Download Prostate Cancer Surveillance

Prostate Cancer Surveillance
To screen or NOT to screen?
Jackie Keedy, MD
Primary Care Conference
May 26, 2011
Outline

Introduction cases

US Preventative Services Task Force Guidelines

National Comprehensive Care Network Guidelines

Talking points for discussion with your patient

A little data, including “The New Swedish Study”

Conclusion or Confusion?
Case 1.
52 year old Caucasian man at his PCPs office
getting annual physical
Asks to be screened for prostate cancer
because his father had prostate cancer at age
74
He was found to have a PSA of 4.1 ng/ml
Rechecked one month later5.3 ng/ml
Underwent biopsy, was found to have prostate
cancer  had surgery & radiation
Case 2.
54 year old healthy, athletic Caucasian man
No FH of prostate cancer
Serum PSA done as part of annual physical
PSA elevated, so sent to urology
Underwent transrectal biopsy
Became febrile 1-2 days after bx, 103-104, and
was hospitalized for sepsis
Discharged with 6 weeks of IV antibiotics
Case 3.
55 yo obese African American man
No FH of prostate cancer
DRE indeterminate
PSA 250 ng/ml
Being referred to urology
MKSAP Question
An 80-year-old man is evaluated after a serum prostatespecific antigen (PSA) level of 5.7 ng/mL (5.7 µg/L) was
noted during a community screening program. He has no
symptoms related to the genitourinary system and denies
bone pain, weight loss, or any change in his health status.
The patient has hypertension and hypercholesterolemia and
underwent four-vessel coronary artery bypass graft surgery 5
years ago. His current medications are hydrochlorothiazide,
atenolol, lisinopril, pravastatin, and low-dose aspirin.
On physical examination, the patient is afebrile, blood
pressure is 140/80 mm Hg, and the pulse rate is 72/min and
regular. The lungs are clear, and the abdomen is soft and
nontender. There is trace pedal edema in the lower
extremities.
Which of the following is the most appropriate
next step in management?
A
B
C
D

Bone scan
Repeat PSA
Transrectal prostate biopsy
Observation
Observation, right!
In men age 75 years or older, the U.S.
Preventive Services Task Force found
adequate evidence that the incremental
benefits of treatment for prostate cancer
detected by screening are small to none.
USPSTF Guidelines Prostate Cancer
Summary of Recommendations

The USPSTF concludes that the current
evidence is insufficient to assess the balance of
benefits and harms of prostate cancer
screening in men younger than age 75 years.

The USPSTF recommends against screening
for prostate cancer in men age 75 years or
older.
Harms of Detection and Early Treatment

The USPSTF found convincing evidence that treatment
for prostate cancer detected by screening causes
moderate-to-substantial harms, such as erectile
dysfunction, urinary incontinence, bowel
dysfunction, and death. These harms are
especially important because some men with prostate
cancer who are treated would never have developed
symptoms related to cancer during their lifetime.

There is also adequate evidence that the screening
process produces at least small harms, including pain and
discomfort associated with prostate biopsy and
psychological effects of false-positive test results.
Ok, but what if they have a risk factor?

Older men, African-American men, and men
with a family history of prostate cancer are
at increased risk for diagnosis of and death
from prostate cancer.

Unfortunately, the previously described gaps
in the evidence regarding potential benefits
of screening also apply to these men.
Let’s consider our three men
Case 1.
52 year old healthy Caucasian man, + FH
Case 2.
54 year old healthy young Caucasian man, - FH
Case 3.
55 obese African American man, - FH
According to the USPSTF, we should NOT have screened any of them…
To Screen or NOT to Screen?

