Issue 13April 2008
What's inside this issue
- Treatment of high risk prostate cancer
- Early detection and best treatments for men with prostate cancer
- Diet and Prostate Cancer
- Measuring Treatment Response
- GPS for the Body
- Gamma Knife Technology
- Prostate Cancer Team
Consult with an SCCA Specialist through the Free MEDCON Service:
From F. Marc Stewart, MD, Medical Director, SCCA; University of Washington Professor of Medicine; Member, Fred Hutchinson Cancer Research Center Prostate cancer is a large concern to men in our society, especially as the medical community continues to see more obesity in the population.
This quarter, SCCA’s The Leading Edge Newsletter is focused on prostate cancer and the current research for its treatment and early detection, as well as factors that may lead to changing the actual biology of prostate cancer. SCCA has initiated a program specifically designed to identify better ways of treating men with prostate cancer defined as “high risk” despite local therapy, and, in findings currently at press in the journal Cancer Research, indicating that prostate cancers evolve in response to androgen suppression in the blood, and begin to synthesize androgens from very early precursors such as cholesterol.
I trust the information in this issue will interest and educate you in some way. Please let us know if you have any comments about the content or would like us to feature a specific topic in future issues. Standard fare in every issue, you’ll find phone numbers for referring your patients or consulting with an SCCA physician.
Seattle Cancer Care Alliance (SCCA) has initiated a program specifically designed to identify better ways of treating men with prostate cancer defined as “high risk” despite local therapy.
In contrast to low- grade, low-volume cancer, 20 percent of men present with cancer that is high-grade or high-volume, or makes high levels of PSA. These men are at very high risk for progression of their cancer despite surgery or radiation. The reasons why progression happens despite the best possible local therapy to the prostate are complex, but most physicians believe that this reflects the propensity for high grade prostate cancer to spread early in its genesis, leading to systemic micrometastasis. At present the only available treatment used to treat these micrometastases is androgen suppression, which is effective transiently for most patients.
Physicians at SCCA are taking advantage of a discovery about why androgen suppression may not work in many men with advanced cancer. The team, led by Elahe Mostaghel, MD; Bruce Montgomery, MD; and Pete Nelson, MD have found that androgensynthesizing proteins are present within prostate cancer cells, suggesting that cancer cells develop the capacity to produce their own testosterone, completely independent of endocrine organs. The findings, currently in press in the journal Cancer Research, indicate that prostate cancers evolve in response to androgen suppression in the blood, and begin to synthesize androgens from very early precursors such as cholesterol. The team conducted tests on metastatic tumors removed from patients who had received androgen-blocking therapies during the course of treatment to suppress tumor growth. They were able to detect the key proteins, or enzymes, in the tumors needed for a cell to produce its own testosterone from cholesterol present in the cell.
“We were amazed to find that metastatic cancer in men treated with hormone suppression had levels of testosterone up to 5 times higher than untreated prostate cancers,” said Mostaghel. “The presence of the cell machinery necessary to make its own growth factor makes this an example of “intracrine” growth hormone production and gives us a wonderful way to make our most effective systemic therapy much more effective.”
Dr. Pete Nelson, senior author of the study, noted that the results offer directions for future research in this area. “The next phase will be to determine the source of androgen precursors. These are likely to be derived from adrenal androgens, or possibly from cholesterol. A key experiment will be to follow these precursor molecules in the cancer cells to see if they are converted to testosterone,” said Nelson, “hence proving these tumor cells are actually capable of such a conversion.” He also suggests that these findings are similar to those discoveries made in breast cancer, which led to the development of aromatase inhibitors, which are more effective treatments for that hormone dependent disease.
The SCCA team of urologists, radiation oncologists, and medical oncologists has developed a program designed to leverage these findings by combining new drugs to better treat micrometastatic prostate cancer. All of these studies are designed to better treat men undergoing surgery or radiation to cure their cancer. “Any way that we can better kill cancer that might have spread is a better way to cure men with this disease,” says Montgomery. “We have to get away from our old ways of thinking about prostate cancer only as a problem in the prostate, and think about how to treat the rest of the body as well. We think that the leading-edge research offered at SCCA gives us the insights into how to really improve cure of this disease. We are testing antibodies, tyrosine kinase inhibitors, and inhibitors of androgen synthesis for men with high risk cancer, to try to get the answer to this problem as quickly as possible.”
For more information, contact Elahe Mostaghel, MD; Bruce Montgomery, MD; and Pete Nelson, MD at (206) 288-SCCA (7222).
SCCA is leading the effort to develop ways of deciding which men need aggressive treatment for prostate cancer and which can be spared surgery or radiation if it isn’t needed.
