Condition Spotlight: Treating Castrate Resistant (Advanced) Prostate Cancer Richard Augspurger, M.D., F.A.C.S.

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1 Issue 12 Winter 2013 Condition Spotlight: Treating Castrate Resistant (Advanced) Prostate Cancer Richard Augspurger, M.D., F.A.C.S. When I first began practicing urology in the late 1970s, our treatment options for prostate cancer were limited to surgery or radiation for localized disease and hormone therapy (today referred to as androgen deprivation therapy) for advanced prostate cancer. Once a patient with advanced, or castrate resistant, prostate cancer failed to respond to hormone therapy, urologists did not have much more to offer other than palliative care. There were no significant changes in the management of advanced prostate cancer over the next 25 years until That year, a chemotherapeutic agent, docetaxel, was shown to increase survival in men with advanced prostate cancer by two months. This was the first study that showed any real benefit in using chemotherapy to treat prostate cancer, not to mention the benefit it could potentially provide advanced prostate cancer patients. Since the docetaxel study was published in 2004 there has been significant progress in understanding the cellular physiology of prostate cancer cells, what changes they undergo to become castrate resistant and how best to attack those cells. Urologists have a better understanding of bone physiology and as a result we have witnessed multiple new agents developed and approved for the treatment of castrate resistant prostate cancer over the past few years. Each of these agents has improved survival by two times greater than the initial survival advantage demonstrated for docetaxel. These agents fall into several different categories: Immunotherapy - Sipuleucel-T, Provenge: Immunotherapy works by stimulating a patient s own immune system to attack prostate cancer cells. Blood cells are removed from the body during this process, similar to giving a unit of blood. In the laboratory the cells are activated to attack prostate cancer cells. Then the activated blood cells are given back to the patient, like a transfusion, to stimulate his own cells to attack the prostate cancer cells. Chemotherapeutic agents: There is a new agent on the market, cabazitaxel, which has been shown to be effective for patients who have failed docetaxel. Both drugs require the use of prednisone along with chemotherapy. Hormonal manipulation: The majority of agents in use today such as Lupron (leuprolide acetate) are receptor agonist. These agents mimic normal hormonal agents to block the production of hormones, but at times can stimulate the production of testosterone. A newer class of antagonist agents such as Firmagon (degarelix), just block the receptor and do not stimulate hormone production. These antagonists keep testosterone suppressed, unlike the significant small spikes that sometimes occur between injections in patients on agonists. Androgen Deprivation - CYP-17 agents: These agents are different from most commonly used agonists. They work by blocking not only the production of testosterone by the testicles, but also the adrenal gland. An older agent is ketoconazole. The Continued on page 2

2 Castrate Resistant (Advanced) Prostate Cancer (cont.) newer agent is Zytiga (abiraterone). When these agents are administered patients must also be on steroidal medications to block some of the side effects. Zytiga was recently approved for use prior to chemotherapy. Antiandrogens: These agents work by blocking the uptake of testosterone into the cells. The most commonly recognized antiandrogen is Casodex (biclutamide). A newer agent is a super antiandrogen Xtandi (enzalutamide) which was recently approved by the FDA. An important aspect of the management of advanced prostate cancer is a patient s bone health. At TUCC, our androgen deprivation therapy clinic monitors the treatment and side effects associated with advanced prostate cancer. We try to be proactive to prevent side effects by placing patients on calcium and vitamin D. There are two agents available that block bone disintegration. Zometa (zoledronic acid) is a bisphosphonate that binds to the bones and prevents the cellular initiation of bone breakdown. The second is Xgeva or Prolia (denosumab) that works by blocking the breakdown of bones though a different pathway. With all of these newer agents, urologists don t often see a PSA response to be able to predict the long-term outcome of the therapy. Typically, it is how a patient is feeling and overall mortality rates that predict the success of the treatment. I expect that many new agents will continue to be tested and approved by the FDA for the treatment of advanced prostate cancer based on the success we ve seen since docetaxel was first studied in For more information on the treatment of advanced prostate cancer, please visit Treatment Taken to the Next Level TUCC Tumor Board Eric Gross, M.D. Each month, TUCC sponsors a multidisciplinary tumor management conference comprised of physicians representing urology, radiation oncology, medical oncology, radiology and pathology. Patient cases are presented to this panel with a comprehensive review of history and physical exam findings, clinical labs, imaging and first-hand assessment of pathologic specimens gathered from biopsy or surgery. The tumor board reviews both straight-forward and complex cases. Many require a multi-disciplinary approach to treatment. Patients being reviewed are also assessed for potential enrollment in clinical trials, many of which are offered through the TUCC Clinical Research Department. The decisions of the TUCC tumor board are based on national guidelines. Participating physicians receive continuing medical education (CME) credit required for board certification. This is an open conference, meaning any physician or provider can present a urologic case. If a TUCC patient is interested in having their case reviewed, please direct inquiries to Dr. Gross in the TUCC Radiation Oncology Department. 2 TUCC In Focus Issue 12, Winter 2013

