Making sense of prostate cancer screening

Transcription

1 Making sense of prostate cancer screening Piotr Czaykowski MD MSc FRCPC Medical Oncology, CancerCare Manitoba University of Manitoba

2 Disclosure of Potential for Conflict of Interest Name of presenter Name of presentation Piotr Czaykowski Making sense of prostate cancer screening FINANCIAL DISCLOSURE Grants/Research Support: None Speaker bureau/honoraria amounts: None Consulting fees: None Other: None

3

4 67% of 46 Canadian responders favored screening 91 written comments submitted: 71% in favor of screening: Many supported screening after personal experience with elevated PSA that led to lifesaving treatment Some felt PSA screening reassured patients that physician was actively performing surveillance N Engl J Med 2012; e25(1,2)

5 Screening - definition Secondary prevention In the context of cancer: In the absence of symptoms Identifying a pre-cancerous lesion or early cancer at a potentially curable stage

6 Essentials For Screening Disease incidence is significant Disease affects the quantity or quality of life Disease must have a pre-clinical phase during which treatment reduces morbidity and/or mortality Acceptable methods of treatment Earlier treatment is superior to delayed treatment Rapid, noninvasive, inexpensive tests available for detection in asymptomatic phase Frame and Carlson, J Fam Practice 2: 189, 1975 The overall benefit of screening should outweigh the harm (WHO Screening Criteria)

7 Essentials For Screening Prostate Cancer Disease incidence is significant Disease affects the quantity or quality of life?disease must have a pre-clinical phase during which treatment reduces morbidity and/or mortality?acceptable methods of treatment?earlier treatment is superior to delayed treatment Rapid, noninvasive, inexpensive tests available for detection in asymptomatic phase Frame and Carlson, J Fam Practice 2: 189, 1975?Effective screening tool (Czaykowski criterion)?the overall benefit of screening should outweigh the harm (WHO Screening Criteria)

8 Disease incidence is significant 2009: Incidence 727 cases (4 th overall) Mortality 169 deaths (4 th overall) Cancer in Manitoba: 2009 Annual Statistical Report CancerCare Manitoba Epidemiology and Cancer Registry

9

10 Disease affects quantity or quality of life Canadian Cancer Statistics 2008: Potential years of life lost to prostate cancer in 2004: 33,200 Ranked 3 rd in males Based on projected life expectancy at age of death from prostate cancer

11

12 Epstein et al. JNCI 2012

13 Lifetime Risk of Developing or Dying of Prostate Cancer for a 50 Year Old Man in the United States Lifetime Risk of Risk Risk Ratio Proportional Risk Developing histological cancer 42% Developing clinical cancer 16% Dying of prostate cancer 3.6% Modified from Scardino PT. Urol Clin N Am 1989 and Hum Path 1992; and from CA Cancer J Clin Jan-Feb, 2000.

14 Preclinical phase where intervention is possible 90 Latent prostate cancer by age Percent with latent prostate cancer African-American Caucasian Age Group Autopsy series trauma victims who underwent autopsy within 24 hours of death (N=525) Sakr et al. European Urology 1996; 30:

15 Acceptable methods of treatment at early stage Radical prostatectomy Radical radiotherapy External beam Brachytherapy Active surveillance

16 Prostate Cancer Dilemma Is the profound difference between the incidence and mortality rates due to the beneficial effects of treatment or the benign natural history of the disease? Is cure of prostate cancer possible when it is necessary? Is cure necessary when it is possible? Willet Whitmore, Jr., MD

17 Radical prostatectomy versus observation in PSA-detected prostate cancer P=0.22 P=0.09 Wilt et al. NEJM 2012

18 NB: Only 31 prostate cancer deaths in observation arm, 21 in RP arm PIVOT Trial - 2

19 Radical radiotherapy in PSA-era There are no RCTs comparing RRT (external beam or brachytherapy) to observation or to surgery Typically quoted late adverse effects of radiotherapy: rectal injury (<10%) urinary issues (~10%) fistula (<5%) erectile dysfunction (~30%) Does radiotherapy cure prostate cancer?