American Cancer
Society

American
Urological
Association

The United States
Preventive Services
Task Force

Many European
Cancer Societies
National Comprehensive Cancer Network
www.nccn.org
Suggested “Talking Points” for Discussion:
The Pros and Cons of PSA testing


Prostate cancer is the most common cancer in men (older men)
Accounts for 29% of all malignancies in male patients

Second most common cause of cancer-related deaths in men

218,900 new cases in US each year, about 27,000 deaths
related to prostate cancer annually

Men in the US have a 1 in 6 chance
Talking points

Men who have regular PSA tests have a higher chance of
finding out

Men who do NOT have PSA tests have a lower chance but a
higher probability of having more advanced cancer when
ultimately diagnosed

The PSA test can detect the majority of prostate cancers
earlier than a DRE when a man has no symptoms

African-American men and men with a father, brother, or son
with prostate cancer have a higher risk

Native American and Asian-American men have a
substantially lower risk
More Talking Points

Many prostate cancers grow slowly. Consequently, many men
with prostate cancer may die of something else before their
prostate cancers causes any symptoms
 However, prostate cancers that grow more rapidly can
potentially impact overall survival and quality of life
 Whether a man will die of something else or prostate caner
depends on how aggressive the cancer is, how early it is
detected, how effectively it is treated, as well as age and other
problems
 Most experts believe that in general men over age 75, or even
younger with serious medical problems, have little to gain from
a PSA test
More talking points
(for your 15 minute visit!)

Docs disagree about what level of PSA is high enough to do further
testing (biopsy) to look for prostate CA
 Most docs feel men with PSA levels > 4 should have a biopsy,
others feel levels >2.5
 There is an increasing tendency to focus less on absolute PSA
values and to consider changes in PSA over time
 There is accumulating evidence that men who have a steady rise
in their PSA level are more likely to have cancer, and if the rise is
rapid, the cancer is more likely to be life threatening
 Other factors such has patient age and prostate volume (size of
gland) are also important to consider when deciding who needs a
prostate biopsy
Doc, what’s the biopsy like?

A prostate biopsy is usually performed using local
anesthesia through a probe placed into the rectum
through which a needle is placed. Needle takes
samples
 Usually 10-12 samples taken
 The prostate biopsy, not the PSA test, tells whether
or not a man has prostate cancer
 A prostate biopsy is usually well tolerated and
infrequently causes serious problems such as rectal
or urinary hemorrhage, infection, or urinary infection
Frequency of biopsy complications
with 10 core biopsy

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






Hematospermia
Hematuria > 1 day
Rectal bleeding < 2 days
Prostatitis
Fever> 38.5 C (101.3 F)
Epididymitis
Rectal bleeding > 2 days
(+/- surgical intervention)
Urinary retention
Other complications
(requiring hospitalization)
37.4%
14.5%
2.2%
1.0%
0.8%
0.7%
0.7%
0.2%
0.3%
Well, that sounds like a blast.

A PSA test can be abnormal even when a man does NOT have prostate cancer (false +)
 false + PSA tests can come from other prostate conditions that are not important to
find (unless a man has bothersome urinary symptoms)
 About 1 in 3 men with a high PSA level have prostate cancer
 The higher the PSA level, the more likely a man will be found to have prostate
cancer if a biopsy is performed

A PSA test can also be normal even when a man does have prostate cancer (false -)
 About 1 in 7 men with PSA levels less than 4 have prostate cancer
 The higher a man’s PSA level is across all PSA ranges from zero on up, the more
likely a man is to have prostate cancer. This is true even within the so- called
“normal” range.

Prostate biopsies aren’t perfect tests, either. Prostate biopsies sometimes miss cancer
when it is there.
 Some docs recommend a second set of biopsies if the first set is negative
 Others will follow the PSA level and suggest more biopsies only if the level continues
to go up
We went for it, and we found it.
I guess I should be glad we did it?

Common treatments are surgery to remove the prostate or
radiation treatment to the prostate
 Surgery has a very small risk of death
 Both radiation & surgery can cause problems with urinary leakage in
some men, but risk is higher with surgery
 Both radiation & surgery cause problems with getting and keeping
an erection in many men. The risk is higher with surgery in the short
run, but over the long run, the risk is about the same
 Radiation also has a risk of causing bowel problems in some men
 Some men, especially older men with slow-growing cancers, may
not need treatments like surgery or radiation for their prostate
cancer and can be followed with periodic PSA test and physical
exams (watchful waiting, active surveillance or expectant
management)
Does screening reduce mortality??

