By Nick Tate
Dec. 14, 2021 -- It’s a question that
has divided men’s health experts for years: Should healthy men,
with no symptoms or family history of prostate cancer, get a prostate
specific antigen test and treatment right away if a tumor is found?
Men’s health experts and cancer
specialists say the continuing back-and-forth on PSA testing and
active surveillance has deepened widespread confusion for men with
questions about what to do.
Proponents of routine PSA testing say
it is the best screening tool in oncologists’ arsenals for catching
prostate cancer early, when it is most treatable.
But opponents argue that it prompts
many newly diagnosed men to seek invasive treatments that can cause
impotence and incontinence, although up to 80% have low-risk tumors
that will never be life-threatening. For them, they say, the best
option is “active surveillance,” where doctors monitor patients
closely for signs their cancer is advancing before treating it.
This fall, the influential National
Comprehensive Cancer Network (NCCN) reignited the debate,
recommending active surveillance, surgery, or radiation for men newly
diagnosed with prostate cancer as a result of PSA testing -- giving
equal weight to all three approaches.
After a firestorm of criticism, the
NCCN reversed course and now recommends that “most men” with
low-risk prostate cancer be managed through active surveillance as
the “preferred” first treatment option over surgery and
radiation.
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The updated guidelines also reiterated
the group’s stance against routine PSA testing for most men “as a
general population screening tool due to its well-documented
limitations” and its potential for prompting over-treatment.
Some oncologists even say the debate
has eclipsed the most important point about prostate cancer -- that
each case requires a personalized, patient-centered approach to
testing and care that one-size-fits-all screening guidelines don’t
take into account.
“These guidelines are always changing
back and forth, and I’ve seen a lot of these changes,” says David
Samadi, MD, a urologic oncologist and director of men’s health at
St. Francis Hospital in Roslyn, NY. “But individualized care is the
best way to go.”
He says men should work with their
doctors to determine whether and when to have PSA testing, based on
their unique genetic and biological makeup, age, family history,
overall health, lifestyle, race, ethnic background, and other
factors. Any course of cancer care should be approached in a similar,
patient-centered way, he says.
Otis W. Brawley, MD, a professor of
oncology and epidemiology at Johns Hopkins University, agrees that
PSA testing is an important screening tool, but it should not always
lead to treatment. Men need to weigh the risks and benefits of
testing and understand that most diagnosed with prostate cancer
should not be rushed to surgery, radiation, or other therapies, he
says.
“Given the uncertainty that PSA
testing results in more benefit than harm, a thoughtful and broad
approach to PSA is critical,” Brawley says, citing the current
position of the American Urological Association.
“Patients need to be informed of the
risks and benefits of testing before it’s undertaken. The risks of
over detection and over-treatment should be included in this
discussion.”
Brawley says his own position on PSA
testing has evolved over the past 3 decades, in part because most men
are no longer routinely treated aggressively at the first sign of
cancer.
“I was very much against screening
for prostate cancer, especially in the 1990s,” he says. “Fifteen
years ago, every man who was found to have localized prostate cancer
in the United States, if he was diagnosed on a Tuesday or Wednesday,
he was told it needs to be out of your body by Friday, week after
next, literally.
“Now, there are areas of the United
States where half of all men with screen-detected prostate cancer are
watched and most of those men will never be treated for their
prostate cancer.”
PSA Testing: Pros, Cons
A PSA test measures blood levels of
prostate-specific antigen, which can be high when cancer is present
in the prostate, the walnut-sized gland that produces seminal fluid
and is key to a man’s sexual functioning.
The test was introduced in 1994 to
detect the possible presence of prostate cancer, the second-leading
cause of cancer deaths in American men. A PSA level of less than 4
nanograms per milliliter of blood is considered normal; when it
spikes to 6 or higher in a year’s time, doctors are likely to
suggest a biopsy to check for a tumor.
If prostate cancer is seen on a biopsy,
PSA levels can be used to determine the stage of cancer -- how
advanced it is. Cancers are also assigned a grade -- called a Gleason
score -- that can show how likely it is to spread. Gleason scores of
6 or less are considered “low grade,” 7 is “intermediate,”
and 8 to 10 is “high grade.”
But PSA testing is not foolproof.
Cancer isn’t the only thing that can raise PSA levels.
Inflammation, infection, and an enlarged prostate (common in men over
50) can cause increases in PSA. So it’s not as accurate a cancer
predictor as, say, genetic tests for the BRCA1 and BRCA2 genes
strongly linked to breast cancer (and a very small number of prostate
cancers).
