Agenda Talk Descriptions

The 2007 National Conference on Prostate Cancer
State of the Art Treatments:
Making a Positive Impact on Quality of Life

Marriott Hotel Los Angeles Airport, California

September 7, 2007

Friday Afternoon: Getting a Perspective

1:15 Color Doppler Biopsy Demonstration
Duke K. Bahn, M.D. and Fred Lee, M.D.

Color-Doppler Ultrasound improves the diagnosis and staging of prostate cancer. This state of the art imaging visualizes the prostate gland much more clearly than standard ultrasound technology. Additionally, when abnormalities are detected, a needle biopsy can be directed specifically to that area, resulting in more precise findings than the usual approach which uses a random biopsy. Therefore, using this technology means that fewer biopsy cores are required to make an accurate assessment.

Color-Doppler ultrasound can also provide important staging information in men who have already been diagnosed with prostate cancer from a previous random biopsy. Current methods for determining the presence of extra-capsular disease rely almost exclusively on statistical estimations. Unfortunately many of these estimations have only a 50% probability of being correct. Color-Doppler ultrasound imaging with directed peri-prostatic biopsies can make an unequivocal pathological diagnosis of extra-capsular disease. This allows the patients and doctors to have much more accurate information for making an optimal treatment plan.

3:00 Prostate Pathology
David G. Bostwick, M.D., M.B.A.

The Gleason score has long been the standard for evaluating prostate cancer biology. The revolution of genomic and proteomic testing has spawned a variety of new diagnostic and therapeutic biomarkers. The most promising available new marker for early detection of prostate cancer is the uPM-3 test, a simple urine-based assay that is much more accurate than serum PSA. The use of alpha-methyl-coA-acetyl-racemase has become standard practice in tissue diagnosis. These and other markers will be discussed as models for improving prostate cancer patient management.

3:45 Staging, Risk Management, and Active Surveillance
Mark C. Scholz, M.D.

Once men get past the initial shock of a prostate cancer diagnosis, they are faced with a confusing situation. Different specialists may advocate surgery, radiation or even foregoing treatment altogether. This controversy is only partially explained by the differing medical viewpoints of urologists, radiation therapists and oncologists. It turns out that prostate cancer itself occurs in many types and stages. Fortunately these varied forms of the disease can be grouped into four major categories. Naturally, appropriate treatment varies by category. How an individual is assigned to one of these four categories using readily available indicators such as PSA, PSA velocity, PSA density, PSA nadir, Gleason score, biopsy information, physical examination, and scan findings is addressed in this talk.

These days most types of newly-diagnosed prostate cancer are not very life-threatening. As a result, avoiding treatment-related side-effects like impotence, incontinence or rectal burns is exceptionally important. Among the available treatment options, there is only one that has no side-effects at all—active surveillance. As crazy as it sounds, forgoing immediate treatment is rapidly gaining acceptance as a bona fide treatment option. However, all the available treatment options—surgery, IMRT, seeds, cryotherapy, testosterone blockade, and active surveillance—have their advantages and disadvantages. The ultimate goal of this talk is to provide newly-diagnosed men with a workable framework for selecting optimal treatment while at the same time minimizing the risk of unnecessary toxic side effects.

4:30 Navigating Medicare
Arthur N. Lurvey, M.D.

Nearly all the diagnostic and therapeutic services related to benign prostate disease and prostate cancer detection and treatment are available to patients under the Medicare program. Dr. Lurvey, a Medicare Contractor Medical Director, will discuss the various options and how to make sure patients and their families can access all the services available; including tests, treatments, hospital facilities, medications, therapies, home health, and clinical trials. He will also review the Internet access available to Medicare subscribers.

September 8, 2007

Saturday Morning: Prostate Cancer Essentials

8:30 Minimizing Prostate Cancer through Diet
Colin Campbell, Ph.D.

