Cancer Screening. Robert L. Robinson, MD, MS. Ambulatory Conference SIU School of Medicine Department of Internal Medicine.

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1 Cancer Screening Robert L. Robinson, MD, MS Ambulatory Conference SIU School of Medicine Department of Internal Medicine March 13, 2003

2 Why screen for cancer? Early diagnosis often has a favorable prognosis Some cancers can be prevented if treated in a premalignant state High cost to individuals and society Leading causes of death 172 billion dollars in health care expenses / year 15+ billion dollars in lost productivity / year

3 Failure to screen Rapidly growing area of medical malpractice 40% of all malpractice claims by some estimates Settlements are larger than in any other type of medical malpractice Law firms that specialize in medical malpractice are aggressively seeking clients Must show that patient was harmed (prognosis worsened) by the delayed diagnosis of cancer. Follow current guidelines, follow up on the tests you order

4 Who makes screening guidelines? United States Preventive Services Task Force

5 The ideal screening test Simple to administer Risk free Low cost Low rate of false positives (1 - sensitivity) Low rate of false negatives (1 specificity) RCT(s) to demonstrate improved outcomes NNS (number needed to screen) low

6 Breast cancer 212,600 cases per year, 40,200 deaths Eight RCTs show 25-30% reduction in mortality for women aged years with mammography 15 year follow-up (4 combined RCTs) for 247,010 women shows a 21% reduction in mortality Cochrane review questions methodology of trials Lancet Oct 20;358(9290): Cochrane Database Syst Rev 2001;(4):CD NNS = for mammography USPSTF Every 1-2 years after age 40 ACS Every year after age 40

7 Breast cancer Other options No consistently demonstrated mortality benefit with clinical breast exam No demonstrated benefit for self exam USPSTF Insufficient evidence for either ACS SBE starting at age 20, CBE Q3 years from 20-39, annually thereafter MR Mammography in trials Consider BRCA1, BRCA2 tests for those with strong family history

8 Cervical cancer 12,200 cases per year, 4,100 deaths HPV associated with higher risk Prevention of cancer by removal of pre-malignant lesions Many cohort, case control, and population based studies show benefit for PAP test No RCTs with PAP test 10-30% False negative rate USPSTF every 3 years ACS annual until age 30, then Q 3 years if no history of abnormal PAP

9 Cervical cancer New Developments HPV typing (further stratify risk) AutoPap, PapNet (reduce false negatives) ThinPrep (improve sensitivity)

10 Prostate cancer 220,900 cases per year, 29,900 deaths Unclear if early diagnosis improves prognosis 15 year untreated survival rate is 81% for localized prostate cancer in Sweden RCTs underway USPSTF Insufficient evidence ACS Annual after age 50 w/psa+dre Start at age for high risk populations ACP-ASIM Discuss risks/benefits

11 Prostate cancer Digital Rectal Exam Reduced risk of death (OR 0.31) due to prostate cancer in a large case control study if positive test followed up with prostate biopsy False positive rate is about 66%

12 Prostate cancer Prostate Specific Antigen 25% of males with benign prostate disease have elevated PSA False positive rate of 36-93% depending on cutoff values Progress reports from a trial underway in Canada show a mortality benefit

13 Colorectal cancer 147,800 Cases per year, 57,100 deaths Long preclinical course (10 years) Prevention by removal of pre-malignant lesions Removal of all detectable polyps during colonoscopy reduces incidence of cancer by 75-90% Improved survival with Dukes stage A

14 Colorectal cancer Fecal Occult Blood Test (FOBT) The test preferred by patients (50-74%) Three RCTs show 16-33% decrease in mortality with FOBT followed by colonoscopy if positive Many false positives 98% NNS = 339 USPSTF, ACS, ACP-ASIM Annual after age 50

15 Colorectal cancer Flexible Sigmoidoscopy Widely available Operator dependent, biopsies possible ~ 1/100,000 risk of death Two case control studies with rigid sigmoidoscopy show a 59-79% decrease in mortality USPSTF Periodic screening ACS Every 5 years (option)

16 Colorectal cancer Colonoscopy Evaluates entire colon, expensive Therapeutic and diagnostic ~ 1/1000 risk of death 6-27% of lesions are missed (Gastroenterolgy :24) No RCTs USPSTF Insufficient evidence ACS, AGA Every 10 years after age 50

17 Colorectal cancer New Developments Virtual colonoscopy CT scan to simulate colonoscopy 15% of scans have false positives RCTs underway Fecal gene detection (k-ras, APC, p53) Sensitivity 93%, specificity 97% Trials in screening populations underway

18 Lung cancer 171,900 cases per year, 157,200 deaths Improved prognosis with early detection Chest x-ray, sputum cytology proven ineffective in RCTs Chest CT for screening under evaluation

19 Skin cancer 58,800 cases per year, 9,800 deaths Prevention by removal of pre-malignant lesions No RCTs or case control studies Total body skin exam (PCP vs. dermatologist) USPSTF No screening ACS Every 3 years from age 20-40, annual after 40 ACOG Every year for females 13 and older

20 False Positives False positive rate = 1 Specificity Low prevalence of disease means that most positive tests are false positives

21 FOBT as an example Number # Screened + Screening Test Colon CA cases Colon CA deaths Control Group 1, Annual FOBT Group 1, Minnesota Colon Cancer Control Study. 46,000 subjects, 12,000 colonoscopies, 13 years of followup, Sensitivity 98%, Specificity 90% NEJM :

22 Mammography as an example Number + Screening Test Biopsies Breast CA cases Breast CA deaths Control Group 1, Annual Mammography 1, Projected data from 10 years of screening. Fletcher et al. Essentials of epidemiology 1996, 3 rd ed Williams and Wilkins.

23 Summary Be prepared to discuss risks/benefits of screening No test is perfect False negatives and positives Screening is effective in reducing mortality for some cancers Screening may prevent the development of some cancers

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