Even when testing turns up a tumor, it
does not indicate whether it’s an aggressive form of cancer that
needs treatment right away or is a slow-growing, low-risk tumor
unlikely to be life-threatening. In fact, autopsy studies have found
that undiagnosed prostate cancer is found in about a third of men
over 70 who die from some other cause.
But there is no question that PSA
testing has helped identify many cancer cases that might otherwise
have not been found in early stages. Research shows:
PSA screening can flag cancer about
6 years earlier than a digital rectal exam and 5-10 years before
symptoms of the disease emerge.
The death rate from prostate cancer
has fallen by more than half since the FDA first approved PSA tests.
Nine in 10 cases in the U.S. are
found while the disease is confined to the gland (or nearby), when
nearly all men with the disease survive 5 or more years.
About 4 out of 5 men with an
elevated PSA who are found on biopsy to have cancer have a low-risk
form of the disease that is unlikely to kill them before something
else does.
Even so, the doubts about PSA testing
have led to widespread debate over who should have it done, at what
age, and how doctors and patients should respond to an elevated
level.
“Not everyone needs to be screened,
not everyone found to have an elevated PSA needs to be biopsied, and
Lord knows that not everyone with prostate cancer needs aggressive
treatment,” said Colorado Springs urologist Henry Rosevear, MD,
writing in Urology Times.
In the face of the uncertainties, men
have to weigh competing and confusing advice on PSA testing and
active surveillance.
For instance:
The American Cancer Society
recommends that men with at least a 10-year life expectancy “make
an informed decision” with their doctor about PSA testing.
Discussions should begin at age 50 for men at “average” risk for
cancer, 45 for those at “high risk” (African Americans and men
with a father, brother, or son diagnosed with the disease before 65),
and 40 for “higher risk” people (with more than one close
relative diagnosed with prostate cancer at an early age).
The National Comprehensive Cancer
Network does not endorse routine screening but advises men 45 to 75
years old to discuss screening risks and benefits with their doctor.
The American Urological Association
recommends that men 55 to 69 years old weigh the risks and benefits
of PSA screening and advises against testing for men under 40, those
between 40 and 54 at “average risk,” and men over age 70 or with
“a life expectancy less than 10-15 years.”
In 2018, the U.S. Preventive
Services Task Force (USPSTF) revised its controversial 2012
recommendation against prostate cancer screening and now advises that
for men ages 55 to 69, “the decision of whether or not to undergo
screening should be individualized.” For men 70 and older, the
USPSTF recommends against PSA testing.
Samadi says tracking PSA levels and
trends over a period of years or decades is far more valuable than a
single isolated test result, when it comes to assessing a man’s
cancer risk and how best to handle it.
“I’m a big proponent of PSA
screening and … I always tell the patients to get a baseline PSA at
the age of 40,” he says. “And if that’s absolutely normal, then
you can repeat it every 2 or 3 years.”
But from the get-go, Samadi says, it’s
important to understand that an elevated PSA test, on its own, does
not necessarily mean any man needs surgery, radiation, or other
treatment right away that can affect his quality of life.
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Brawley agrees, noting that studies
show a prostatectomy (surgery to remove all or part of the prostate)
carries a 40% risk for impotence and/or urinary incontinence and a
0.5% chance of dying from the operation, while pelvic radiation can
lead to bladder and bowel irritation and bleeding.
“A large number of men who are
screened and who are diagnosed with prostate cancer today are going
to be told you have one of the more benign-ish prostate cancers --
yes, it’s malignant, but it’s less aggressive,” he says.
“Therefore, instead of giving you a radical prostatectomy [or]
radiation … we’re going to watch you.”
Advances in Biomarkers, Genetics
In recent years, researchers have been
working to develop more refined and sophisticated techniques than PSA
testing to help identify more aggressive tumors early, reports James
Eastham, MD, of Memorial Sloan Kettering Cancer Center in New York
City.
One is the so-called 4Kscore test that
assesses the levels of four prostate-specific antigens to gauge a
man’s risk of having an aggressive cancer.
Another, called the prostate health
index, combines three PSA measurements to identify cancer and help
some men avoid a biopsy.
A third test, ExoDx Prostate
IntelliScore, examines biomarkers in urine to help predict a man’s
likelihood of having prostate cancer that will spread and become
deadly without treatment right away.
Researchers are also studying an
advanced form of MRI that can detect higher-risk prostate cancers.
In addition, other newly developed
tests and methods -- some based on molecular and genetic tests -- are
showing promise.