Over the past 50 years, my research at Cornell University has been aimed at the effect of diet and nutrition on cancer and chronic disease. My research group has been primarily focused on the development of fundamental biological principles that could help to explain relationship between cancer and diet. Our research, in conjunction with the extensive work of others, suggests that a diet low in animal protein prevents the development of cancer. We have also found that this type of diet suspends or even reverses cancer growth in its late stages. A low animal protein diet also helps to ward off a plethora of chronic illnesses.

9:15 Magnetic Resonance Imaging
Combidex, Spectroscopy, & Bone marrow imaging
John Kurhanewicz, Ph.D.

Magnetic Resonance Spectroscopic Imaging (MRSI) and traditional MRI in combination provide both metabolic and anatomic information about prostate cancer. This technology can significantly improve the clinical assessment of prostate cancer by:

1. Locating and determining the extent of the cancer within the prostate
2. Determining the presence or absence of extra-capsular spread
3. Estimating cancer aggressiveness.

Previously this technology was only available on a research basis. Now however, multiple commercial MRI/MRSI packages are currently available. Two ongoing multi-center trials evaluating the accuracy of this technology are almost complete.

Additional new research is continuing to improve the accuracy of MRI/MRSI. One approach is the use of stronger magnetic field scanners (3 Tesla versus 1.5 Tesla) which increase the ability to detect even smaller cancers by improving spatial resolution. Several research centers are also developing other methods to further improve the accuracy of prostate MRI/MRSI. New methodology can now image the tissue microstructure in cancer by measuring how quickly water diffuses across tissue planes. Another new technique takes a closer look at tissue vascularity with intravenously administered contrast. Both of these new enhancements are focused on improving the accuracy for evaluating the extent of prostate cancer inside the prostate gland. However, there is also another method in development for detecting early spread of prostate cancer to the lymph nodes in the lower abdomen. This new approach uses another type of intravenous “contrast dye” that consists of magnetic nanoparticles.

Ultimately, as these new technologies are refined and are commercialized, it appears that the most accurate detection and characterization of prostate cancer will occur by combining all of these techniques into a single imaging exam.

In this presentation, the current clinical status of magnetic resonance imaging of prostate cancer will be presented with an emphasis on both the value and limitations of the imaging data and how to combine the imaging information with other clinical information to provide the best assessment of prostate cancer.

10:30 Impact of Supplements
Lycopene, Selenium, Vitamin E & D, Zyflamend,
Curcumin, MCP, Pomegranate
Charles “Snuffy” Myers, M.D.

In the laboratory, there is now extensive information linking oxidative damage and inflammation to the development and progression of prostate cancer. Furthermore, there are multiple clinical trials that have reported that antioxidants and anti-inflammatory agents slow the progress of prostate cancer. However, in no case do we have a definitive randomized controlled trial that tests any of these agents in the management of prostate cancer. Instead, what we do have are large randomized controlled trials where a benefit of antioxidants emerged as a side effect of using these agents to manage other diseases. Until appropriate randomized controlled trials are done, these agents will remain unproven as treatment for prostate cancer. Should you use these while we await proof? We will review the risk vs. benefit of using these agents based on the presently available evidence.

Finally, there are a number of supplements offered via the internet that are problematic. Some lack any evidence of effectiveness in humans. Others lack critical safety data. Some supplements are noted for breaking down rapidly and available products are offered with no evidence that they remain active. Finally, our experience with vitamin D suggests that the supplement industry, with few exceptions, cannot be depended on to deliver a quality product. This creates a problem because even where a supplement has proved to be effective in clinical trial, there may be no way for you to be sure that the product you buy will be effective.

11:15 Low-Impact Pharmaceuticals
Avodart, Calcitriol, Avandia, Atacand, Celebrex
Stephen B. Strum, M.D.

The Prime Directive in medicine relates to the concept of Therapeutic Index (TI). TI = Benefits from Treatment ÷ Adverse Effects of Treatment. The goal, therefore, is to improve the patient’s outcome while optimizing quality of life. The “benefits from treatment” in the context of cancer care are to cure the patient of cancer, and if this is not achieved then to extend the patient’s duration of life as much as possible, while maintaining quality of life. Additional benefits should also include ways to best utilize our health care dollars rather than waste them. Bing Crosby & the Andrew’s Sisters sang about this concept almost 70 years ago when they said: “You gotta accentuate the positive & eliminate the negative, and that’s what it’s all about.”

