Take One! PROSTATE CANCER COMMUNICATION VOLUME 30, NUMBER 1 • SPRING 2014 FOUNDER: LLOYD J. NEY, SR. FOUNDED 1984 Inside this Issue: Male Lumpectomy: Focal Therapy is the Future of Prostate Cancer Treatment Treatment Options for Post-Prostatectomy Incontinence What the Heck Has Been Going On In My World Challenging PC Treatment Biases – Is Nothing Sacred? Be sure to visit our new website at: www.paactusa.org We now offer the convenience of making donations online! Life Without Prostate Cancer: Imagine The Possibilities! TABLE OF CONTENTS Bonus Book............................................................................................. 2 Conference – September 5-7, 2014........................................................... 2 Los Angeles, CA PROSTATE CANCER COMMUNICATION Published Quarterly by: PAACT, Inc. Patient Advocates for Advanced Cancer Treatments 1143 Parmelee NW Grand Rapids, MI 49504 President…Richard H. Profit Jr. Editors….Richard H. Profit Jr./Molly Meyers Staff….Molly Meyers David Sochacki Webmaster….Omega Systems Male Lumpectomy: Focal Therapy is the Future of Prostate Cancer Treatment....................................................................... 3 By Gary Onik, MD Treatment Options for Post-Prostatectomy Incontinence........................... 7 By Gary E Leach, MD What the Heck Has Been Going On In My World - Part 64........................... 10 By Mark A Moyad, MD, MPH Challenging PC Treatment Biases – Is Nothing Sacred? Part 2................... 17 By Robert (Dr. Bob) Leibowitz, MD Acknowledgements............................................................................... 22 PAACT Membership Form........................................................................ 24 Postmaster: Send address changes to: Prostate Cancer Communication P.O. Box 141695 Grand Rapids, MI 49514 Phone: 616/453-1477 Fax: 616/453-1846 E-Mail: paact@paactusa.org PAACT Web Page: http://www.paactusa.org Newsletter: http://www.paactusa.org EDITOR: Articles authored by other than the editor may not fully reflect the views of the corporation but are printed with the understanding that the patient has the right to make his own interpretation of the efficacy of the information provided. In an effort to conserve space and be able to insert as much material as possible in the newsletter, references from various articles are intentionally omitted. If you would like to obtain those references, please contact PAACT, we keep all of the original articles and the references used on file. President and Chairperson: Medical Advisory Board: Richard H. Profit, Jr. Board of Directors: Richard J. Ablin, Ph.D. V. Elayne Arterbery, M.D. Robert A. Badalament, M.D. Duke K. Bahn, M.D. Israel Barken, M.D. E. Roy Berger, M.D., F.A.C.P. Douglas O. Chinn, M.D. Michael J. Dattoli, M.D. Fernand Labrie, M.D. Gary E. Leach, M.D. Fred Lee, Sr., M.D. Robert Leibowitz, M.D. Mark A. Moyad, M.D., M.P.H. Charles E. Myers, Jr., M.D. Haakon Ragde, M.D. Oliver Sartor, M.D. Stephen B. Strum, M.D., F.A.C.P. Ashutosh (Ash) K. Tewari, M.D., M.CH. Donald L. Trump, M.D. Newton Dilley Saleem Durvesh, Executive Marketing Director Edwin Kuberski, Treasurer Janet Ney, Director Janette Ney, Director Anthony Staicer, Director Honorary Board Members: A.W. (Bud) Irish Russell Osbun Art Schlefstein Produced By: BONUS BOOK! With each donation we will send you one of DONALD KALTENBACH’S prostate cancer books: “PROSTATE CANCER ARMED & READY: A SURVIVAL GUIDE TO DIAGNOSIS, TREATMENT AND RECOVERY.” Foreword by John Blasko, MD University of Washington, Seattle, WA Clinical Professor - Radiation Oncology MALE LUMPECTOMY: FOCAL THERAPY IS THE FUTURE OF PROSTATE CANCER TREATMENT GARY ONIK, MD • THE ONIK PROSTATE CANCER CENTER - AVENTURA, FL CONTACT: KAREN BARRIE, MS (847) 502-1414 OR EMAIL: BARRIEMEDMARKETING@GMAIL.COM INTRODUCTION For both patients and doctors, current prostate cancer management reminds me of Oliver Hardy saying to Stan Laurel, “This is another fine mess you have gotten me into!” Relying on radical treatments with high morbidity, we seem to have abandoned the basic tenets of cancer therapy: 1. Find it early. 2. Stage it as accurately as possible. 