Where are we with PSA screening?

Transcription

1 Where are we with PSA screening?

2 Faculty/Presenter Disclosure Rela%onships with commercial interests: None

3 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

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5 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

6 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

7 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

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10 RISK%GROUP% PSA% STAGE% GLEASON% LOW$ <10$ T1C,$T2a$ 6$ 10620$ T2b$ =7$ >20$ T2c$ 8$ INTERMEDIATE$ HIGH$

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12 Options for Treatment Watchful waiting Active Surveillance Radical Prostatectomy Open Laparoscopic Robotic Radiation External beam Brachy Brachy + External Beam

13 Active Surveillance - Results Klotz 2011

14 Radical Prostatectomy Stephenson et al JCO 2009 overall survival cancer specific survival

15 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!!!!

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17 RP vs RT

18 Cancer Specific Mortality Tewari Group Time RRP RT WW Gleason 8+ 4 years 13.4% 16.8% 43% Albertson High- risk 10 years 10% 20% 30%

19 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 EBRT Brachy Can achieve a cure Able to assess defini;ve pathology, Avoids side effects of radia;on Min ;me off work, min early side effects, Min ;me off work, min early SE, less late ED Surgical morbidity 50% ED rate, 5% Incon;nence Rate Late toxicity to the bladder, Secondary Cancer development, No pathology obtained to guide follow up, PSA can be hard to follow aher due to Severe BPH effects, Prostate Fistulas, Urethral Strictures, PSA bounces, no Pathology

20 The Changing Face of Prostate Cancer % of patients < Risk distribution by year of diagnosis Low Intermediate High Advanced Cooperberg MR, et al. J Urol 2007;178:S14-S19

21 49% Decline in Mortality Prostate cancer mortality per 100,000 men aged years FDA Approves PSA Screening %

22 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..

23 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.

24 Canadian Task Force 2014 CMAJ Oct 27, 2014

25 enhanced survival less suffering with disease progression false positives overdetection overtreatment

26 Level 1 Evidence 2014 Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) European Randomized Study of Screening for Prostate Cancer (ERSPC)

27 Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) 10 U.S. Centers ,693 men usual care vs. annual screening DRE for 4 years, PSA for 6 years Andriole et al. NEJM 360: , 2009 Andriole et al. JNCI 104: , 2012

28 PLCO 13 year follow-up Screened Usual Care # cancers relative risk 1.12 (95% CI 1.07 to 1.17) # deaths relative risk 1.09 (95% CI ) Andriole et al. JNCI 104: , 2012

29 Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) 85% compliance for screening but also 52% in control group! (at least) 40% screened within 3 years prior to entering study Andriole et al. NEJM 360: , 2009

30 European Randomized Study of Screening for Prostate Cancer (ERSPC) 7 European countries 182,000 men age (core group 55-69) screening q 4 yrs vs. no screening median follow-up 13 years Schroeder et al. NEJM 2009;360(13): Schroeder et al. Lancet Aug 7, 2014

31 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): Schroeder et al. Lancet Aug 7, 2014

32 Cumulative Risk of Death from Prostate Cancer Schroeder et al. Lancet Aug 7, 2014

33 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

34 Göteborg Subgroup Hugosson, The Lancet, 2010

35 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

36 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

37 CTFPHC PSA SCREENING SURVIVAL BENEFIT OVER TREATMENT

38 How can we decrease overtreatment? Diagnosis Treatment Prognosis

39 BC GU Tumour Group Position statement 2010 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.

40 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 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 PSAD = PSA density; PSAV = PSA velocity Izawa J, et al. Can Urol Assoc J 2011;5:235-40

41 Cease and desist at age 75? vs. Competing risks: age, co-morbidities, aggressiveness of prostate cancer

42 Risk calculator

43 Risk calculator

44 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

45 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