How do we do this with our prostate cancer patients? The answer lies in looking for ways to make all of our therapies more effective. We know that combination therapies address the multifaceted behavior of cancer far better than single agent therapy (monotherapy). Combination therapies also open the door to the possibility of synergism between drugs—both conventional anti-cancer drugs & others that function through various mechanisms e.g. signal transduction, apoptosis, anti-angiogenesis, etc.

There are a significant number of relatively non-toxic agents that are able to enhance the effectiveness drugs with known activity in PC. Are we using them—rarely, if ever. This talk will discuss these low impact pharmaceuticals, how they work, what drugs they work with, and the mechanisms of action and results of any preclinical or clinical data. This talk will review agents such as valproic acid, Avodart & Proscar, Dostinex & lisuride, calcitriol & DN101, Sulindac & Exisulind, ATRA & CRA, quinazolines, statins, PPAR-G agonists, and growth factor inhibitors like pentoxifylline.

Saturday Afternoon: Intermediate Risk Disease

1:30 Robotic Surgery
Mark H. Kawachi, M.D., F.A.C.S.

Robotic Assisted Laparoscopic Prostatectomy has become a very important treatment option for men with localized prostate cancer. This procedure has demonstrated advantages in faster recovery, less pain, and lower rates of blood transfusions when compared to traditional radical prostatectomy. In addition, this procedure promises the possibility of superior cure rates, faster return of continence, and more confident preservation of erectile function. This session will demonstrate not only the technology of robotic surgery (with live video footage), it will also help men separate hype from reality as the difficult process of selecting the best method for treating their disease.

2:15 IMRT/Brachytherapy (Radioactive Seeds)
Christopher M. Rose, M.D.

Patients with prostate cancer and no evidence of metastatic disease have a number of options in the management of the primary prostate tumor. Both surgical and radiological management have made great strides in the past decade. Advances in MR and CT imaging technology have provided unequivocal localization of the prostate gland, seminal vesicles, and associated lymph nodes. Now radiation can be deposited directly in the vicinity of the tumor bearing structures while limiting the dose to the surrounding bladder and rectum. Intensity modulation of the external radiation (IMRT) is a method of dividing a single radiation beam into a series of “beamlets” so that the dose of radiation to healthy tissues is reduced. In this way, sensitive organs like the rectum, bladder and small intestine will receive much less dose than the tumor itself. Computers can now aim multiple beams of radiation angled in from all around the patient so that the dose of radiation focuses to conform to the “kidney bean” shape of the prostate while keeping radiation away from the middle and posterior portions of the rectum and the anterior portion of the bladder.

Imaging the prostate in real time has further improved targeting. The patient is relocated immediately before, or during treatment to allow for prostate movement (from bladder and rectal filling or the passage of rectal gas). This latter process is called “Image Guided Radiation Therapy,” or IGRT. IGRT further enhances the accuracy of IMRT. This improved accuracy allows doctors to tighten the borders of the radiation field, further minimizing radiation exposure to the surrounding normal tissue.

One of the leading radiation therapy centers in the world, the group from Memorial Sloan Kettering Hospital in New York, has recently published the results of their 8-year experience with this IMRT. The cancer survival rates for favorable, intermediate and unfavorable risk cases were 100%, 96% and 84%, respectively. Despite their using extremely high radiation doses (in many cases surpassing 8,000 rads) the incidence of severe rectal bleeding was held to less than 2%.