20 Active surveillance Definition: In those with good prognosis features, following closely, intervening only if the cancer looks to be a bad actor Klotz Current Oncology 2012

21 Earlier treatment is superior to delayed treatment For patients with aggressive disease (high grade, high PSA), this is possibly true For those with less aggressive disease - randomized trials (START, PROTECT) are currently looking at the question of outcome with active surveillance versus immediate therapy (prostatectomy or radiotherapy) The jury is out

22 Rapid, non-invasive, cheap screening tool: Serine protease Prostate Specific Antigen Secreted only by the prostate Function: lyses the seminal coagulum Very sensitive indicator of the presence of prostatic tissue Readily, rapidly and reproducibly measured in the blood at increasingly diminutive concentrations Inexpensive in the grand scheme of things

23 PSA: An Imperfect Screening Tool PSA is organ, not cancer, specific Significant overlap between BPH and cancer Sensitivity of 70-80% when the PSA is normal (< 4) 20-30% of tumors will be missed with PSA alone Influenced by: Patient Age/Prostate Volume Prostate Cancer Prostatic Inflammation Race/Ethnicity

24 Thompson IM et al. NEJM 2004

25 Issues with Prostate Cancer Screening with PSA 1. False positive I. Anxiety ( PSA-psychosis ) II. Over-investigation harm from further tests 2. False negative I. False reassurance II. Miss chance for cure or meaningful intervention 3. Overdiagnosis I. Overtreat a patient whose prostate cancer would II. never have caused any problems Anxiety

26 Overdiagnosis and Overtreatment Overdiagnosis defined as the estimated number of prostate cancers detected by screening that would not have come to light otherwise, in the patients lifetimes: 23-42% in USA 66% in Europe Overtreatment treatment of overdiagnosed cancers: Extrapolating from patient choices, all comers 70% will choose primary treatment Thus 16-29% of all screen-detected prostate cancers are overtreated Lead Time difference in time between screen detected and clinically detected prostate cancer: years Draisma JNCI 2009 Gulati J Clin Epi 2011

27 Overuse of PSA screening: US Practice 25% of US men aged 85 have yearly PSA ~1/3 of US 70, with projected risk of death 50% within 5 years have yearly PSA ~90% of men with low risk prostate cancer undergo curative therapy Most (80%) have surgery undertaken by lowvolume surgeon Vickers AJ et al Annu Rev Med 2012; 63: 161

28 Effectiveness of PSA Screening: The evidence ERSPC Schröder et al NEJM 2009; 360: 1320 NEJM 2012; 366: 981

29 Primary endpoint

30 2012 Update

31 2012 Update

32

33 PLCO Trial 76,693 men in 10 US Study centres randomized to annual PSA and DRE screening or usual care Problems: Contamination: 52% of control group had PSA measurements

34 Primary endpoint

35 Meta-analysis Djulbegovic BMJ 2010; 341:c4543

36 US Preventive Services Task Force

37 USPSTF

38 USPSTF

39 USPSTF

40

41 Criticism of USPSTF CSS curves from ERSPC and PLCO are only now starting to diverge at > 10 years, NNS and NNT estimates are dropping Screening thus makes most sense for those who are younger and healthier where they are likely to outlive the lead time, and benefit from available treatments (especially if active surveillance adopted) These arguments essentially discount the potential harm of current treatment practices

42 AUA Screening Recommendations

43 Poignant thought Quality of life critical May be better to live 15 years with minimal or no side effects than 18 being impotent/incontinent or having radiation toxicity Local Winnipeg Urologist

44 Take home message for Primary Care Although there may be a benefit, current estimates are that it is not large enough to justify PSA screening in the manner in which it has been performed hitherto, given the risk of overdiagnosis /overtreatment

45 Who should you screen? Those with strong family histories Those who have thought it through, understand the benefits and risks, and want to proceed Maybe younger and healthier patients recognizing that they have the most to lose as well as gain Not the elderly (70 or greater) or infirm Can t really just close the door on this pandora s box counseling remains key

46 What would you do? PSA Conundrums 27 year old has PSA measured as part of a fertility workup. PSA year old with a strong family history of prostate cancer. PSA is normal. Wants a prophylactic radical prostatectomy. 57 year old has urinary obstructive symptoms, pain in back. Firm prostate. PSA 3.5 and stable. 78 year old, feeling well. Your partner does a PSA for the first time while you are away. PSA is 71. True stories