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Where are we with PSA screening?
Faculty/Presenter Disclosure
• Rela%onships with commercial interests: – None
Disclosure of Commercial Support • This program has received no financial support. • This program has received no in-‐kind support from.
• Poten%al for conflict(s) of interest: – None
THE GOALS OF CANCER SCREENING
‘Detect a cancer at an early stage when it is treatable and curable’
Devita, 6th Edition, Chapter 25, Rimer, Schildkraut &Hiatt
#1 CANCER IN MEN (1/7), #3 CAUSE OF CANCER DEATH (1/27) >50 yr 40% have Prostate cancer on Autopsy
Prostate Specific An;gen
• Liquefac;on of Semen • Leaks into circula;on when there is disrup;on of the glandular architecture
• PCa doesn’t make more PSA, it just leaks out more – BPH, Prosta;;s, Urethral instrumenta;on, PCa, Bx
PSA
• Normal <4.0 ng/ml • PSA Velocity:
• if 4-10: 0.75ng/ml/yr • if <4: 0.4ng/ml/yr
• PSA Density: >0.15ng/ml (based on TRUS) • Free/Total: <10% = Inc Sp
RISK%GROUP% PSA% STAGE% GLEASON%
LOW$ <10$ T1C,$T2a$ ≤6$INTERMEDIATE$ 10620$ T2b$ =7$HIGH$ >20$ ≥T2c$ ≥8$
Options for Treatment • Watchful waiting • Active Surveillance • Radical Prostatectomy
– Open – Laparoscopic – Robotic
• Radiation – External beam – Brachy – Brachy + External Beam
Active Surveillance - Results
Klotz 2011
Radical Prostatectomy
overall survival cancer specific survival St
ephe
nson
et a
l JCO
200
9
Radical Prostatectomy • Old fashioned (= standard of care)
– “Radical Retropubic Prostatectomy” (RRP)
• The New Wave – “Robo;c Assisted Laparoscopic Prostatectomy” (RALP)
• Why the change? – Tradi;onally a technically challenging opera;on
• Significant func;onal impairment if done poorly
– Tradi;onally associated with high blood loss – Urologists with new tools want to make their name – Marke;ng $$$$ Marke;ng $$$$ Marke;ng !!!!
RP vs RT
Cancer Specific Mortality
Group Time RRP RT WW Tewari Gleason
8+ 4 years 13.4% 16.8% 43%
Albertson
High-‐risk 10 years 10% 20% 30%
TREATMENT PROS CONS
WATCHING No Treatment related side effects Pain and suffering from metasta;c disease
Ac;ve Surveillance
Limit overtreatment of low risk disease
May miss the window for Cure
RRP Can achieve a cure Able to assess defini;ve pathology, Avoids side effects of radia;on
Surgical morbidity 50% ED rate, 5% Incon;nence
Rate
EBRT Min ;me off work, min early side effects,
Late toxicity to the bladder, Secondary Cancer development, No pathology obtained to guide follow up, PSA can be hard to
follow aher due to
Brachy Min ;me off work, min early SE, less late ED
Severe BPH effects, Prostate Fistulas, Urethral Strictures, PSA
bounces, no Pathology
The Changing Face of Prostate Cancer
Cooperberg MR, et al. J Urol 2007;178:S14-S19
23.8 26.2 31.5
45.8 47.4 45.0
13.1
24.0 23.7
23.5 27.2 29.9
38.5
39.2 38.4
28.0 23.0 23.2 24.6
10.7 6.4 2.7 2.4 2.0
0
20
40
60
80
100
<1990 1990–94 1995–99 2000–01 2002–03 2004–07
Low
% o
f pat
ient
s
Risk distribution by year of diagnosis
Intermediate High Advanced
49% Decline in Mortality
Prostate cancer mortality per 100,000 men
aged 50-84 years
FDA Approves PSA Screening
1975 1986 1991 2009
100 80
60
40
20
0
49%
Probability of eventually developing or dying of prostate cancer by PSA at age 60
Mid-life PSA levels strongly predict long-term risk of prostate cancer morbidity.
Vickers A, Cronin A, Björk T, Manjer J, Dahlin A, Bjartell A, Scardino P, Ulmert D and Lilja H. BMJ 2010; Sep 14;341:c4521. .
US Preventive Services Task Force 2012
¡ “recommends against PSA-based screening for prostate cancer”
¡ the benefits of prostate cancer screening do not outweigh the harms of diagnosis and treatment of prostate cancer
¡ grade D recommendation: ¡ “There is moderate or high certainty that the service has
no bet benefit or that the harms outweigh the benefits.”
Canadian Task Force 2014
CMAJ Oct 27, 2014
¡ enhanced survival
¡ less suffering with disease progression
¨ false positives ¨ overdetection
¨ overtreatment
Level 1 Evidence 2014
Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO)
European Randomized Study of Screening for Prostate Cancer (ERSPC)
Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO)
¡ 10 U.S. Centers
¡ 1993-2001
¡ 76,693 men
¡ “usual care” vs. annual screening ¡ DRE for 4 years, PSA for 6 years
Andriole et al. NEJM 360:1310-19, 2009 Andriole et al. JNCI 104:125-132, 2012
PLCO – 13 year follow-up
Screened Usual Care
# cancers 4250 3815
relative risk 1.12 (95% CI 1.07 to 1.17)
# deaths 158 145
relative risk 1.09 (95% CI 0.87-1.36)
Andriole et al. JNCI 104:125-132, 2012
¡ 85% compliance for screening....