While IMRT with IGRT results in significant dose shaping and adaptation for inadvertent motion, brachytherapy (the use of permanent and temporary radiation sources implanted directly into the prostate under direct real time ultrasound or MRI guidance) represents absolute conformality and the ultimate form of motion management. The radiation oncologist’s aim is to place multiple radiation sources directly into the prostate so that when the dose from each source is summated the resultant dose distribution conforms precisely to the tissue within the capsule of the prostate plus a margin of 3 mm. Since the dose tends to summate towards the center from the periphery there is a tendency to overdose the central urethra unless the sources are placed more towards the outside edge of the prostate gland. The development of a peripheral loading technique as well as computer algorithms that can run on powerful laptop computers that are brought into the operating room have provided radiation oncologists a way to do real time intraoperative planning and place sources in a sequential and differential manner, building up the dose to the entire gland while not overdosing or underdosing regions. Because the treatment is localized directly within the gland without treatment to the seminal vesicles or nodes, radiation oncologists use predictive artificial intelligence equations to restrict the treatment to patients not likely to have spread beyond the prostate. In the past year, two groups have published 12 and 15 year data showing absolute equivalence to the best surgical results with long-term PSA control rates of 89, 80, and 68% for low, intermediate, and high risk patients with a 93% cause specific survival for the entire cohort of patients.

3:30 Focal Cryotherapy
Duke K. Bahn, M.D.

Focal prostate cryoablation is partial freezing of the gland in patients whose prostate cancer is unilateral. . The tumor is ablated, whereas the contralateral prostate tissue and surrounding structures are spared. This method offers targeted cancer control while at the same time reducing the risk of losing sexual potency and urinary continence. Recent studies indicate that focal cryoablation may be more effective than bilateral nerve-sparing prostatectomy in preserving potency in appropriately selected patients. By offering a better chance for maintaining sexual function and urinary continence, in addition to achieving effective cancer control, focal cryoablation may be a good compromise for those who are not comfortable with either the less aggressive, watchful waiting approach, or more aggressive treatment with surgery or radiation.

4:00 Primary Intermittent Testosterone Deprivation
& supportive care with Aranesp & Zometa
Stephen B. Strum, M.D.

RP & RT are the primary therapies most often used in the treatment of PC. Treatment with primary ADT (androgen deprivation therapy) is rarely discussed or considered. However, several strong arguments can be made in favor of initial treatment with primary ADT.

1. The New England Journal of Medicine has reported that surgery (and presumably radiation) only improves 10-year survival rates by 5% compared to no treatment at all.
2. ADT is the only primary treatment that has a therapeutic effect on microscopic metastasis, the cancer cells that may have already spread outside the prostate.
3. Unlike surgery and radiation, the side effects of ADT are generally reversible.
4. Starting treatment with ADT, rather than surgery or radiation, suppresses cancer growth while opening up the possibility for a future yet-to-be-discovered treatments that will be less toxic.
The importance of enhancing Therapeutic Index by understanding how the side effects of ADT can be minimized (bone resorption, insulin resistance,, vitamin D and omega 3 fatty acid deficiencies, obesity, hyperlipidemia & anemia) will be reviewed. This talk will help men undergoing ADT to maximize their chance of a successful treatment outcome. Results of the clinical research on ADT that has evolved at Prostate Oncology Specialists via Drs. Strum, Scholz & Lam will be presented. The optimal way to use Intermittent ADT and the associated supportive measures that are needed will be discussed.

Gala Dinner:
Technology in Revolution
Donald S. Coffey, Ph.D.

Dr. Coffey has been the premiere research scientist in prostate cancer for several decades. He has trained (or influenced) most of those who have discovered advances in the understanding and treatment of the disease. He will recount some of the leading developments that have contributed to our knowledge base and impacted the current treatment of the disease. He will also discuss recent developments that he believes will change the prevention and treatment options in the future. This is a “Don’t miss!” talk that attendees will find insightful and entertaining. The impact it will have on your outlook on life is well-worth the cost of the dinner.

September 9, 2007

Sunday Morning: Management of Aggressive Prostate Cancer

8:30 Cardiac Issues for Prostate Cancer Patients
Matthew J. Budoff, M.D.

Statistics show that men with prostate cancer are far more likely to die from heart disease than from prostate cancer. Preventive strategies to prevent heart attacks are most effective when the disease is diagnosed at an early stage. Cardiac computed tomography is rapidly gaining popularity among cardiac experts for identifying patients with early deposition of plaque in their coronary arteries. Coronary artery calcium is the earliest detectable form of heart disease. It is present long before advanced blockage shows up and starts impairing blood flow to the heart. The “calcium scan” is a simple non-invasive test that allows measurement of the plaque building up in the heart. The ability to detect coronary artery calcification allows physicians to implement lifestyle changes and start effective medications at an early stage so that progression to overt symptomatic heart disease can be prevented.

