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However, we are far from complacent: Our surgeons,
like our basic scientists, are always raising their standards of
excellence. Every day, we aim higher, because there is still so
much more that we want to do to help our patients. For example,
we are constantly seeking new ways to improve our surgical technique
and reduce side effects - through the use of nerve stimulators that
can help pinpoint these microscopic nerves more accurately; with
techniques that may enable the nerves to regenerate more quickly;
and with alternate medical therapies to help maximize the ability
of damaged nerves.
Finally, although the Brady Urological Institute
has achieved world renown for its prostate surgery, we know all
too well that this option is not ideal for every man. Thus, we continue
to evaluate and explore alternate forms of treatment, in the hope
that their efficacy may be improved and side effects reduced without
lessening the ability to cure the cancer.
The Partin tables
Currently, one of the most difficult truths we must face is that surgery
alone cannot cure cancer that has escaped the prostate. Who should
undergo surgery, and who should forego it? In recent years, this decision
has been far less agonizing, and much more objective, because of what
have come to be known as the Partin tables. Developed by urologists
Alan Partin and Patrick Walsh, these tables are everywhere: On Internet
websites, on laminated cards carried by doctors throughout the country,
even on home computer programs. Elegantly simple and meticulously
accurate, these tables have quietly revolutionized the way doctors
and patients are making decisions about treatment for prostate cancer.
Until these tables, there was no way to predict what urologists might
find when they opened up a patient during radical prostatectomy. Would
the disease be contained within the prostate, or would it have spread
- and thus, was the surgery unnecessary? We could guess, but we couldn't
be sure if microscopic, undetectable bits of cancer had already escaped
the prostate. These tables, correlating the three things that we could
know about a man's disease - PSA level, Gleason score, and clinical
stage - produced something that had been desperately needed. An accurate
means of estimating the exact extent of a man's prostate cancer before
surgery. Now these tables are even better, with the addition of 3,000
more patients.
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Better control of advanced disease
When Cancer Escapes the Prostate
The shadow of advanced prostate cancer, which today is not yet curable,
dims the luster of even our most promising findings and greatest accomplishments.
For until we can either prevent the disease, or detect it in time
in all men, we will continue to lose patients to this huge, overwhelming
enemy that we're still learning how to fight. For decades, scientists
have known that hormone therapy can hold advanced cancer at bay for
months or even years; it can ease many symptoms, often bringing a
dramatic improvement to quality of life. When a man starts hormone
therapy, the early results seem miraculous. The tumor shrinks, PSA
levels drop, and - most importantly - the man feels better. But then,
inevitably, the cancer makes a comeback, and PSA levels, which had
fallen so encouragingly before, begin to creep back up. Brady scientists
were the first to discover why this blessing of time and improved
health is so fleeting. Because prostate cancer is heterogenous - it's
made up of many different kinds of cells. Some of them respond brilliantly
to hormones; these cells aren't the problem. It's the other kind -
the cells that are hormone-resistant - that ultimately cause hormone
therapy to fail. Here, more than any other area, we are dedicated
to bringing new approaches as quickly as possible from the bench
to the bedside. Although most of these new strategies are not yet
ready for patients, their promise gives us more hope than we have
ever before been able to offer. Briefly, these include:
Angiogenesis inhibitors
The idea here is a big-roadblock. Picture the steam engines of a
century ago, inching their way across the American west, a few lengths
of track at a time. Before prostate cancers can spread they, too,
lay down a track of new blood vessels. (This guarantees a ready-made
supply of nutrients - nourishing meals for the road - which, it
seems, these cancers absolutely cannot do without.) Destroy this
infrastructure, cut off the supply line, block these new blood vessels
and the cancer cells starve. This building of new blood vessels
is called angiogenesis; it's a normal process your body uses to
heal wounds. Drugs to block it, called angiogenesis inhibitors,
already exist. Side effects are minimal; these drugs target the
blood vessels only in areas of cancer. John Isaacs has been working
with an angiogenesis inhibitor called Linomide, which does a beautiful
job of stalling tumor growth. Although no angiogenesis inhibitor
can cure prostate cancer, there is great promise that Linomide or
a similar drug can keep it from growing, or put its growth in slow-motion,
for years or even decades - so a man may still have prostate cancer
cells in his body, but they would not kill him.
Other approaches
But an angiogenesis inhibitor won't do enough to fight more advanced
disease. Starting the drug once cancer has become entrenched - when
it starts producing such symptoms as bone pain - would offer too
little help, too late. Clearly, a more drastic tactic is needed
for these men, who need effective long-term treatment most of all,
and Isaacs has some ideas for them, as well. Most promising is a
drug called thapsigargin - a compound derived from a Mediterranean
plant that resembles parsley - that works by burrowing its way into
a cell and targeting a protein that acts as a calcium pump. This
pump keeps calcium from rising above a certain level inside a cell.
Why is too much calcium bad for a cell? Because it acts as a chemical
key, which jumpstarts a genetic process called programmed cell death.
A glut of calcium inside a cell short-circuits it, activating a
"suicide pathway" - it causes the cell to kill itself.
Isaacs is working to genetically tailor this drug so that it only
targets cells that make PSA. Laboratory tests indicate that this
compound, if successful, will be able to kill prostate cancer cells
in a matter of days.
A Vaccine to Prevent Prostate Cancer
Taking yet another tack against advanced disease, Jonathan Simons
and Fray Marshall are working to program the body's DNA like a computer
chip, sending it on a selective search-and-destroy mission targeted
only at prostate cancer cells. Their goal is gene therapy the body's
own tools, DNA molecules, to treat cancer that can't be cured by
surgery or radiation - and they're coming at it from two angles:
Genetically engineered "vaccines" made from cancer cells,
and doctored viruses that act as Trojan horses, slipping into the
body, attaching themselves to prostate cancer cells and exterminating
them before they even suspect anything's amiss.
Years ago, the Brady Urological Institute developed
an unprecedented multidisciplinary collaboration with oncologists,
who are applying their own expertise to the frustrating challenge
of treating advanced prostate cancer. Oncologist Mario Eisenberger
and colleagues are working to develop, test and refine several experimental
drugs, each of which works in a slightly different way, to fight
hormone-resistant cancer.
And finally, urologist Joel Nelson has turned his
attention to making life better for patients suffering from the
bone pain of prostate cancer - a particularly horrible, debilitating
agony that defies just about every painkiller except morphine. In
the past, this terrible pain has always been accepted as one of
the most grim aspects of prostate cancer. But Nelson's work suggests
another culprit: One of the body's own chemicals, called endothelin
(made by the prostate and other organs) -- which bears an amazing
structural resemblance to snake venom and apamin, the toxin that
causes the pain in bee stings. He believes that at least some of
this extreme pain happens because the cancerous cells are secreting
endothelin. If this compound could be blocked, the pain - and perhaps
other bone changes, as well - might be prevented. The potential
to improve quality of life for these patients is staggering.
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