PSA as a Screening Test - AGP' GP's Perspective

Transcription

1 PSA as a Screening Test - AGP' GP's Perspective Chris Del Mar cdelmar@bond.edu.auedu au Member of the RACGP Red Book Committee

2 Background: prostate cancer is serious 9 th ranked cause of disease burden in Australian males 2.7% of the total Australian disability adjusted life-years (DALYs) ie 36,000 (DALYs) cf breast cancer for women: (60,000 DALYs, 4.8%)

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4 Background: PSA test: potential for screening Surge in screening in the USA 35% % 1992 associated with decrease in symptomatic presentation of localised prostate cancer 77% % 1992

5 Australian PSA testing

6 Background: PSA test: potential for screening But mortality from prostate cancer has changed little in 20 years: 0.6/1, /1,

7 Australian prostate cancer Rate per 100, Incidence Mortality Year

8 Background: PSA test: t what is it? protease which breaks down the ejaculate coagulum in mammalian species highly specificity for prostatic tissue useful in identifying prostate tissue in tumours of uncertain origin i problems with identifying early Ca Pr: many benign and malignant disorders normally with age

9 Background: PSA screening: why problems? PSA test Is there Ca Pr? yes no +ve True +ve False +ve -ve False -ve True -ve We have no direct data on Sn and Sp of PSA for screening

10 Background: PSA screening: why problems? No direct data on Sn Sp indirect: total PSA could not be distinguish between 131 men with benign prostate hypertrophy p y 79 with localised prostate cancer suitable for radical prostatectomy Weck kermann 1999

11 Background: PSA screening: why problems? No direct data on Sn Sp Swedish population study linking records of PSAs with a cancer register found that to obtain likelihood ratios <0.1 requires a PSA cut point as low as of 1ng/ml Weck kermann 1999

12 Background: PSA screening: why problems? No direct data on Sn Sp indirect: Sakr 1996

13 Background: PSA screening: why problems? We need a better marker! free-to-total PSA? PSA acceleration?

14 Philella 2013 SR of propsa and phi

15 empirical trials of screening 1999: 2 RCTs published in NEJM Andriole (US) no benefit Schroeder (Europe) slight benefit other (smaller RCTs) preceding other (smaller RCTs) following (Gothenberg) Systematic reviews benefit Cochrane review no benefit BMJ (later) no benefit

16 empirical trials of screening 1999: 2 RCTs published in NEJM Andriole (US) no benefit Schroeder (Europe) slight benefit other (smaller RCTs) preceding p other (smaller RCTs) following (Gothenberg) Systematic reviews Cochrane review no benefit BMJ (later) no benefit Problems with compliance: either... controls being screened; or benefit intervention not being screened

17 empirical trials of screening the most optimistic RCT Hugossen (Gothenberg)

18 Dealing with compliance issues Statistical technique Use the 5 randomised trials of screening for prostate cancer: 1) meta-analysis analysis to combine the data (gives a non-significant RR of 8.6% of Pr Ca deaths); 2) the degree of adherence to the screening protocol; and Glaszio ou ) Adjust the meta-analysis for the degree of adherence to screening that t may have influenced the trials. (gives a non-significant RR of 12% of Pr Ca deaths)

19 Dealing with compliance issues Group Stockholm Quebec Norrkoping 2 8 PLCO ERSPC Combined Person Years follow up Control Screen Prostate Cancer Death Control Screen Relative Risk Reduction (95% Confidence Interval) to to to to to to Adherence (%) Control 100% 93% 100% 54% 100% Screen 100% 24% 100% 85% 82% Compliance Adjusted RRR (95% Confidence Interval) to to to to to to D l M CB Gl i PP Hi t GH W i ht RG H ff TC Sh ld Del Mar CB, Glasziou PP, Hirst GH, Wright RG, Hoffmann TC. Should we screen for prostate cancer? A re-examination of the evidence. Med J Aust 2013;198:525-7

20 Summary of benefits of screening uncertain disputed may reduce deaths from Pr Ca may increase deaths

21 What about harms from screening? treatment diagnosis Erectile dysfunction most men Incontinence (esp urinary), returns to normal in 75-90% men in 2 years urinary irritation, bowel symptoms feelings of vitality in 10% biopsy can hurt! serious infection (1%) and bleeding (1%) suicide id x 8in week kfollowing Dx CVD event x 11 other psychological harm? lead-time and over-diagnosis

22 lead-time and over-diagnosis lead-time l d ti lead-time clinically detected disease process screen detected onset of disease process screen detected clinically detected death from the disease time

23 lag-time importance: apparent increase in survival people affected by the diagnosis more

24 over-diagnosis over-diagnosis i clinically detected screen detected disease process onset of disease process screen detected t d death from any cause time death from the disease

25 over-diagnosis importance people are unnecessarily diagnosed treated

26 prostate cancer controversy Age-adjusted frequency PSA testing in men aged years in USA. (data from Mariotto Cancer 2007;109: ) Draisma J Natl Cancer Inst 2009;101:374-83

27 localised Ca prostate incidence 100% overdiagnosis true incidence prostate cancer Draisma J Natl Cancer Inst 2009;101: % overdiagnosis

28 Local Ca prostate lagtime suggests lead time = 5-7 years; overdiagnosis = 23-42% Draisma J Natl Cancer Inst 2009;101:374-83

29 Imagine screening 1000 men. Moyer VA, on behalf of the US Preventive Services Task Force. Screening for Prostate Cancer: U.S. Preventive Services Task Force Recommendation Statement Ann Intern Med

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