3 Radiation Therapy vs. CyberKnife What s the Difference? Over the past year, there has been a lot of advertising and marketing promoting CyberKnife as a treatment option for prostate cancer. Presently, there are three CyberKnife machines in use in metro Denver. CyberKnife is a form of external beam radiation that utilizes photons (x-rays). Originally, CyberKnife was designed and approved for treatment of tumors involving the brain and those along the spinal cord. Typically, these types of tumors are treated with very large doses per session (fraction) for 1-5 sessions. Use of CyberKnife in other areas of the body has been explored in recent years, including the prostate. Since CyberKnife is only reimbursed by insurance companies for a maximum of five sessions, attempts have been made to determine its proper daily dose for prostate cancer treatment. The standard prostate cancer radiation therapy regiment is sessions. With CyberKnife, a very large dose must be given to prostate cancer patients each day in order to administer the biologic equivalent dose of traditional radiation treatments. Formulas utilizing ill-defined variables, as well as extrapolations from high-dose rate brachytherapy doses, have been used to try to identify the proper dosing regimen for CyberKnife. Presently, there are no long-term studies which have evaluated CyberKnife as a treatment for prostate cancer. Five-year data from a study done at Stanford University have been published. Patients in that study were required to be low risk prostate cancer patients. Preliminary results of the study revealed that for this specific subset of patients, CyberKnife may be as effective as traditional external beam radiation therapy. Thus far, there does not appear to be any increased side effects. However, the question is whether these results, in terms of outcome and side effects, will hold up over longer periods of time. The results need to be confirmed in a larger prospective multi-institution study trial. What do we know in 2013? No studies have shown an improved outcome (cure rate) with CyberKnife treatments. No studies have shown a decreased side effect profile with CyberKnife treatments. Large daily doses may lead to more long-term side effect issues - more data is needed before we know the answer to this question. The treatment length is shortened to five days because of reimbursement issues, not because of better outcomes or fewer side effects. Presently, only low risk prostate cancer patients should be treated with CyberKnife as a monotherapy, preferably under a study protocol. For more information on radiation therapy treatment options for prostate cancer, please visit Issue 12, Winter 2013 TUCC In Focus 3

4 TUCC Performs the Most Robotic Prostatectomies in the Rocky Mountain Region The first robotic prostatectomy was performed in the U.S. in November 2000 and over the past decade the procedure has grown to become the top treatment choice for localized prostate cancer in the country. There are many benefits to robotic surgery for patients including shorter hospital stays, quicker recovery times, less pain and decreased blood loss. At TUCC, our six robotic surgeons are among the most experienced robotic surgeons in the country. TUCC is a founding physician partner of the Porter Robotics Institute (PRI) at Porter Adventist Hospital. According to a report issued by Intuitive Surgical in December 2012, the PRI is the fastest growing robotic surgery program for prostate cancer in the Rocky Mountain region. In 2012 alone, TUCC performed over 250 robotic prostatectomies. We re proud to have performed more robotic prostatectomies than any other facility in the region last year. Since 2006, TUCC surgeons have performed more than 1,800 robotic prostatectomies in Colorado. The TUCC robotic surgeons photographed at our center. What s important for our patients and referring providers to know is that the PRI is more than just a robot. Our nationally renowned surgeons offer patients access to the latest technology for their surgeries through the da Vinci Si surgical robot. Our OR team is dedicated solely to robotic procedures which ensures consistency in the quality of care delivered to patients. And, we track each patient s journey from preoperative planning to postoperative care to see how we might be able to improve their results. At the PRI, TUCC is working to revolutionize the patient experience. Visit to learn more about TUCC s robotic surgery expertise and our partnership with the PRI. Save the Date! Attention Colorado men: Now s the time to learn what you need to look for to not only keep you in the game, but at your best. Join TUCC Foundation for the first annual Men s Health Challenge on Saturday, May 18, This event is the first of its kind in Denver. It includes a free men s health screening for prostate cancer, low testosterone, glucose and cholesterol, blood pressure, body mass index, nutritional assessments and much more. Throughout the day, local and national health experts will lead 10-minute informational sessions on acupuncture/complementary medicine, cancer prevention, heart health, prostate issues, male sexual health, male fertility, smoke cessation, exercise and sports health. Resources on wills, estate planning and other financial issues will also be available. Be sure to stick around for a special halftime presentation and surprise celebrity guests at 12:00 p.m. Giveaway bags will be provided to every participant and special offers will be raffled off throughout the day. Join us and fight like a man for men s health! when: Saturday, May 18, :00 a.m. 4:00 p.m. where: cost: PPA Event Center 2105 Decatur Street Denver, CO Free parking will be available in the main PPA parking lot. FREE Visit to learn more. 4 TUCC In Focus Issue 12, Winter 2013