For patients with known heart disease (previous heart attack, stent placement, bypass surgery), or patients simply with advanced degrees of coronary calcification, further scanning can be performed for a more in-depth evaluation of the coronary arteries to determine if the plaque is beginning to cause partial blockage. A measure of the degree of blockage can be obtained by doing a “Virtual Angiograms.” This procedure is performed by injecting contrast dye into a small vein in the arm during the scan procedure. The images obtained enable the physician reading the scan to visualize the inner contour of the arteries. This technology also enables “soft” (non-calcified) plaque to be detected. Bypass grafts, stents, and heavily calcified arteries can also be evaluated with a virtual angiogram.

9:00 Adjuvant Chemotherapy and Taxotere Combinations
Avastin, DN-101, Samarium, Neulasta, Aranesp
Richard Y. Lam, M.D.

Taxotere (docetaxel) is the most effective chemotherapy agent in prostate cancer. Taxotere is also one of the most valuable agents for the treatment of breast, neck, gastrointestinal and lung cancer. As a result of two landmark phase III studies, Taxotere has become the foundational agent for treating androgen independent prostate cancer. However, despite these successes, science marches on. Studies now show that the good results that can be obtained with Taxotere alone can be further enhanced when Taxotere is used in combination with other active agents such as Carboplatin, Avastin, activated vitamin D (Rocaltrol), Thalidomide, and Quadramet. Management strategies to counter potential side effects and optimize quality of life will also be reviewed in this presentation. Finally, new data on Taxotere, used in earlier stage disease (i.e. adjuvant setting), will also be reviewed.

9:45 IMRT for Oligo-metastasis and Lymph nodes
Christopher M. Rose, M.D.

In my previous presentation the use of Intensity Modulated Radiation and Image Guided Radiation Therapies as technologies to deliver high doses of radiation to the prostate gland were reviewed. Unfortunately, despite screening methods to identify prostate cancer at its earliest localized stage, significant numbers of patients present with disease spread to lymph nodes or to solitary bone sites. Traditionally many physicians have responded to this situation with nihilism: “The disease is incurable, therefore my task is only to minimize medically induced toxicity, and attempt to maximize quality of life.” Other physicians are trying to identify innovative strategies using hormones, chemotherapy, immune therapies, nutrition, and localized radiation to treat small and intermediate volumes of metastatic disease in an attempt to maximize both quantity and quality of disease.

In the past few years a number of different lines of research have suggested that there are waves of metastatic dissemination of cancer and that treatment of both the primary and limited numbers of metastatic sites may allow for both long-term survival and good quality of life. We will review this data on the natural history of oligometastases in prostate and other malignancies. We will also provide information on the use of IMRT and IGRT with innovative imaging to treat lymph nodes and small numbers of bony metastases with the same technology that is used to target localized prostate cancer. Although proof of the value of treating of node positive prostate cancer is circumstantial, we will review the data so that patients can opt for treatment or observation with informed choice.

10:30 Oral Agents:
Satraplatin, Thalidomide, (Revlimid), Nilutamide,
Phenylbutarate, Estrogens, Ketoconazole
Charles “Snuffy” Myers, M.D.

We have seen a sudden increase in the number of oral agents available or in development for the treatment of prostate cancer. Why do we have this change? In part, some of these drugs work by mechanisms that require the drug to be present continuously. This is possible with an oral drug, but not so for intravenous drugs. A second change has been an alteration in the way Medicare pays for cancer treatment. In the past, Medicare’s approach meant that a physician could give intravenous chemotherapy and other agents with a reasonable expectation that costs would be covered and that there might be a modest profit. This is no longer the case. Now, it is possible for a physician that Medicare may not cover the costs of administering an intravenous drug and might actually lose money. An oral drug offers a treatment option that does not pose such a threat.

