Prostate Cancer Screening Dickon Hayne University of Western Australia
JMG Wilson & G Junger, WHO, 1968 p26-27 In theory, therefore, screening is an admirable method of combating disease, since it should help detect it in its early stages and enable it to be treated adequately before it obtains a firm hold on the community. In practice, there are snags
Prostate Cancer Prostate cancer is a common curable cancer that commonly doesn t require cure Autopsy study (Sakr et al J Urol 1993) 25% 30-39 yr olds, 35% of 40-49 yr olds had evidence of CaP Prostate cancer is the second biggest cause of male cancer related death in Australia
PSA Screening PSA is a serine protease produced by prostatic epithelial cells Organ specific but not cancer specific DRE and PSA combined have increased sensitivity and specificity and PPV for prostate cancer compared to DRE alone [Catalona et al Jurol 1994;151:1283-90] Formalised population based PSA screening has yet to be adopted by any nation Currently recommended by AUA and American Cancer Society for men 50> yrs UK early detection through case finding those who present with LUTS, those who seek a test USANZ recommends PSA at 40 for well informed men who wish to reduce their chance of death from prostate cancer
PSA SCREENING
Tyrol study Natural experiment screened in Tyrol compared to unscreened in the rest of Austria 33% reduction in CaP mortality in Tyrol compared to rest of Austria where free screening and treatment available Updated analysis [Oberaigner et al Int J Public Health] Reduced prostate cancer mortality from 2004-2008 in men >60 (risk ratio 0.7)
US screening study PLCO (Prostate, Lung, Colorectal and Ovarian screening trial) Andriole NEJM 2009 76,693 men Annual PSA and DRE vs. standard care (50:50) Median 11.5 year follow up 2820 cancers in screened vs 2322 in control group 92 deaths vs 82 deaths in control at 10 years Conclusion CaP death rate low and no difference between groups Criticisms 40-50% PSA and DRE testing in control arm Biopsy compliance 50% (86% in ERSPC) 44% in each arm had >1 PSA prior to entry PLCO did not comply with minimum standards for a trial i.e.having sufficient power to demonstrate an effect
European randomised study of screening for CaP (ERSPC) Schroeder NEJM 2009 162387 men randomised PSA every 4 years vs. no screening. Endpoint CaP specific mortality 9 year follow up 8.2% CaP in screened vs. 4.8% non screened 0.8 times fewer deaths from CaP in screened group Need to screen 1410 men and treat 48 cases to prevent 1 death Conclusion PSA screening 20% reduction in death rate but high risk over diagnosis Criticisms Heterogenous group, PSA cut off for biopsy 2.5, 3, 10. interval 2 or 4 or 7 yrs, depending on country Need 10-15 year follow up to see impact of 41% reduction in mets in screened arm ¾ TRUS biopsies were negative
Swedish (Goteborg) study Lancet Oncology 2010;11:725-32 Due to different legal regulations in Sweden all men could be randomised without informed consent on one day in 1994 20,000 men (10,000 each group) PSA and DRE every 2 years vs. control 14 yr follow up 1138 screened vs 718 non screened cancers 44% risk reduction in CaP mortality at 14 years Need to screen 293 men and treat 12 men to avert 1 CaP death Criticisms - PSA 2.5 for biopsy 93% men underwent biopsy if triggered by PSA
Characteristics and methodological quality of randomised controlled trials of screening for prostate cancer
Effects of screening on diagnosis of prostate cancer
Effects of screening on all cause mortality and death from prostate cancer Currently no proof that PSA screening reduces mortality from CaP
Cochrane Systematic review -Ilic et al BJUI Int 2011 107:882-91 Identified 5 trials Serious methodological flaws in 3 Increased diagnosis of prostate cancer No difference in prostate cancer mortality
USA Preventive Services Taskforce (USPTSF) Reviewed same evidence as previous metaanalyses Acknowledged outcomes of ERSPC and Goteborg Concluded PSA screening resulted in a small or no difference in prostate cancer-specific mortality at 10 years and is associated with harms related to subsequent evaluation and treatment some of which may be unnecessary Recommends against PSA driven screening has provoked heavy debate and criticism
Conclusions PSA screening is effective in reducing the relative risk of prostate cancer death PSA screening helps to diagnose prostate cancer at an earlier stage but at the risk of over treatment and downstream adverse effects that currently cannot be precisely quantified (Responsible use of active surveillance in management of low risk prostate cancer may mitigate against the adverse affects of over diagnosis of prostate cancer)
What should we actually do? On basis of these findings, population/mass screening remains controversial Opportunistic screening for well informed man may be useful. What age? What interval between PSA and DRE? PSA at 40 < 1ng/ml screening interval 8 years (Schroeder 2005 from ERSPC study). PSA at 75 < 3ng/ml no need for further PSA checks as risk of dying from CaP very low (Carter 2008).
Melbourne Consensus Statement
PSA testing +/- DRE P DO I REALLY NEED THIS TEST OR PROCEDURE? Reduces you risk of dying from prostate cancer but won t necessarily make you live longer More relevany WHAT ARE THE RISKS? PSA test is safe May lead to prostate biopsy (has risks) and risks of overtreatment ARE THERE SIMPLER, SAFER OPTIONS? No WHAT HAPPENS IF I DON T DO ANYTHING? You may miss an opportunity to reduce you chance of dying from prostate cancer You may save yourself the morbidity of overtreatment of prostate cancer WHAT ARE THE COSTS? Financial costs to individual small Costs of population based screening are significant ( to society)
40 year old male DO I REALLY NEED THIS TEST OR PROCEDURE? WHAT ARE THE RISKS? ARE THERESIMPLER, SAFEROPTIONS? WHAT HAPPENS IF I DON TDO ANYTHING? WHAT ARE THE COSTS?
40 year old male (who drinks, smokes and doesn t wear a seatbelt) DO I REALLY NEED THIS TEST OR PROCEDURE? WHAT ARE THE RISKS? ARE THERE SIMPLER, SAFER OPTIONS? WHAT HAPPENS IF I DON T DO ANYTHING? WHAT ARE THE COSTS?
75 year old male (or anyone <7 year life expectancy) DO I REALLY NEED THIS TEST OR PROCEDURE? WHAT ARE THE RISKS? ARE THERE SIMPLER, SAFER OPTIONS? WHAT HAPPENS IF I DON TDO ANYTHING? WHAT ARE THE COSTS?
Male any age with LUTS Men with LUTS require: History (IPSS) Examination including DRE FFR &PVR if available or renal USS MSU PSA This is not PSA screening but the appropriate assessment of a man presenting with LUTS