3. Treat it aggressively, appropriate to its stage and tumor aggressiveness. We find ourselves in a paradoxical situation. Early detection of prostate cancer has become difficult, if not impossible, due to new guidelines against routine PSA screening. Why did the U.S. Preventive Services Task Force, a volunteer panel of medical professionals, rule against wide use of a simple and effective screening tool? First, men with suspicious or rising test results are sent for an unpleasant diagnostic procedure (TRUS biopsy) that has been proven to miss up to 30% of cancers. Those with negative biopsies later have repeat biopsies, while expense (and anxiety) mount up. Second, this protocol finds too many less aggressive cancers—and the cure may be worse than the disease. A dilemma between overtreatment vs. no treatment occurs when patients diagnosed with low-to-moderate risk cancer are counseled to defer treatment in favor of active surveillance, a strategy for which many patients don’t have the psychological tolerance—they worry that a time bomb is ticking in their bodies. This worry may well be justified by a recent UCLA study showing how prostate cancer cells are a moving target. (1) Yet this advice is given so men can hold off on the risks of overtreatment: urinary and sexual side effects. So we don’t go looking for cancer because we might find it, over treat it, and damage men’s quality of life? Can you think of any other cancer for which early detection is discouraged and treatment delayed? It is extremely rare to suggest that other cancers (breast, liver, lung, kidney, liver, etc.) can simply be monitored! My twofold thesis addresses this dilemma by offering a safe and effective middle ground: A.For diagnosis, there is an alternative to TRUS biopsy that is extraordinarily accurate, painless, and does not involve puncturing the rectal wall. It is the 3D Transperineal Prostate Mapping Biopsy (3D-PMB), which is more disease-specific for low, moderate and high-risk cancers than MRI-guided targeted biopsies. It improves prostate cancer management decisions by up to 70% because it allows matching the treatment to the disease, and it provides specific localization for precise targeting. In short, it meets the first and second tenets of cancer therapy. B. For treatment, there is an effective FDA-approved minimally invasive procedure that satisfies the third tenet of cancer therapy, to the major benefit of the patient. THE MALE LUMPECTOMY This article describes our latest results with both 3D-PMB and focal cryotherapy (cryoablation, or simply cryo, meaning lethal freeze). Our data validates the advantages of what I first termed the Male Lumpectomy. I now have long term results (average follow up of 10 years) with focal cryotherapy for prostate cancer or the Male Lumpectomy. I first presented this idea in a 2002 paper (2) demonstrating that we could effectively locate and target a prostate tumor without having to destroy, remove or irradiate the whole gland. By isolating and treating just the tumor and a surrounding safety margin, we generate competitive (actually better) efficacy in controlling cancer while preserving healthy tissue to markedly lower morbidity (side effects). That paper started the ball rolling. Focal prostate cancer therapy is now carried out in some manner in major U.S. cancer centers, including MD Anderson, Johns Hopkins, Sloan Kettering, Duke and NYU to name a few. Textbooks cover the subject and annual medical meetings on this topic are convened. The results are consistent: good cancer control, yet low side effect risks. My own study data offers compelling evidence that mapping biopsy and focal cryo provide a combined clinical approach www.paactusa.org • Spring 2014 / Prostate Cancer Communication 3 that completely changes the current paradigm, meeting the highest cancer treatment standards, and bringing it fully in line with the best therapies for local treatment of any other tumor. Additionally, this approach greatly reduces the high economic costs of conventional prostate cancer treatments (robotic prostatectomy and radiation therapy), as well as the long term personal quality of life costs (with their own associated management dollars). MATERIALS AND METHODS In our practice, we stage patients for focal therapy using 3D Transperineal Prostate Mapping Biopsy (3D-PMB). Transrectal ultrasound (TRUS) guided biopsy is not enough to guide focal therapy. 3D-PMB is carried out under general anesthesia (so it’s painless). Unlike a transrectal biopsy, which takes prostate samples through the rectal wall, 3D-PMB is done through the perineum (the skin between the scrotum and rectum). A grid, like that used in brachytherapy, is placed against the skin, and ultrasound guides the position of needles into the gland. Note that while ultrasound cannot distinguish important differences in normal and cancerous tissue, it clearly shows the placement of biopsy needles. Tissue samples taken throughout the gland are separately marked with the grid coordinates so their precise location is identified in the pathology report. This is what gives a threedimensional or holographic map of any cancers, even very small ones that might be found. We are able to take far more samples than the 10-12 commonly taken in a TRUS biopsy. 