5 2013 Patient Support Groups Each month, TUCC hosts free patient support groups for bladder, kidney and prostate cancer patients in our third floor conference room. Support group sessions alternate between presentations from urologists or other medical professionals and open discussions. All sessions are also open to patients being treated outside of TUCC. This year, TUCC will host two new groups that alternate monthly. Our prostate cancer support group for Spanish speaking patients will begin in January and the friends and family support group will hold its first meeting in February. Monthly Support Groups Prostate Cancer January / February / March 412:00 p.m., 3rd Thursday of the month April / May / July / August 46:00 p.m., 3rd Thursday of the month Bladder Cancer January / February / March 412:00 p.m., 4th Tuesday of the month April / May / July / August 46:00 p.m., 4th Tuesday of the month Kidney Cancer January / February / March April / May / July / August 46:00 p.m., 4th Thursday of the month Prostate Cancer (Spanish) January / March 412:00 p.m., 2nd Wednesday of the month May / August 46:00 p.m., 2nd Wednesday of the month Friends & Family February 412:00 p.m., 2nd Wednesday of the month April / July 46:00 p.m., 2nd Wednesday of the month Annual Events In addition to monthly meetings, TUCC support group attendees are able to participate in a variety of educational activities each year. Save the date for these important activities in 2013: Interstitial Cystitis Symposium 4Saturday, May 11, 8:30 a.m. Men s Health Challenge 4Saturday, May 18, 9:00 a.m. 4:00 p.m. Annual Patient Survivorship Picnic 4Sunday, June 2, 1:00 3:00 p.m. The Blue Shoe Run for Prostate Cancer 4Saturday, September 14, 8:00 a.m. Annual Presentation on Nutrition & Supplements with Dr. Mark Moyad 4Thursday, October 24, 7:00 p.m. Holidays & Cancer 4November 13, 12:00 p.m. Visit or call to register for an upcoming session. Issue 12, Winter 2013 TUCC In Focus 5

6 Advancing urologic care in the Rocky Mountain region through advocacy, research, education and support. TUCC Foundation 2012 Highlights Throughout 2012, TUCC Foundation, a 501 (c)(3) non-profit charity, reached thousands of Coloradans through prostate and bladder cancer screenings, urologic health seminars and the annual Blue Shoe Run for Prostate Cancer. TUCC Foundation includes five overarching funds: Community Outreach Fund, Educational Outreach Fund, Employee Emergency Fund, Patient Assistance Fund and the Research Fund. In 2012, we provided $12,000 of assistance to urologic patients in need. Through our Medical Education Scholarship Program, TUCC Foundation distributed $2,000 to the Denver School of Nursing. Also in 2012, TUCC Foundation made a $20,000 donation through our Research Fund to the American Cancer Society to help fund a research grant for the study of metastatic prostate cancer at the Albert Einstein College of Medicine. TUCC Foundation organized and participated in several high profile community events last year including the Center for African American Health s Annual Health Fair in February and the Centro San Juan Diego Family Health Fair in November. In October 2012, Mark Moyad, M.D., director of complementary medicine at the University of Michigan, returned to Colorado for his 15th presentation on nutrition and supplements. More than 250 people joined TUCC Foundation for this premier event. The Blue Shoe Run for Prostate Cancer TUCC Foundation s signature fundraising event is The Blue Shoe Run for Prostate Cancer, a 5K run/walk, 1.5-mile family walk and kids fun run taking place on the north side of Sports Authority Field. On Saturday, September 8th, more than 1,000 people joined TUCC Foundation for the third annual Blue Shoe Run. This tremendous participation resulted in more than $125,000 raised for the Foundation s work in the Rocky Mountain region.