It is not clear if screening a man with the PSA lowers his chances of eventually dying
of prostate cancer or helps him live longer

Also not clear if screening a man with the PSA test lowers a man’s chances of
eventually having to deal with complications or prostate cancer (painful spread to
bones), but the lower rates of advanced-stage disease at the time of diagnosis and
the lower rates of prostate cancer deaths suggest that few men many suffer from
advanced disease

As a result, docs disagree over the value of screening men with the PSA test

However, it is well established that screening has been associated with an
unprecedented shift in the stages of prostate cancer at the time of diagnosis

More than 75% of cancers are now detected when they are confined to the prostate
gland, when current therapies are most effective

The actual relationship to PSA testing however remains unknown, but available
evidence suggests that the lower mortality rates may be due, at least in part, to PSA
testing
European Randomized Study of
Screening for Prostate Cancer
ERSPC trial released in 2009: Level 1 evidence of PSA screening

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Initiated in the 1990’s to evaluate the effect of PSA testing on death rates from
prostate cancer
Trial involved 182,000 men between ages of 50-74 in 7 European countries
Random assignment to a group that was offered PSA screening at an average of
once every 4 years OR a control group that did not receive such screening
Death from prostate cancer was primary outcome
Median follow-up of 9 years, the cumulative incidence of prostate cancer was
8.2% in the screening group and 4.8% in the control group
There were 214 prostate cancer deaths in the screening group, and 326 in the
control group
The rate ratio for death from prostate cancer in the screening group, compared to
control group was 0.80 (95% confidence interval 0.65-0.98); adjusted P=0.04
The researchers concluded that PSA-based screening reduced the rate of
death from prostate cancer by 20%
However, they also concluded that this was associated with a high risk of overdiagnosis
Statistically, 1,410 men would need to be screened and 48 men would need to be
treated to prevent one death from prostate cancer
United States Prostate, Lung, Colorectal
and Ovarian Cancer (PLCO) Screening Trial

76,693 men between the ages of 55 and 74

Randomly assigned to annual screening with PSA and DRE or to usual
care

A PSA level above 4.0 ng/mL or an abnormal DRE were indications for
biopsy.

A high proportion of men in the control group underwent PSA testing (52
percent in the sixth year of the study) and over 40 percent of study subjects
had undergone PSA testing within three years before enrolling in the trial.

In contrast to the ERSPC, after seven years of follow-up there was no
reduction in the primary outcome of prostate cancer mortality (50
versus 44 deaths in the screening and control groups, respectively; rate
ratio 1.13, 95% CI 0.75-1.70). Cancer detection in the screening group was
significantly higher than in the control group (2820 versus 2322, rate ratio
1.22, CI 1.16-1.29).
Randomized prostate cancer screening trial:
20 year follow-up
To assess whether screening for prostate cancer reduces prostate cancer
specific mortality.
 All men aged 50-69 in Sweden
 1494 men were randomly allocated to be screened by including every sixth
man from a list of dates of birth. These men were invited to be screened every
third year from 1987 to 1996.
 There were 85 cases (5.7%) of prostate cancer diagnosed in the screened
group and 292 (3.9%) in the control group.
 The risk ratio for death from prostate cancer in the screening group was 1.16
(95% confidence interval 0.78 to 1.73).

In a Cox proportional hazard analysis comparing prostate cancer specific
survival in the control group with that in the screened group, the hazard
ratio for death from prostate cancer was 1.23 (0.94 to 1.62; P=0.13)
 After 20 years of follow-up the rate of death from prostate cancer did not differ
significantly between men in the screening group and those in the control
group.

American Urological Association (AUA)
2011 Annual Scientific Meeting
May 16, 2011 (Washington, DC)
”Single PSA Test Before Age 50 Predicts Long-Term Risk”

20,000 Swedish men

obtained PSA information for 1167 men

men with a PSA value above 1.5 ng/mL between the
ages of 45 and 49 years account for nearly half of the
prostate cancer deaths over the next 30 years or so

Only 10% of the men in the study had such high PSA
values at this relatively young age
Single PSA test, continued

On the basis of a PSA value obtained in a man's 40s,
you can stratify risk

This study shows whom we really need to focus on…
The young men in this top 10% need aggressive
follow-up, such as reminder phone calls for doctors'
appointments, and should have either annual or
biennial PSA tests

In the study, which had a median follow-up of 27 years,
44% of all of the prostate cancer deaths occurred in
this top 10% of men.

