Prostate Screening in 2009: New Findings and New Questions

Prostate Screening in 2009:New Findings and New

Questions

Durado Brooks, MD, MPH

Director, Prostate and Colorectal Cancer

Screening Recommendations

ACS Screening Guidelines - Process

All American Cancer Society cancer prevention

ACS Screening Recommendations

Prostate Cancer Early Detection Guidelines

Men age 50 and over with at least a 10 year life expectancy should receive information regarding possible benefits and limitations of finding and treating prostate cancer early, and should be offered both the PSA blood test and digital rectal exam annually

Men in high risk groups (African Americans, men with close family members---fathers, brothers, or sons---who have had prostate cancer diagnosed at a young age) should be informed of the benefits and limitations of testing and be offered testing starting at age 45

Testing Controversy

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Types of Tests

Diagnostic Tests - Tests done because of an identified problem (disease is suspected)

Screening Tests -Test done on people who have no symptoms of disease

There is widespread agreement on the use of diagnostic tests for prostate cancer

Screening for prostate cancer is much more controversial

What are Tests for Prostate Cancer?

Key Questions

Does screening extend men’s lives (are there benefits)?

Does screening lead to health problems (are there harms)?

Do the benefits outweigh the harms?

Does screening for Prostate Cancer save lives?

Changes in the PSA Era

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Tyrol, Austria

42% mortality reduction

Olmstead County, Minnesota

22% mortality reduction

SEER

Decreased mortality in white men

Department of Defense

Increased early stage disease


Five-year Relative Survival (%)* during Three Time Periods By Cancer Site

*5-year relative survival rates based on follow up of patients through 2003. †Recent changes in classification of ovarian cancer have affected 1996-2002 survival rates.Source: Surveillance, Epidemiology, and End Results Program, 1975-2003, Division of Cancer Control andPopulation Sciences, National Cancer Institute, 2006.

Site 1975-1977 1984-1986 1996-2002•All sites 50 53 66

•Breast (female) 75 79 89

•Colon 51 59 65

•Leukemia 35 42 49

•Lung and bronchus 13 13 16

•Melanoma 82 86 92

•Non-Hodgkin lymphoma 48 53 63

•Ovary 37 40 45

•Pancreas 2 3 5

•Prostate 69 76 100

•Rectum 49 57 66

•Urinary bladder 73 78 82

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Prostate cancer death rates have fallen during the PSA era, but it is not clear this is primarily due to screening

Other possible reasons for this decline: Disease is found earlier because of

increased awareness

utilization of diagnostic PSA testing

Improved treatments


Limitations of screening

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False negative results

False positive results

Overdiagnosis



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False negative results� PSA and DRE “normal”, but cancer is

present� May lead to false reassurance, delayed

diagnosis

Research has shown that no cut-off value of PSA is completely reliable to rule-out cancer� Prostate Cancer Prevention Trial end of

study biopsies found cancer in some men with PSA less than 1.0 ng/ml


Population Screening with PSA

4.0+

PSA 4+ 7.6%Positive biopsy 25%High grade 19%

Screen 10,000 Men

PSA 4+ 760Cancer 190High grade 36

PSA <4 9240Cancer 1386 High grade 208

“Normal PSA” 92.4% Positive biopsy 15%High grade 15%

<4.0

PSASEER, PCAW, Prostate Cancer Prevention Trial Data


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PSA and/or DRE abnormal, but no cancer found

Can lead to worry, additional tests, and increased costs


Limitations of Prostate Cancer tests

Age (in years)

# With PSA >4.0

# With Cancer

# False Positives

50s 5 1–2 3–4

60s 15 3–5 10–12

70s 27 9 18

If 100 men in each age group are tested:


False Positives = high PSA, but no cancer


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Overdiagnosis

Some (many?) cancers found by screening grow very slowly and will never cause problems


Risk of Prostate Cancer Diagnosis by Age and by Race/Ethnicity

Risk during the next 15 years (per 1000 men )

Race/Ethnicity At age 50 At age 65

All 50 117

African American

White

76

44

163

113

American Indian & Alaska Native

14 35

Asian & Pacific Islanders

18 84

Hispanic 29 94

Risk of Death From Prostate Cancer by Age and by Race/Ethnicity

Risk during the next 15 years (per 1,000 men)