Samadi says these personalized,
next-wave tests are more precise tools that go beyond PSA testing to
help guide oncologists’ decisions on care, management, and
treatment of their patients.
Maurie Markman, MD, a medical
oncologist, believes this new breed of genetic tests and molecular
biomarkers will revolutionize cancer therapy.
“As time goes on, there will be
molecular markers that will be discovered that will help refine this
[to] actually predict with a much higher precision those patients who
will develop high-grade cancer or metastatic disease much better than
PSA or Gleason score,” says Markman, president of medicine and
science at the Cancer Treatment Centers of America. “That’s the
future.”
Improvements in Treatment
Samadi says some of these advances have
already improved prostate cancer detection and will continue to do
so.
But at the same time, vast improvements
have been in made in how doctors perform biopsies and treat cancer
with surgery, radiation, chemo, or hormone therapy (known as androgen
deprivation therapy), he says.
Major strides have been made in
surgical techniques (using less invasive laparoscopic and
robotic-assisted techniques), digital medicine (using MRI and other
scans), and more targeted radiation therapy. Meanwhile, clinical
trials are underway for new drugs designed to treat genetic factors
that drive cancers of all types.
Samadi says he’s also seen major
progress in treating prostate cancer as a result of changes in
American medicine since the 1990s.
“When I was in training in residency,
25-30 years ago, we would see people coming in with hard-rock
prostates, and we were doing a lot of surgery, chemo, hormonal
treatment, and radiation,” he notes. “But over the course of the
last 3 decades, a lot has changed, and [it] all happens to be good.”
For one thing, an elevated PSA no
longer triggers the “knee-jerk reaction” that a biopsy must be
done, and immediate treatment be sought if a tumor is uncovered.
And advances in MRI technology now
allow doctors to use imaging -- instead of surgical biopsies -- to
assess prostate tumors.
Twenty years ago, urologists would
randomly biopsy six or more areas of the prostate in a hit-or-miss
hunt for tumor cells that often required patients to have multiple
procedures.
“But today, we’re using more of a
targeted biopsy, we’re finding out where the lesion is, we go
straight into the lesion, and we’re able to find out exactly what
the cancer is,” Samadi says. “So it’s less invasive, less
headache, more targeted, and more intelligent.”
Radiation techniques have also improved
over the past 2 decades.
In the 1900s and early 2000s,
full-pelvis radiation was common, often causing serious
complications. But more precise radiation techniques -- involving
“CyberKnife” therapy and proton therapy -- can now be used to
deliver tiny, precisely aimed beams of radiation into tumor cells,
sparing healthy surrounding tissues and reducing complication risks.
Cancer specialists are also optimistic
about the promise of other therapeutics now in the pipeline.
Early research has found, for instance,
that cutting-edge prostate-specific membrane antigen (PSMA) scans can
identify high-risk cancers. These scans use radioactive tracers that
attach to PSMA, a substance often found in large amounts on prostate
cancer cells, and are now being used in some medical centers.
Another technique -- called
“radioligand therapy,” already approved overseas -- combines a
targeting compound that binds to cancer biomarkers to enable
precisely targeted delivery of radiation to the tumor, leaving
healthy surrounding tissue unharmed.
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In addition to these advances in
treatment options, Samadi says the approach to treating prostate
cancer -- particularly in older men -- has undergone a sea change.
Twenty years ago, men older than 70 were not considered good
candidates for surgery or other treatment, he says.
“But that concept doesn’t make
sense anymore today, and the reason is medicine has improved … and
we see a lot of people in their 80s and 90s,” he says.
For instance, Samadi says some of his
patients are 70 and older who are healthy, physically fit, and great
candidates for surgery because they are likely to live many more
years. On the other hand, he treats patients in their 50s who are
obese, diabetic, and/or have heart disease who aren’t likely to
benefit as much from prostate surgery.
“I look at my patients individually,”
he says. “If they are healthy and they are in good physical shape
and I think they would be an excellent candidate in the operating
room under my care, then I know this guy can be cancer-free with our
robotic surgeries and with good continence rate and good sexual
function, etc.”
The upshot: As more men are living
longer with prostate cancer as a result of improvements in
diagnostics, surgery, radiation, and other advances, treatment
decisions should not be based on age, PSA test results, or other
single-factor considerations alone.
“A one-size-fits-all approach is not
a good treatment plan,” Samadi says. “Individualized care is the
best way.”
Sources: © 2021 WebMD, LLC.
