Mohamad E. Allaf, M.D.
Trinity J. Bivalacqua, M.D, Ph.D
Arthur L. Burnett, II, M. D.
H. Ballentine Carter, M.D.
Misop Han, M.D.
Jacek L. Mostwin, M.D., D.Phil,(Oxon.)
Alan Partin, M.D., Ph.D
Christian Pavlovich, M.D.
Edward M. Schaeffer, M.D., Ph.D.
Patrick C. Walsh, M.D.
It is not enough to diagnose prostate cancer early, if the cure is perceived as worse than the disease itself. This was the case 20 years ago, when the radical prostatectomy (developed by Hugh Hampton Young at Johns Hopkins nearly a century ago) was infamous among surgeons and patients for its extreme, often life-threatening bleeding and devastating side effects: One-quarter of the men who survived the operation were left with severe incontinence, and all of them were impotent. The very harshness of the procedure was the catalyst- for change, inspiring the anatomical discoveries that have drastically reduced these side effects.
Today, radical prostatectomy cures the vast majority of men with cancer confined to the prostate preserving potency. - by not removing one or both of the nerve bundles adjacent to the prostate (surgeons didn't even realize these bundles existed two decades ago), which are responsible for erection - does not compromise cancer cure; a recent study found that the odds of cure are just as high. Today, serious bleeding is very rare, preserving potency is common, and few suffer from serious incontinence. In fact, the radical prostatectomy series at the Brady Urological Institute is considered to be the gold standard for cancer cure, to which all other forms of treatment are compared.
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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:
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.
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.