Race/Ethnicity At age 50 At age 65

All 2 16

African American

5 34

White

American Indian & Alaska Native

2

2

14

9

Asian & Pacific Islanders

1 7

Hispanic 1 12

New Findings in Screening

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Results from 2 major, long-term studies reported this year – their findings conflict

ERSPC (European Randomized Screening for Prostate Cancer)

PLCO (Prostate, Lung, Colon and Ovarian)


ERSPC

• Began in 1991 in seven European countries

• 162,000 men aged 55 to 69 randomized to screening vs usual care

• Median follow-up about nine years

ERSPC

Findings• More cancers detected with screening

– 5990 cancers in screening group– 4307 cancers in control group

• Fewer prostate cancer deaths in screening group– 261 deaths in screening group– 363 deaths in control group

• Conclusion: 20% lower prostate cancer deaths in screening group

ERSPC

• Multiple concerns/questions:– Minimal-to-no participation of men of African origin– Different screening and follow-up protocols

• Different PSA levels and DRE usage• Variable treatment and outcomes (quality questions)

– To prevent one prostate cancer death• 1410 men screened• 48 men treated (with attendant risks, side-effects,

complications)

• Bottom line – Screening every 4 years, with PSA threshold of 3

ng/ml may decrease chance of prostate cancer death• Unclear how this correlates to current U.S. pattern of

annual screening with different PSA “triggers” (2.5 – 4.0 ng/ml)

– High level of overdiagnosis and overtreatment with this approach (although these numbers are likely to go down after longer follow up period)

– Relevance of findings to African American men unclear

PLCO

• Began in 1993, ten U.S. Centers • 73,000 men aged 55 to 74

randomized to screening annually vs routine follow-up

• Median follow-up about ten years

PLCO

Findings • At 7 years, screening found more cases of cancer

– 2,820 prostate cancers in annual screening group– 2332 cases in “usual care” group

• More prostate cancer deaths in screening group– 7 years: 50 deaths among annually screened compared

with 44 in usual care group– 10 years: 92 deaths in annually screened vs 82 in usual

care

• Conclusion – No mortality benefit with screening– Prostate cancer deaths similar in both groups– Overall death rate slightly higher in screened (not

statistically significant)

PLCO

• Questions/concerns with study– 44% of men had at least one PSA test prior to study

• May have excluded more aggressive prevalent cancers• Selectively included men with prostate cancers not

detected by PSA screening (bias against showing a screening effect)

– Many men in the “usual care” group were screened during the course of the study

• Initially powered for 20% contamination, later revised to 38%

• PSA screening in control group : 40% first year; 52% by year 6

– Less than half of those with a positive screen result had a biopsy

– Insufficient African American participation (< 5%) to allow specific analysis of outcomes in this group

• Bottom line – no difference in death rates at 10 years between intensively screened and less-intensively screened men

Relevance of these findings to African American men is unclear

Treatment Options

New Findings in Treatment

JAMA, September 2009

Watchful Waiting

Study published September 2009• 14,500 men aged 65 + with localized prostate

cancer • No active treatment for at least 6 mos following

prostate cancer diagnosis• At 10 years, 9% of men had died of prostate

cancer– 1017 men died of prostate cancer– 5721 men died of other causes– 7420 men still alive

Approximately 11% African Americans in study population, but authors did not report findings separately for this group

• PSA screening detects cancers earlier.

• Treating PSA-detected cancers may be more effective, but this is uncertain.

• PSA may contribute to the declining death rate but the extent is unclear

• False positives are common.

• Overdiagnosis and overtreatment is a problem, but magnitude is uncertain.

• Treatment-related side effects are fairly common.

Potential Benefits

Summary

Potential Harms

Bottom line: Uncertainty about degree of benefits and magnitude of harms

Screening Recommendations

Current ACS Screening Guidelines

Men age 50 and over with at least a 10 year life expectancy should receive information regarding possible benefits and limitations of finding and treating prostate cancer early, and should be offered both the PSA blood test and digital rectal exam annually

Men in high risk groups (African Americans, men with close family members---fathers, brothers, or sons---who have had prostate cancer diagnosed at a young age) should be informed of the benefits and limitations of testing and be offered testing starting at age 45

Thank You!

Documents

Prostate Screening in 2009: New Findings and New Questions