratory tests: pop smear, occult blood test

Screening recommendations(I) Sigmoidoscopy: >50: periodically (USPSTF) Fecal occult blood:>50: every year (USPSTF) DRE: >40: every year (ACS) PSA: >50: every year (ACS) Papanicolaou test:18-65: every 1-3 years Pelvic exam:same as Pap test (ACS) Endometrial tissue sampling: at menopause, obese, estrogen use (ACS)

Screening recommendations(II) Breast self-exam: >20: every month (ACS) Breast clinical-exam:>50: every year (USPSTF) Mammography:50-75: every 1-2 years 40-49: (ACS) Complete skin exam: 20-39: every 3 years (ACS)

Breast Cancer Breast self examination Clinical breast examination Mammography MRI Age : over 50 : 20-30% decrease

Cervical cancer Pappanicolaou smears Sexually active for 3years, or 21 years Interval : 1 to 3 years Over 30 : 3 normal tests : 2-3years Over 70 : no abnormal results for previous 10 years

Colorectal cancer Fecal occult blood tests Digital rectal examination Rigid and flexible sigmoidoscopy Barium contrast studies Colonoscopy

Ovarian cancer Adnexal palpation Transvaginal ultrasound Serum CA-125 Genetic ovarian cancer syndrome

Prostate cancer Digital rectal examination Serum PSA Impotence and urinary incontinence At least 10 years life expectancy

NCCN guidelines for screening ( Guidelines for Detection, Prevention, & Risk Reduction of Cancer Breast Cancer Risk Reduction Breast Cancer Screening and Diagnosis Cervical Cancer Screening Colorectal Cancer Screening Genetic/Familial High-Risk Assessment: Breast and Ovarian Breast and/or Ovarian Genetic Assessment Hereditary Breast and/or Ovarian Cancer Li-Fraumeni Syndrome Cowden Syndrome Prostate Cancer Early Detection

Familial melanomap16INK4 melanoma, pancreatic$ Hereditary breast or ovarianBRCA1 Breast, ovary, others$400-2,000 Hereditary breastBRCA2 Breast, others$400-2,000 Hereditary nonpolyposis colon MSH2, MLH1, PMS2 Colon, uterine, others$400-2,000 Li-Fraumeni syndromep53 Brain, sarcoma, others$ Genetic testing for cancer risk

Genetic testing Individuals who are considering genetic testing for cancer susceptibility should be given the opportunity to consider the physical, social, and legal risks balanced against the potential benefits of genetic testing for cancer risk, including the uncertainties of the state of our knowledge of cancer risk and effective interventions

국내 암환자의 스크리닝 (1) 자궁경부암 : 30 세 -- 2 년 – 자궁질경부 도말세포검사 위암 : 40 세 --2 년 – 위내시경 또는 위장조영술 간암 : B, C, 만성 간질환 -- 6 개월 – 복부초음파, AFP 유방암 : 40 세 년 -- 유방촬영술 대장암 : 50 세 년 – 대장내시경, 조영바륨검사

국내 암환자의 스크리닝 (2) 문제점 종양 표지자 (tumor markers) 대상 : 개인 또는 다수 Cost effectiveness No evidence of studies