Investigators Daniel Lin, MD and Peter Nelson, MD are leading a team of researchers in a study called Canary PASS (Prostate Active Surveillance Study), supported by the Canary Foundation (www.canaryfoundation.org) to identify markers which will allow physicians and their patients to choose their best options for therapy. The team is investigating blood and tissue markers that can identify who has prostate cancer, which prostate cancers can be safely watched, and which cancers may benefit from aggressive local or systemic therapy. The Canary Foundation intends to fund the study for at least three years.
The SCCA team includes Larry True, MD; Ruth Etzioni, MD; Janet Stanford, MD; Robert Vessella, MD; and Ziding Feng, MD as well as investigators from University of British Columbia, Stanford; University of California, San Francisco; and University of Texas, San Antonio. Contact study coordinator Lisa Newcomb at (206) 667-1946, firstname.lastname@example.org.
Vitamin-E/ Selenium Supplements
SCCA researchers are investigating how diet and lifestyle changes can change prostate cancer biology. Alan Kristal, PhD and Cathy Tangen, PhD, are key investigators in a 35,000-man, multi-center trial investigating whether vitamin E or selenium supplements can prevent prostate cancer, with results expected in 2012.
Kristal, Tangen, and Marian Neuhouser, PhD are also collaborating on an international effort to understand the biology of prostate cancer risk using blood and prostate tissue collected during the Prostate Cancer Prevention Trial. These studies are examining the roles of steroid hormone metabolism; diet and obesity; inflammation; insulin and insulin-like growth factors; DNA damage; and genetic characteristics based on almost 2,000 prostate cancer cases and 2,000 controls.
One early finding demonstrated a complex association of obesity with cancer risk: obesity decreased the risk of low-grade but increased the risk of high-grade cancer. In a further collaboration, Janet Stanford, PhD found that among men diagnosed with cancer, obesity more than doubled the risk of dying of prostate cancer. This risk was elevated regardless of treatment (radical prostatectomy, hormone therapy, or radiation), cancer grade, or cancer stage.
Broccoli – cancer prevention agent
In another direction of research, several years ago Kristal and Stanford reported that consumption of broccoli was associated with a substantial reduction in prostate cancer risk. Our group has been interested in understanding this association, with the hope of developing a randomized clinical trial to test compounds in broccoli as a cancer prevention agent. Toward that goal, Daniel Lin, MD; Alan Kristal, PhD; and Beatrice Knudsen, MD are collaborating to evaluate whether sulforphane, a compound found in broccoli that has extraordinary activity in both upregulating expression of anti-oxidant enzymes and decreasing proliferation of cancer in in vitro and animal models, has similar effects in the human prostate. Over the next few years, these in-progress studies should help us better understand how to prevent prostate cancer and increase the chance of survival among cancer patients.
Patients with prostate cancer need more than just a diagnosis and a treatment. They need personalized care to determine exactly how well they are responding to a specific therapy.
SCCA physicians and health-care providers recognize this. The prostate cancer research group has teamed with the nuclear medicine group to address this issue. The team, led by Evan Yu, MD (oncology); David Mankoff, MD (nuclear medicine); Bruce Montgomery, MD (oncology); and Janet Eary, MD (nuclear medicine), have joined forces to evaluate novel imaging techniques as prostate cancer biomarkers.
“Our first step was to consider the biology of a prostate tumor and capture this with a technology that could not only detect but also measure the activity of the tumor,” says Mankoff. “This led us to look at lipid metabolism and 11C-acetate as a probe for positron emission tomography (PET) imaging.”
Multiple studies have preliminarily shown that localized and metastatic prostate cancer not only uptake his probe, but that the amount that is taken into the tumor sites vary in response treatment.
“This is very exciting because standard methods of measuring prostate cancer response to treatment have many problems and lack in overall accuracy. Our hope is that someday, we can not only track what is going on in the tumor after treatment, but we will be able to predict and select therapies based on what we see with our images. That will move us closer to personalized cancer medicine and even help us develop effective new drugs!” Mankoff says.
Mankoff is enthusiastic about this approach because he has performed such work before with breast cancer.
“I’m excited about the work with Dr. Yu and the prostate group,” he says. “It builds upon our prior experience, addresses important clinical problems for a new group of patients, and forms a collaboration with one of nation’s leading prostate cancer groups.”
These results have led to an expansion of the collaboration between the prostate cancer and radiology research groups. There are plans to further develop PET imaging with novel probes that look at other aspects of prostate cancer biology. Additionally, magnetic resonance imaging and spectroscopy (MRI/MRS) has similar capabilities to image and detect specific proteins that become altered during treatment. Plans are underway to incorporate these exciting new technologies.
Calypso Medical manufactures the Calypso® System, which they now call GPS for the Body – a leading-edge technology that provides clinicians with an innovative solution for target localization and monitoring of the prostate continuously and in real time during radiation therapy delivery. The common methods used for target localization don’t have this capability. Seattle Cancer Care Alliance provides this additional support with every external beam radiation treatment.
