AProf Brian Cox Cancer Epidemiologist Dunedin Has PSA

A/Prof Brian Cox Cancer Epidemiologist Dunedin

Has PSA testing reduced prostate cancer mortality in New Zealand? Research Associate Professor Brian Cox Hugh Adam Cancer Epidemiology Unit Department of Preventive and Social Medicine Dunedin School of Medicine University of Otago

Ethics of screening We believe there is an ethical difference between everyday clinical practice and screening. If a patient asks a medical practitioner for help, the doctor does the best possible. The doctor is not responsible for defects in medical knowledge. If, however, the practitioner initiates screening procedures the doctor is in a very different situation. The doctor should, in our view, have conclusive evidence that screening can alter the natural history of disease in a significant proportion of those screened. (From: Cochrane & Holland, 1971)

Meta-analysis of RCTs of prostate screening (Djulbegovic et al BMJ 2010)

5 19 4 5 19 6 5 19 8 6 19 0 6 19 2 6 19 4 6 19 6 6 19 8 7 19 0 7 19 2 7 19 4 7 19 6 7 19 8 8 19 0 8 19 2 8 19 4 8 19 6 8 19 8 9 19 0 9 19 2 9 19 4 9 19 6 9 20 8 0 20 0 0 20 2 0 20 4 0 20 6 08 19 Rate (per 100, 000) Trends in the incidence of prostate cancer 1600 1400 Year 45 -59 60 -69 70 -74 75+ 1200 1000 800 600 400 200 0

Estimated cost of PSA diagnoses From 1990 to 2012 there have been about 19, 390 diagnoses of prostate cancer in New Zealand from PSA testing of asymptomatic men that would not have otherwise occurred. At 2008/2009 prices for treatment*, this was $340 m over 23 years and ~$15 m in 2012. About 850 men a year are diagnosed with prostate cancer by PSA testing who would not otherwise have that diagnosis in their lifetime.

54 58 19 60 19 62 19 64 19 66 19 68 19 70 19 72 19 74 19 76 19 78 19 80 19 82 19 84 19 86 19 88 19 90 19 92 19 94 19 96 19 98 20 00 20 02 20 04 20 06 20 08 19 56 19 19 Rates Mortality 600 Year 45 -59 60 -69 70 -74 75+ 500 400 300 200 100 0

Relative risk 17 16 15 1800 1600 14 1400 13 1200 Registration Mortality 1000 12 800 11 600 400 10 200 9 0 Registration cohort 45 -4 50 9 -5 55 4 -5 60 9 -6 65 4 -6 70 9 -7 75 4 -7 80 9 -8 4 85 + 8 7 Age group (years) 6 Mortality cohort Period of registration Period of mortality 5 4 3 2 1 0 18 1870 1875 1880 1885 1890 1995 1900 1905 1910 1915 1920 1925 1930 1935 1940 1945 1950 1955 1960 1965 1970 1975 1980 1985 1990 2095 2000 05 Age-periodcohort representation of trends in prostate cancer in New Zealand Age effects Median year of birth or first year of time period

Is there an overall benefit of PSA tests in asymptomatic men? Boniol et al (2012) BJU International — from the International Prevention Research Institute and the Urology Service of the Lyon-Sud hospital, Lyon. They have estimated that: Using the results of the ERSPC randomised trial and the Swedish arm, PSA testing produced a loss of years of life. This was primarily due to prostate biopsy rates of 27% and 40% for the ERSPC and Swedish arm, respectively, and they used an estimate of 1 in 500 for the risk of death from complications of biopsy. Treatment mortality of 1 in 200 patients treated for prostate cancer (Walz et al, BJU International 2008)

Estimate of iatrogenic illness and death from PSA testing in New Zealand to 2012 Proportion DXT Surgery treated 50% 70% 30% 9695 6787 2909 proportion affected number afflicted Faecal incontinence 3% 204 Urinary incontinence 5% 339 15% 1018 Number overdiagnosed 19390 Estimated number of biopsies 193900 DXT Impotence Total DXT 1561 Surgery Faecal incontinence 0% 0 Urinary incontinence 10% 291 Impotence 20% 582 Total surgery 873 Overall iatrogenic illness Mortality from treatment Mortality from biopsy Total iatrogenic mortality 2433 1 per 400 24 1 per 2, 000 97 121

Key information for patients, their spouses and their families Despite PSA testing of asymptomatic men (PSA screening) since 1993 in New Zealand, there is little evidence that prostate cancer mortality has declined as a result. It is estimated that since PSA testing began in New Zealand, about 19, 000 men have had a diagnosis of prostate cancer that would not have developed symptoms or threatened their life. Of the 19, 000 men, it is estimated that about 2, 400 have had chronic impotence, chronic urinary incontinence, or chronic faecal incontinence as the result of their treatment.

Screening men for prostate-specific antigen (PSA), the most commonly used tool for detecting prostate cancer, has become a "hugely expensive public health disaster, " says the researcher who discovered PSA in 1970. (March 11, 2010) Richard Ablin, Ph. D, DSc (Hon. ) research professor of immunobiology and pathology at the University of Arizona College of Medicine in Tucson.

U. S. Preventive Services Task Force (USPSTF) gave PSA screening a grade of “D”. This is a recommendation against PSA-based screening for men of any age. The Task Force makes D recommendations when there is at least moderate certainty that the harms of an intervention equal or outweigh the benefits. Mass screening is also a lucrative business. “It is difficult to get a man to understand something, when his salary depends on his not understanding it”. Although the Task Force statement is more pointed than those of other expert organizations, it is not incongruent with those recommendations. Yet, many advocates for prostate cancer screening have ignored the messages of caution of other organizations and continue to encourage screening without caveats.

http: //www. auanet. org/education/guidelines/prostate-cancerdetection. cfm Guideline Statement 1: The Panel recommends against PSA screening in men under age 40 years. (Recommendation; Evidence Strength Grade C) Guideline Statement 2: The Panel does not recommend routine screening in men between ages 40 to 54 years at average risk. (Recommendation; Evidence Strength Grade C) Guideline Statement 3: The Panel strongly recommends shared decisionmaking for men age 55 to 69. (Standard; Evidence Strength Grade B) Guideline Statement 4: To reduce the harms of screening, a routine screening interval of two years or more may be preferred over annual screening in those men who have participated in shared decision-making and decided on screening. (Option; Evidence Strength Grade C) Guideline Statement 5: The Panel does not recommend routine PSA screening in men age 70+ years or any man with less than a 10 to 15 year life expectancy. (Recommendation; Evidence Strength Grade C)