¡ .... but also 52% in control group! (at least)
¡ 40% screened within 3 years prior to entering study
Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO)
Andriole et al. NEJM 360:1310-19, 2009
European Randomized Study of Screening for Prostate Cancer (ERSPC)
¡ 7 European countries
¡ 182,000 men
¡ age 50-74 (core group 55-69)
¡ screening q 4 yrs vs. no screening
¡ median follow-up 13 years
Schroeder et al. NEJM 2009;360(13):1320-1328 Schroeder et al. Lancet Aug 7, 2014
ERSPC - Results ¡ 82% of screening group underwent screening
¡ incidence of prostate cancer ¡ screened: 9.55 cases/1000 person years (n=7408)
(evidence for overdetection; ratio 1.57)
¡ control: 6.23 cases/1000 person years (n=6107)
¡ risk of death from prostate cancer: ¡ 21% relative reduction in screened group (355 vs. 545)
¡ absolute risk reduction 1.28 deaths per 1000 men
¡ therefore number needed to screen 781
¡ number needed to detect to save one life: 27
Schroeder et al. NEJM 2009;360(13):1320-1328 Schroeder et al. Lancet Aug 7, 2014
Cumulative Risk of Death from Prostate Cancer
Schroeder et al. Lancet Aug 7, 2014
Göteborg Subgroup ¡ 10,000 men randomized to screening +
10,000 matched controls in population
¡ mean follow-up 14 years
¡ 44% relative reduction in rate of death from prostate cancer in screened group versus control
¡ to save one death from prostate cancer: ¡ number needed to screen: 273
¡ number needed to diagnose: 12
Hugosson, The Lancet, 2010
Göteborg Subgroup
Hugosson, The Lancet, 2010
Why USTFPS Grade D? ¡ mixes ERSPC, PLCO and prior smaller studies
together as equivalent and came to conclusion that screening has no or only small benefit with respect to prostate cancer specific survival
¡ carefully analyzed harm incurred by screening: ¡ false positive tests with unnecessary evaluation ¡ over-diagnosis ¡ adverse effects of treatment
Criticism of Task Force ¡ no prostate cancer expertise on task force
¡ Over-estimation of harm
¡ many studies showing fewer adverse effects ignored
¡ Canadian context: active surveillance
¡ Under-estimation of benefit
¡ mixed poor trials indiscriminately with ERSPC
¡ did not consider living with metastatic disease
¡ no consideration of time of follow-up
¡ no screening trial will ever show overall survival benefit
CTFPHC
PSA SCREENING
SURVIVAL BENEFIT
OVER TREATMENT
How can we decrease overtreatment?
Prognosis
Diagnosis Treatment
BC GU Tumour Group ¡ The Genitourinary Cancer Tumour Group of the BC Cancer Agency and the
Vancouver Prostate Centre are recommending PSA testing for asymptomatic men who are well informed and wish to pursue early diagnosis of prostate cancer.
¡ There is evidence from randomized controlled trials that mortality decreases with PSA screening for the early detection of prostate cancer and its treatment.
¡ The decision to use PSA for the early detection of prostate cancer should be individualized. Patients should be informed of the known risks and benefits of early detection of prostate cancer with PSA testing.
¡ Early detection of prostate cancer should be linked to a treatment algorithm that includes discussion and prioritization of active surveillance for men with low risk prostate cancer.
Position statement 2010
Canadian Prostate Cancer Screening Guidelines ¡ Offer screening to healthy men age 50 with ≥ 10-year life expectancy ¡ Age 40 years if family history of PCa or African descent ¡ Consider baseline PSA between ages 40–50 as potential marker of
future risk and need for screening
¡ Annual screening is standard, but studies suggest that every 2–4 years is beneficial
¡ Initial screening should include DRE and PSA ¡ PSAV, PSAD, and PSA free:total may improve sensitivity and
specificity
¡ PSA ≥ 4.0 ng/mL = increased risk of PCa ¡ TRUS-guided biopsy required to obtain Dx
Izawa J, et al. Can Urol Assoc J 2011;5:235-40 PSAD = PSA density; PSAV = PSA velocity
Cease and desist at age 75?
Competing risks: age, co-morbidities, aggressiveness of prostate cancer
vs.
Risk calculator http:www.compass.fhcrc.org/edrnnci/bin/calculator/main.asp
Risk calculator http:www.compass.fhcrc.org/edrnnci/bin/calculator/main.asp
CaP Screening Summary
¡ discuss risks and benefits of screening with patient
¡ do not screen if <10 yr life expectancy
¡ individualized patient decision
¡ consider multiple factors rather than just one PSA threshold
Take Home Message about screening
¡ Prostate cancer screening is worthwhile, but:
¡ not every man needs annual PSA
¡ not every elevated PSA needs a biopsy
¡ not every positive biopsy needs treatment
¡ not every treatment results in impotence or incontinence