3D-PMB also has the advantage of more accurate Gleason scores since there’s little risk of missing a tumor core where the more dangerous cells tend to be. A study we published in the most prestigious cancer journal in the world (Journal of Clinical Oncology) compared the results of TRUS biopsy vs. 3D-PMB in over 180 patients (3). What we found was sobering. Compared to TRUS biopsy, 3D-PMB found 50% more cancer on the opposite side of the gland. It also raised the Gleason score in approximately 25% of patients. Additionally, a 3D-PMB is safer than TRUS biopsy because it is a sterile procedure, greatly lowering the chance for life threatening sepsis (infection with colon bacteria) and debilitating prostatitis that are significant risks in TRUS biopsy. Identifying the exact location of each specimen allows exact treatment targeting of the tumor, including its location, size and shape. Some clinicians are using MRI guided biopsies to guide focal therapy. Studies comparing MRI to mapping biopsy or prostatectomy specimens show that it misses 25% of significant cancers (4) and is only 28% specific, meaning that 72% of the time what it reads as cancer is not (5). While I support advanced multiparametric MRI of the prostate as an adjunct resource, only 3D-PMB can give the thorough tissue map necessary for long term cancer control as demonstrated by my data. 4 Prostate Cancer Communication / Spring 2014 • www.paactusa.org What about the concern that biopsies spread cancer? There is absolutely no credible clinical evidence that this happens. Why is this important? Fears of “track seeding” have been sadly overplayed by a handful of doctors who feed patients’ wishful thinking that prostate cancer can be clinically diagnosed and staged by imaging alone. In fact, MRI or color Doppler is not specific enough to make an accurate diagnosis of prostate cancer, meaning it often OVER estimates less aggressive cancer, and is not sensitive enough in identifying very small but significant cancers. Anyone who tells you, based solely on imaging, that you have cancer is doing you a great disservice—especially if they proceed to treat you. It is my conviction that any physician who treats based on imaging and/or rising PSA without biopsy confirmation is committing the grossest kind of malpractice. In the last month I encountered two patients who had been offered radiation without biopsy confirmation of cancer. I was appalled, as this violates the universal medical ethic, “Above all do no harm” (primum non nocere). In our practice, we originally theorized that perhaps 25-30% of prostate cancer cases would be amenable to focal therapy. Our experience, confirmed by another study (6), showed that as many as 94% of patients qualify for a focal approach. In other words, focal therapy is more than a “niche” treatment— many more men may benefit, especially when their disease is accurately diagnosed and staged, and when the treatment is done by an expert. Once you have located the tumor there are a number of ways to kill the cancer. We mainly use cryotherapy (cryoablation or simply “cryo”) to carry out the focal therapy. Cryo is the only ablation modality that has Level One evidence of superiority over beam radiation in eradicating cancer (compared in a randomized study) (7). Another excellent reason to use cryo comes from evidence of a specific tumor immunologic effect when a cancer is frozen. This effect has been shown in animal models to prevent metastatic disease and to cause regression of distant prostate cancer metastases (spread) in patients. Our cancer control results with medium and high risk patients are so much better than reported data with radical prostatectomy or radiation that an immunologic explanation for these results must be considered. Heat-based therapies such as laser and HIFU denature (destroy beyond recognition) tumor proteins (antigens). It is these antigens on the surface of cells that scatter into the body. Since they are not intact cells they cannot spread or cause cancer, but they are helpful because they appear to trigger this immunologic effect (8, 9). I predict it will take at least a decade to see if heatbased ablation gets the same immunologic results. Personally, I don’t want to deprive my patients of this potential benefit, particularly when there is no advantage I can see, as yet, to other ways of killing the tumor. FOCAL CRYO RESULTS In our practice, we now have clinical data on a total of 70 patients who underwent focal cryo. All have at least 8 years follow-up (ranging from 8 to 18 years with a mean follow up of 10.1 years). 