7 Current Clinical Trials TUCC is now enrolling patients in the following clinical trials: Bladder Cancer A Phase II, open-label study evaluating DN24-02 as adjuvant therapy in subjects with high risk HER2+ urothelial carcinoma. This study incorporates a novel immunotherapy given intravenously. The Blue Shoe Run By the Numbers Over 1,000 participants (an almost 40 percent increase from our first race in 2010)! 21 Blue Shoe Run teams. Three Denver-based bands entertaining those on the course and others during the post-race party. A lively post-race party led by 7News Anchor Mike Landess and former Denver Mayor Frederico Pena. More than $10,000 raised during the second annual Blue Shoe Run silent auction. 48 community and corporate sponsors. Approximately $100,000 worth of online, radio and television media donated to promote The Blue Shoe Run. More than 3,000 Colorado men are diagnosed with prostate cancer every year. The disease is the most commonly diagnosed cancer in the state today. Because of the continued success of The Blue Shoe Run, Coloradans are well on their way toward stomping out prostate cancer. Approximately $275,000 has been raised through participation and donations for over the past three years. But our work isn t done yet. We invite you to put on your blue shoes and run for your father, your brother, your husband or your friends at the fourth annual Blue Shoe Run for Prostate Cancer on Saturday, September 14, 2013! Together, we can grow The Blue Shoe Run into the largest prostate cancer benefit race in the country. Online registration for 4th annual Blue Shoe Run for Prostate Cancer will open on March 1, Who are you running for? TheBlueShoeRun.com A Phase II, randomized, open label, parallel ARM study to evaluate the safety and efficacy of rad-ifn/syn 3 following intravesical administration in subjects with high grade, BCG refractory or relapsed non-muscle invasive bladder cancer. This research study evaluates the effectiveness and safety of two doses of Instiladrin given into the bladder on up to four occasions. Prostate Cancer A Phase II study of abiraterone acetate plus prednisone in subjects with advanced prostate cancer without radiographic evidence of metastatic disease. This approved medication will be studied to possibly offset the progression of non-metastatic prostate cancer in patients currently on hormonal therapy with a rising PSA. A Phase II efficacy and safety study of MDV3100 vs. bicalutamide in castrate men with metastatic prostate cancer. Study to evaluate new or worsening lens opacifications in subjects with non-metastatic prostate cancer receiving denosumab for bone loss due to androgen deprivation therapy. This is a clinical trial that incorporates an approved bone loss prevention medication. An international, open label, randomized study assessing the safety and efficacy of a monthly dosing regimen of ozarelix vs. goserlin depot (Zoladex) in men with prostate cancer. Men must be 45 years of age or older and have not had any previous hormonal therapy. A Phase II multi-center prospective open label, 2-dose level clinical trial studying the safety and efficacy of an injection of NX-1207 for the treatment of low risk, localized (T1c) prostate cancer. An open, non-randomized, uncontrolled, multiple dose escalation study of the safety and effectiveness of an investigational drug (ODM-201) for men with advanced prostate cancer. A Phase II, double blind, efficacy and safety study of enzalutamide vs. bicalutamide in men with prostate cancer who have failed primary androgen deprivation therapy. Issue 12, Winter 2013 TUCC In Focus 7

8 Current Clinical Trials (cont.) Prostate Cancer (cont.) A randomized, double-blind, Phase III efficacy trial of PROSTVAC-V/F +/- GM-CSF in men with asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer. Patients must have a progression of their prostate cancer during hormonal therapy. Patients cannot have metastatic disease to any other organ than lymph nodes and/or bone and must not have received previous immunotherapy or chemotherapy for prostate cancer. Kidney Cancer An international Phase III randomized trial of autologous dendritic cell immunotherapy (AGS-003) plus standard treatment of advanced renal cell carcinoma. Urinary Incontinence A Phase IV, placebo controlled study to evaluate the efficacy and safety of VESIcare to improve urinary incontinence in men after robotic assisted radical prostatectomy. Patients must be experiencing urinary incontinence (requiring 2-10 pads a day) for seven days consecutively after urinary catheter has been removed. Cannot be taking OAB medications currently. For all patients: Participation in clinical research is voluntary. Your voluntary participation can be withdrawn at any time and study withdrawal will not impact your treatment at TUCC. When participating in a clinical trial at TUCC, you will receive study procedures, study medication and study related care at no cost to you. For more information, please visit or call Mile High Stadium Circle Denver, CO 80211