In a bid to improve treatment for men with
high-risk prostate cancer, some researchers want to take a page from the
playbook for breast cancer.
Medical
scientists are working to develop strategies for treating prostate
tumors that are tailored to individual patients, as is currently done
for many women with breast cancer. Fresh advances in the understanding
of prostate cancer suggest that some men with a high-risk form of the
disease might benefit from more aggressive treatment.
67
The average age of prostate cancer diagnosis. The chance of having it rises rapidly after age 50.1 in 36
Men will die of prostate cancer, the second leading cause of cancer death in American men, behind lung cancer.Inside a Prostate-Cancer Cell
Other men may benefit from less
treatment. For instance, radiation plus hormone therapy, also called
androgen-deprivation therapy, is a common strategy to kill prostate
tumors. But a recent study from researchers at Memorial Sloan-Kettering
Cancer Center suggests that analyzing a tumor's DNA may identify
patients who would do just as well with radiation alone. If borne out in
further research, some men may be able to skip hormone therapy,
avoiding side effects that include loss of libido and heart disease.
The
developments come amid changes in the way many types of cancer are
identified and treated. The changes are being driven in part by the use
of genomic information that defines tumors by their underlying biology
and provides clues about drivers of the disease not available by
conventional exams.
Researchers say, for
instance, that several new genomic prostate-cancer tests can help
separate high-risk tumors from those at low or intermediate risk,
offering information to doctors and patients to guide treatment choices.
About
240,000 men in the U.S. are diagnosed with prostate cancer each year.
Most cases are low-risk forms of the disease that will have little
effect on their lives or longevity. In these cases, a big concern is
that overtreating the cancer puts these men at unnecessary risk for
impotence, incontinence and other complications.
About
20% of diagnosed men are considered at high risk for having their
cancers spread beyond the prostate gland based on a measure called the
Gleason score and other factors. For some men with an aggressive form of
the disease, the 10-year-survival rate is well below 50%. "We may not
be treating them aggressively enough," says
William Polkinghorn,
a radiation oncologist at Memorial Sloan-Kettering, in New York.
Some
95% of men who die of the disease are initially diagnosed with cancer
that is confined to the prostate region, says Philip Kantoff, director
of the Lank Center for genitourinary oncology at the Harvard-affiliated
Dana-Farber Cancer Institute, in Boston. Finding ways to "cure" such
patients is "mission central," he says. Once cancer spreads beyond the
prostate—typically to the bone—it is considered incurable.
The
current standard of care for high-risk prostate cancer is either
surgery to remove the cancerous gland or radiation plus hormone therapy
to kill the tumor. Some men get radiation after surgery, but generally
the two approaches aren't given together.
By
comparison, women with high-risk breast cancer, which like prostate
cancer is also typically fueled by sex hormones, typically get a
combination of surgery, radiation and drugs. Medicines are tailored to
patients based on whether the hormones estrogen and progesterone or a
gene called HER2 is fueling the tumor.
Aggressive
treatment of these women has resulted in improved survival and relapse
rates, says
Charles Sawyers,
head of the human oncology and pathogenesis program at Memorial
Sloan-Kettering. Whether a similar approach would improve survival for
high-risk prostate cancer isn't certain but it is "a conversation that
needs to be had in a more vigorous way," he says.
There
is some evidence it could work. Research from clinical trials, for
instance, suggests that giving radiation soon after surgery increases
the time a patient lives without the disease coming back, says Adam
Dicker, head of radiation oncology at Jefferson Medical College of
Jefferson University, in Philadelphia.
But
there have been few studies looking at the effect of combining
treatments. It can take 10 to 15 years to complete a trial testing a
multipronged strategy versus a single-treatment approach.
Genetic
tests have recently become available that examine tumors for molecular
signatures that predict whether a tumor is high- or low-risk and can
help doctors make treatment decisions.
A
test marketed by San Diego company GenomeDx Biosciences Inc. yields a
molecular profile that can indicate, for instance, whether a man who
undergoes prostate surgery to remove the tumor would also benefit from
radiation treatment, says
Doug Golginow,
the company's chief executive.
It
"doesn't tell you if a specific chemotherapy" will work against the
tumor, but "it sorts out a lot of confusion by telling you whether you
have the kind of disease that's going to kill you or not kill you," he
says.
Genomic Health Inc.,
GHDX -2.93%
in Redwood City, Calif., and
Myriad Genetics Inc.,
MYGN +0.39%
of Salt Lake City, sell tests that, for instance, can help
distinguish between high- and low-risk prostate cancers, possibly
enabling men to delay or forgo aggressive treatment.
Dr.
Polkinghorn's research at Sloan-Kettering yielded another genetic
signature that could tell men when they need less therapy. He led a
recent study that showed androgen's role in prostate cancer goes beyond
providing fuel for the tumor's growth; the male sex hormone also
activates androgen receptors that turn on genes which repair damaged
DNA. The finding is important because radiation kills tumor cells by
breaking DNA. It also explains a two-decade-old mystery over why
combining radiation with anti-androgen drugs is significantly more
effective against high-risk cancer than radiation alone.
Depriving
the tumor of androgen "takes the sunscreen off the prostate cancer cell
and makes it more sensitive to radiation," Dr. Polkinghorn says. The
report was published in November in the journal Cancer Discovery.
The
analysis revealed that levels of androgen-receptor activity vary widely
between patients. This suggests that patients with high androgen
activity may benefit from hormone therapy while those with low activity
levels may gain little from it and could forgo the treatment
The
researchers plan to validate the result by testing it on a database of
prostate-tumor specimens gathered from a variety of clinical trials
where the outcomes of the patients are known.
Dr.
Polkinghorn now runs a clinic for high-risk prostate-cancer patients.
He and his colleagues are developing a protocol to test how well such
patients respond to more aggressive therapy.
Howard
Bellin, a 77-year-old recently retired plastic surgeon who had surgery
to remove his cancerous prostate in October, is being treated with the
approach. The conventional strategy, Dr. Bellin says, is for doctors to
wait after surgery to see if the tumor comes back and then "go after it
with bigger guns" or hormone therapy. He says he is being treated now
with two hormone drugs and radiation, hoping that a cure lies in
"treating it with your big guns right away."
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