41 patients were Gleason 6 or less, 24 were Gleason 7 (6 patients 4+3, 18 patients 3+4) and 5 were Gleason 8 or greater. 15 patients had a PSA of 10 or greater. We stratified the 70 patients using the D’Amico system. Thus, 29 patients were low risk, 32 medium risk, and 9 high risk. TABLE 1: PATIENT DEMOGRAPHICS Patients Follow-up 70 8-18 years Mean 10.1 years D’Amico Risk level Low 29 Medium 32 High 9 Gleason score Gleason 6 or less 41 Gleason 7 24 Gleason 8 or greater 5 Stage T1c 56 T2a 6 T2b 3 T2c 4 T4 1 PSA level at DX less than 10 54 10-20 13 greater than 20 2 Table 1. Risk stratification of patients treated with focal prostate cryoablation (N = 70) Overall actuarial survival was 66/70 (94%), meaning 4 patients died from other causes. Disease specific survival was 64/64(100%), meaning no patients died from prostate cancer. This is a rather remarkable statistic given that the majority of patients in this series (41) were medium to high risk. It certainly illustrates that patients who are appropriate candidates for focal therapy are not taking a greater risk of death in choosing this avenue. Overall Biochemical Disease Free Survival (BDFS, meaning no rise in PSA) was 89% (62/70). When broken down by risk level, BDFS for low risk patients was 90% (26/29), for medium risk patients 88% (28/32) and for high risk patients 89% (8/9). These again are rather remarkable results. For comparison, a 2012 article by Ginsburg, et al., looking at results of robotic radical prostatectomy with over 1100 patients had an overall BDSF of 72% at 5 years (10). See Table 2. TABLE 2: RESULTS Overall actuarial survival N=70 66/70 (94%) Disease specific survival N=70 70/70 (100%) Biochemical Disease Free Survival 62/70 (89%) BDFS High Risk (D’Amico) 8/9 (89%) BDFS Med Risk (D’Amico) 28/32 (88%) BDFS Low Risk (D’Amico) 26/29 (90%) Bilateral Multi focal 19/20 (95%) Local recurrence N=10 9/10 (90%) Continent after primary procedure 70/70 (100%) Retained potency 48/60 (80%) Table 2. Survival and recurrence rates for focal prostate cryoablation (N = 70) In my experience in a tertiary referral practice, having interviewed patients who have already seen surgeons, it is unusual to encounter a patient who has had explained to him what a “positive margin” is. For those who are unclear, after the gland is removed, the cut margins of the gland are stained and microscopically examined for tumor. If tumor is found at the cut margin the implication is that there is residual cancer left in the patient. This is called a positive margin. It leads to a high rate of disease progression. In Ginsburg’s study positive margins occurred in 27.3% of patients, which the authors describe as in keeping with national statistics. Our results, with selective tumor destruction while preserving healthy, functional prostate tissue, hold great promise for patients who might otherwise undergo surgery, with its risks of short and long term urinary and sexual side effects, only to experience a rising PSA within years of the treatment. Why all risk levels of patients would have the same cancer control results, might have two possible explanations: 1.Focal cryo has an ability to treat extracapsular disease. Patients at high risk for positive margins at prostatectomy have a better chance of local control with ablative therapy. This was very well illustrated by one of our patients who had a T4 lesion already invading the bladder, a PSA of 200 and a Gleason score of 10. He is now 8 years out from his cryo with no evidence for recurrence. We also have used a localized removal of urethral tissue in some patients who had tumor next to the urethra, when we were afraid that the urethral warmer might prevent a completely destructive freeze at that site. 2. A cryoimmunological response must also be considered for these remarkable results in medium and high risk patients. Based on the human and animal data, it’s likely that in some patients there is exposure of tumor antigens at the time of the www.paactusa.org • Spring 2014 / Prostate Cancer Communication 5 procedure that acts as an in vivo cancer vaccine, preventing later metastasis from occurring. A WORD ABOUT RECURRENCE Choosing radiation or RP as a first or