Oral drugs for prostate cancer that are available or in development attack the cancer in one of several ways.

1) Antiangiogenesis: Since the drive for new blood vessel formation, it is also advantageous to have blockade of angiogenesis continuous. Celebrex at high doses has an antiangiogenesis effect that is mild in nature. Sutent is much more active and blocks VEGF, the major protein controlling angiogenesis in patients. The first clinical trials testing its use are now being reported and show promising results.

2) Differentiation Inducers: These drugs work by forcing the cancer back toward more normal behavior. This translates into slower cancer growth and less of a chance for metastatic spread. Again, these agents must be present continuously to work. Phenylbutyrate and phenylacetate have been known to work in this fashion for about 10 years. Both drugs must be taken in very high doses (greater than 20 grams a day) and cause gastric distress. Depakote is widely available and used to treat seizures. Early laboratory studies are promising and the first clinical study done at Johns Hopkins looks promising. Much more potent drugs are in development or early clinical trial testing.

3) Immune modulators: Thalidomide has long been used to improve immunologic function in AIDS patients. Early clinical trials suggest a rather dramatic synergy between thalidomide and Leukine, an injectable drug that also stimulates the immune system. Revlimid is a new and improved thalidomide with fewer side effects and greater anticancer activity. Anecdotal evidence shows potentially dramatic and rapid tumor responses.

4) Second line hormonal therapy: Ketoconazole and the antiandrogens (Casodex, Eulexin and nilutamide) are all active agents that either block the androgen receptor or block adrenal production of testosterone precursors.

5) Oral Chemotherapy: Satraplatin is a new platinum-based drug that is given orally and shows promising activity in patients who fail Taxotere.

11:15 Harnessing the Immune system:
Leukine®, anti-CTLA4, Dendritic cells, Low dose cyclophosphamide
William Cavanagh

The immune system functions throughout many decades of our lives to successfully clear cancerous cells from the body through a process known as “immune surveillance”. The development of human cancers, especially those that progress and metastasize, clearly reflects a breakdown of this function of the immune system.

Recent evidence indicates that successful immunotherapy of cancer requires not only the stimulation of the cytotoxic immune system – for instance through vaccine and cytokine therapy – but also a targeted depletion of the “regulatory” immune system. While the regulatory immune system in the healthy individual functions to protect “self” tissues from attack by an overactive immune system, in the cancer patient, an overregulated immune system may also be protecting the cancer from immune attack. Modulation of the regulatory immune system will be the main subject of this presentation. Active agents that modulate the “regulatory” immune system that are presently on the market (Leukine®, Low-dose Cyclophosphamide), or are in the late stages of developmental research (dendritic cells, CTLA-4), will be discussed in this talk.

Sunday Afternoon: What’s in Store for the Future

1:30 Exciting New Agents in the Research Pipeline
Howard Soule, Ph.D.

Major advances in technology have propelled the biological understanding of cancer to unprecedented levels. Laboratories all over the world, academic, government, and industrial, are working to apply these new finding to discovery of new medications that will fight cancer. Many of these new experimental medications are heralded by the new discipline of predictive medicine: physicians will treat cancer as a single disease and tailor treatments by these molecularly-defined signatures.

A significant effort in prostate cancer drug discovery and development is underway. These activities range from the early pre-clinical status to large, randomized, FDA registrational Phase III clinical trials. This presentation will review some of these very encouraging and hopeful developments.

2:30 Multi-Disciplinary Round Table with Case
Presentations and Questions from the Audience
Duke Bahn, Stan Brosman, Bill Cavanagh, Richard Lam, Snuffy Myers, Chris Rose, Mark Scholz, Stephen Strum

Treatments to be Discussed: Zometa, Samarium, Avastin, Thalidomide, Taxotere, Revlimid, Taxol, Carboplatin, Abraxane, Dendritic Cells, Neulasta, Growth Factorm Inhibitors, Satraplatin, Aranesp, Others

 

 

Prostate Cancer Research Institute (PCRI)

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