GPS for the Body uses miniature Beacon® electromagnetic transponders that work with the Calypso System to expertly assist radiation oncologists to accurately align the prostate before each treatment and precisely monitor the position of the prostate at all times during treatment delivery. Accuracy of treatment is enhanced and additional non-ionizing radiation doses are not needed. The Calypso System displays and records prostate motion—continuously in realtime— through an intuitive graphical user interface. Visual and audio cues communicate prostate motion when the organ moves outside of the treatment thresholds to ensure the most accurate treatment possible.
“We would like to use it for all men who are having primary external beam treatment for their intact prostate,” says Dr. Ken Russell, SCCA urologist. “Presently, we do not use it in men who have had their prostate removed and who receive post-operative radiation for residual cancer. There are also some men with intact prostates in whom we would like to use it but in whom Calypso can not be used: men with metal hip prostheses, indwelling metal cardiac pacemakers or defibrillators, and men who are too physically large. So we offer it to all men who meet the eligibility criteria as outlined above.”
Gamma Knife technology first became available in 1968, revolutionizing the treatment of human brain diseases.
The University of Washington Gamma Knife Center, which is located at Harborview Medical Center in Seattle, is one of the first sites in the country to offer the latest in Gamma Knife technology – the Model 4C.
Minimally invasive, radiosurgery treats patients with brain abnormalities or lesions that are too close to delicate structures and blood vessels. It requires little or no anesthesia, offers a fast recovery time, and is safer and less costly than surgery or full-brain radiation.
Patients with arteriovenous malformations and functional brain disorders such as Parkinson’s disease have significantly improved options for treatment with the Gamma Knife technology. Of the nearly 100,000 Gamma Knife procedures that have been performed since 1968, almost one-third of these patients sought relief from blood vessel problems (i.e. AVMs).
Nearly two-thirds were treated for brain tumors, including the more common acoustic neuromas, meningiomas, pituitary tumors, metastatic cancer, glial tumors and rarer types of tumors. A small percentage sought treatment to relieve functional disorders like unmanageable pain, trigeminal neuralgia, Parkinson’s disease and epilepsy.
Typically, patients are seen in consultation and initially by a neurosurgeon or a radiotherapist followed by a radiosurgery panel evaluation.
SCCA neuro-oncology patients have access to this leading technology.
Physicians can refer patients to the Gamma Knife Center at Harborview by calling (888) GAMMA-68 (888-426-6268) or by calling (206) 288-SCCA (7222).
How do I refer a patient? Call our Intake Office at (206) 288-1024.
General oncology patient case discussions will be transferred to the appropriate Patient Care Coordinator.
Marrow or stem cell transplant patient referral cases will be transferred to the Clinical Coordinator. We will review the case with you to determine if it would be beneficial for the patient to come to SCCA for treatment.
What happens after referral? SCCA is committed to ongoing communications with referring physicians to maintain seamless patient care. UW Medicine offers a secure electronic connection through U-Link to give you instant access to your patient’s information and updated records while at SCCA. Contact the Physician Liaison Program at (206) 598-4972 to sign up. Current users may access U-Link at: https:// mindscape.mcis.washington.edu/
Medical Oncology /Endocrinology
- Bruce Montgomery, MD, UW Division of Oncology, Associate Professor
- Pete Nelson, MD, UW Division of Oncology, Associate Professor
- Elahe Mostaghel, MD, Fred Hutchinson Cancer Research Center, Associate in Clinical Research
- Celestia Higano, MD, UW Division of Oncology, Associate Professor
- Evan Yu, MD, UW Division of Oncology, Assistant Professor
- James Dean, MD, UW Division of Oncology, Action Instructor
- Stephen Plymate, MD, UW Division of Gerontology and Geriatric Medicine, Professor
- Dan Lin, MD, UW Department of Urology, Assistant Professor
- Bill Ellis, MD, UW Department of Urology, Professor
- Paul Lange, MD, UW Department of Urology, Professor, Chairman
- Tom Takayama, MD, UW Department of Urology, Associate Professor
- Jonathan Wright, MD, UW Department of Urology, Resident
- Ken Russell, MD, UW Department of Radiation Oncology, Professor
- Jay Liao, MD, UW Department of Radiation Oncology, Assistant Professor
PDF of this issue of The Leading Edge.
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The SCCA Adult Bone Marrow Transplant News is a publication presenting the latest information on bone marrow transplant research at SCCA, providing up-to-date information for all health care professionals caring for transplant patients.
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Each issue of Clinical Trials Monthly highlights several of the more than 200 clinical trials that are currently recruiting patients at SCCA.
Each quarterly Leading Edge newsletter will highlight a new topic to give you the latest news on leading-edge therapies that SCCA physicians are offering.