In other words, a small proportion of the men
accounted for a lot of the prostate cancer deaths.
Not jumping to new guidelines…but

New data call into question the "typical"
recommendations from professional groups about
PSA testing because the recommendations do
not involve risk stratification.

Risk-stratifying screening has 2 major benefits:
 it will reduce over diagnosis in men at low risk for
prostate cancer death
 it will improve compliance with screening in men who
will benefit the most
Radical Prostatectomy
versus
Watchful Waiting in Early Prostate Cancer
“The New Swedish Study”

Suggests that radical prostatectomy is better
that “watchful waiting” for treatment of young
men with low-risk prostate cancer

Contradicts a US trend toward holding off on
surgery and monitoring men who have lowrisk cancers with “active surveillance”
The New Swedish Study, details

An update of a 2008 report with an additional 3 years of data on
nearly 700 men who volunteered for the trial up to 15 years ago;
all had early-stage prostate cancer at the beginning

The study found 38% fewer prostate cancer deaths among men
randomly assigned to the surgery group versus watchful waiting

Men who had surgery had 41% lower risk of growth spreading
throughout their body, and 66% less risk of growth within prostate

Survival benefits were restricted to men under 65

Surgery saved one life for every seven men who had
prostatectomies (considered favorable!)

Applied to men with tumors considered low risk
Important points to think about

Only 1 of 20 men in the Swedish study had a prostate cancer
diagnosis based on high PSA level

Almost 90 percent had tumors their doctors could feel on DRE

In the US, most prostate cancers are identified by PSA
screening, and less than half have palpable tumors

Many prostate cancers found by PSA are likely to be slow
growing (9 out of 10 prostate cancers in the US are
considered low risk)

“low risk” in Swedish study mean higher-risk than current “low
risk” men diagnosed in the US
Another important point

Watchful waiting does not mean the same thing as
active surveillance

Watchful waiting means we are not going to treat you
know and if you progress clinically, we will treat you
with hormone therapy; not with curative intent

Active surveillance means observing the patient in a
proactive way, with regularly scheduled biopsies. If
there is a sign the cancer is progressing, doctors
currently would treat with intent to cure, using
surgery, radiation or both
Last important point

Both surgical techniques and radiation
therapy technology have improved since
the Swedish study was done

So there is reason to think men followed
with active surveillance and treated
when necessary would fare better than
the “watchful waiting” group in new
study
Clear as Mud

There are advantages and disadvantages to having a PSA test, and there is
no “right” answer about PSA testing for everyone

Each man should make an informed decision about whether the PSA test is
right for him

Screening for and the treatment for prostate cancer must be tailored to the
individual man

As a PCP, most patients will do what you suggest, so figure out your stand

Remember that prostate cancer is the 2nd leading cause of death of men

While you are screening for other cancers, think about whether you want to
screen for prostate cancer
References
Bill-Axelson, A. et al. (2011). Radical Prostatectomy versus Watchful Waiting in Early Prostate Cancer.
N Engl J Med 2011; 364:1708-1717
Knox, R. (2011, May 4). Swedish Study Finds Surgery For Prostate Cancer Better Than Waiting.
Message posted to www.npr.org
MKSAP 15. Hematology and Oncology. American College of Physicians.
Mulcahy, N. Single PSA Test Before Age 50 Predicts Long-Term Risk. Medscape News: Internal
Medicine. American Urological Association (AUA) 2011 Annual Scientific Meeting. Abstract 986.
Presented May 16, 2011.
National Comprehensive Cancer Network. (2011). Prostate Early Detection Practice Guidlines.
Retrieved May 10, 2011, from www.nccn.org
Uptodate.com
USPSTF. (2008). Screening for Prostate Cancer. Retrieved May 20, 2011, from
http://www.uspreventiveservicestaskforce.org/uspstf/uspsprca.htm
Sandblom, G. et al. (2011). Randomized Prostate Cancer Screening Trial: 20 year follow-up. BMJ;
342:d1539