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Physicians Update
Screening Markers, Imaging Allies in Fight Against Prostate Cancer
The introduction of new molecular markers to screen for prostate cancer is helping to further advance diagnosis and treatment of a disease that is known for its complexity.
Among the screening markers increasingly used is PCA3, an RNA molecule that is produced by prostate cancers but not normal glands. Studies have shown that when PCA3 is found in the urine after a prostate exam, it almost always indicates the presence of cancer. PCA3 is positive in as many as 70-80 percent of men who have prostate cancer. “PCA3 has become a useful adjunct to routine PSA screening,” says Professor of Urology Robert Reiter, M.D., director of the UCLA Prostate Cancer Program, which is the only National Cancer Institute-designated Specialized Program of Research Excellence for prostate cancer in California. “We have begun to use it as a test for men about whom we have a high suspicion of prostate cancer but whose biopsies are negative.”
Molecular markers are also helping physicians make better decisions about treatment by providing important new prognostic information. UCLA researchers have, for example, found that loss of a protein called p27 portends a poor prognosis in men undergoing surgery. Over the past few years, investigators have discovered that certain fusions of the TMPRSS2 gene with one of a family of ETS genes may also be associated with a poor prognosis.
These fusions can also be used to discriminate cancer from surrounding normal tissue, and to determine whether some precancerous lesions are likely to be associated with an invasive tumor. Armed with that knowledge, physicians in the UCLA program are beginning to test patients with prostate cancer for the presence of such fusions to determine their clinical utility. These fusions may turn out to assist in clinical decisions, similar to p27 and other molecular markers.
Imaging is also becoming a greater ally. “One of the biggest barriers to effective treatment of prostate cancer is that we haven’t had good ways to identify the cancer with conventional imaging, and so we have had to make important decisions without solid information,” Dr. Reiter explains.
In recent years, magnetic resonance spectroscopy has been used for all patients scheduled to undergo robotic prostatectomy, to pinpoint the location of the tumors within the prostate gland as well as to gain a better sense of whether they have spread beyond the prostate capsule. “We now have a roadmap going in that enables us to individualize each patient’s surgery,” Dr. Reiter says. “This has improved our ability to preserve sexual nerves in some patients, and has helped us to more completely remove the cancer in others.”
A more recent development in prostate cancer imaging at UCLA involves the acquisition of experimental technology that can merge MRI and ultrasound images to obtain a three-dimensional picture of where the cancer is located at the time of biopsy. If effective, this could improve the sensitivity of office biopsies and eventually lead to the ability to perform the prostate version of a breast lumpectomy — focal treatment of the prostate lesion rather than removal or radiation of the entire prostate.
For localized prostate cancer, robotically assisted surgery continues to play an increasingly important role. UCLA has obtained a second robotic surgical system, the da Vinci S, which has enabled the Prostate Cancer Program to expand the number and scope of its robotic procedures. The ability to achieve results that are comparable to open surgery when it comes to eliminating cancer and preserving sexual potency and urinary continence makes the robotic approach attractive to many patients with early stage prostate cancer, Dr. Reiter says. Virtually all patients leave the hospital the morning after surgery and are able to return to work within a month.
In radiation therapy, the difference between what is available today and what was used a decade ago is “like night and day,” says Michael Steinberg, M.D., chair of radiation oncology at UCLA. The armamentarium for radiation therapists now includes image-guided radiation therapy, intensitymodulated radiation therapy, and permanent-seed and high-dose-rate interstitial implants. These new forms of radiation therapy can treat prostate cancer primarily as well as an adjunct for certain patients after radical prostatectomy.
“We are now able to precisely paint the radiation dose right where we want it,” Dr. Steinberg says. “We can bend it around critical structures like the bladder and rectum so that we can kill the cancer with minimal side effects.”
Watch and Wait
While newer technologies are increasingly enabling physicians to aggressively attack prostate cancer, there has been a recent push toward “active surveillance” — closely watching rather than treating certain patients. At UCLA, this approach is aided by many of the latest advances that are incorporated into the Prostate Cancer Program, including the use of molecular markers and imaging to make better decisions about which patients might not need immediate treatment but can instead be followed. More patients are being encouraged to be followed rather than submit to the potential side effects associated with all current local therapies.
Clinical Trial Programs
UCLA has a dedicated program of clinical trials for prostate cancer at all stages of the disease. One of the most closely watched trials, currently in phase III, involves the drug abiraterone, which has shown dramatic results in patients
with advanced prostate cancer that no longer responds to hormonedeprivation therapy. The drug takes advantage of basic research on the role of the testosterone pathway in end-stage prostate cancer. Other studies are underway to test the ability of so-called endothelin-receptor-antagonist drugs to prevent bone metastasis in patients with recurrent cancer, and the ability of angiogenesis inhibitors to improve the efficacy of chemotherapy for advanced
prostate cancer, explains Matthew Rettig, M.D., who heads clinical trials for prostate cancer. Trials are also offered for patients at the earliest stages of the disease, including patients who, after radical prostatectomy, are considered to be at high risk for recurrence. Such patients are offered a short course of hormone therapy in conjunction with a synergistic drug in an effort to induce a medically complete remission that can be detected at the time of surgery. For patients whose only evidence of disease recurrence after surgery is an elevated PSA, pomegranate juice is being tested for its ability to prevent metastasis.
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