primary treatment limits future options. Neither has a good fallback position should local disease recur. Hormone ablation is not curative, and the side effects are unpleasant. However, when focal cryo patients are retreated they do extremely well. The ability to retreat patients with local recurrences by repeat freezing, or even RP or radiation, means that our patients have less chance of untreated local residual cancer that can later spread. In our series, 10% of patients (7/70) were retreated with cryo to the opposite side of the original procedure. (In other words, a second cancer later occurred in previously biopsynegative and therefore untreated tissue.) All 7 (100%) are biochemical disease free (BDF). Two patients with local recurrence underwent radiation and both are BDF. One patient underwent RP and radiation and is now on ADT (hormone ablation). In total, 14% of patients (10/70) had a local recurrence that required re-treatment, and 90% of those 10 patients (9/10) remain BDF. Bilateral disease (cancer on both sides of the gland at initial treatment) was not a barrier to successful focal therapy. In our series, 28.5% (20/70) of patients had bilateral multifocal disease (more than one tumor location) that required bilateral cryo. Of those, 95% (19/20) were BDF. FOCAL CRYO SIDE EFFECTS (MORBIDITY) The hope for low morbidity associated with focal therapy has been confirmed by our results. All patients were continent (with no pads) immediately after the first procedure (100%). One recurrent patient converted to a second whole gland freeze, resulting in mild stress incontinence requiring pads while playing golf. Other authors confirm these continence results (11). As to potency, focal therapy did extremely well. 58/70 patients were potent preoperatively (pretreatment baseline function). 54/58 (94%) were potent postoperatively with or without the use of oral agents, to their satisfaction, within 6 months. However, 11 patients were ultimately rendered impotent by additional treatment (7 by additional cryo, 4 by a combination of ADT, radiation or radical prostatectomy). Interestingly, 4/12 preoperatively impotent patients were potent after the procedure. This was due to the immediate potency rehab protocol that we provide, if needed. 43/58 patients (74%) therefore ultimately retained potency. Again, these results are consistent with other focal therapy series. No other complications were noted. Blood loss was virtually zero. No rectal fistulas were seen and no patient needed a 6 Prostate Cancer Communication / Spring 2014 • www.paactusa.org further procedure for urinary obstruction. CONCLUSIONS The long term results of focal cryoablation, within the limitations of our data, is significantly superior to traditional RP and radiation. Unanticipated is that patients at high risk for recurrence have a much higher disease free survival than that reported with robotic RP and with better quality of life. Repeat treatment for localized recurrence does not appear to negatively impact patient disease specific or BDF survival, perhaps accounts for improved results in high and medium risk patients. Patients treated with bilateral multifocal disease appear to do as well as those with unilateral tumors. Most striking, all grades and PSA levels appear to have excellent results compared to other therapies. When including all risk levels of disease and bilateral disease, the overwhelming majority of patients would be eligible for this approach when appropriately diagnosed, staged, and treated by an experienced cryosurgeon. The Male Lumpectomy achieves these results with minimal morbidity in terms of incontinence and potency. The safety and long term efficacy of focal cryoablation is now established, though this is not to say that further study is not needed. Enough evidence is available, however, that I would have no qualms about offering this option to qualified patients. Future investigators now have the data to have a comfort level to conduct comparative Level One evidence studies between focal therapy, robotic RP and the various forms of radiation. This data also sets the bar high for focal therapy. When developing this approach, we tried to optimize every step of the procedure to give us the theoretically best outcomes possible with our current knowledge. All of the important aspects of our methods for selecting and performing focal therapy are supported by Level One data as being the best way to carry out this mission (3D-PMB for diagnosis and staging, cryo for the ablation). Since we are dealing with peoples’ lives, anyone carrying out focal therapy should adhere to the principles we have outlined in selecting and performing the procedure. Based on my experience there will be a plethora of focal therapy methods being touted in the near future. It’s going to take other investigators another ten years to figure out if their method can produce the same results. As a patient, you will be challenged to sort out proven treatments with a published, peer-reviewed track record vs. “the latest” innovations without long-term results. We have been going down the same path with prostate cancer for so long. Despite the best efforts of urologic surgeons and radiation therapists to improve the results of their traditional treatments, little progress has been made in improving survival and lowering complications. Focal therapy gives us a new, exciting and hope-filled alternative road to take. It will be the responsibility of the medical community to thoroughly compare focal therapy as we have outlined it, honestly and fairly, with traditional therapies. If this is accomplished I am confident that we will have embarked on a new era in prostate cancer management. REFERENCES (1) Stoyanova T, Cooper A, Drake J et al. Prostate cancer originating in basal cells progresses to adenocarcinoma propagated by luminal-like cells. Proceedings of the National Academy of Sciences, published online Dec. 2013. at http:// www.pnas.org/content/early/2013/11/25/1320565110.full.pdf+html (2) Onik GM, Narayan P, Vaughn D, et al. Nerve sparing cryosurgery for the treatment of primary prostate cancer: a new approach to preserving potency. Urology. 2002 Jul;60(1):109-14. (3) Onik, G. Miessau M, Bostwick DG Three-dimensional prostate mapping biopsy has a potentially significant impact on prostate cancer management. J Clin Oncol. 2009 Sep 10;27(26):4321-6. 2009 Aug 3. (4)Delongchamps et al. Multiparametric MRI is helpful to predict tumor focality, stage, and size in patients diagnosed with unilateral low-risk prostate cancer. Prostate Cancer and Prostatic Diseases (2011) 14, i232–237. (5)Abd-Alazeez1 A, Kirkham HU, Ahmed M et al. Performance of multiparametric MRI in men at risk of prostate cancer before the first biopsy: a paired validating cohort study using template prostate mapping biopsies as the reference standard. Prostate Cancer and Prostatic Disease (2013), 1–7. (6)Singh PB, Anele C, Dalton E, et al. Prostate cancer tumour features on template prostate-mapping biopsies: Implications for focal therapy. Eur Urol. 2013 Oct 6. http://www.ncbi.nlm.nih.gov/pubmed/?term=singh+anel e+prostate (7) Donnelly BJ, Saliken JC, Brasher, PMA et al. A randomized trial of external beam radiotherapy versus cryoablation in patients with localized prostate cancer. Cancer 2010;116:323-330. (8) Ablin et al. Cryobiology, 8:271, 1971. (9) Waitzl R, Solomon S, Petre E et al. Potent Induction of Tumor Immunity by Combining Tumor Cryoablation with Anti–CTLA-4 Therapy. Cancer Res; 72(2) January 15, 2012. (10)Ginzburg S, Nevers T, Staff I et al. Prostate cancer biochemical recurrence rates after robotic-assisted laparoscopic radical prostatectomy. JSLS 2012;16:443-50. (11)Bahn E, Abreu AL, Gill I et al. Focal cryotherapy for clinically unilateral, lowintermediate risk prostate cancer in 73 men with a median follow-up of 3.7 years. Eur J Urol 2012 July;62(1)55-63. TREATMENT OPTIONS FOR POSTPROSTATECTOMY INCONTINENCE GARY E LEACH, MD • DIRECTOR - TOWER UROLOGY INSTITUTE FOR CONTINENCE TOWER UROLOGY - LOS ANGELES, CA Loss of bladder control (urinary incontinence) after prostate surgery is a devastating complication, which has significant negative impact on quality of life. The �good news’ is that with appropriate evaluation and treatment, the incontinence problem is usually treatable with significant improvement in quality of life. It is not unusual that lack of bladder control is a problem for the first few months following radical prostatectomy. A biofeedback program may be helpful during this time period to help restore bladder control. When urinary incontinence persists for more than 3-6 months after radical prostatectomy, appropriate bladder testing (called urodynamics) is critical to evaluate the function of the bladder and sphincter (valve) muscle to determine the exact cause of the postprostatectomy incontinence (ppi). This urodynamic testing is performed in the office and takes about 20 minutes. The test involves filling the bladder through a special catheter inserted in the penis, while measuring the pressures in the bladder. During the test, various maneuvers are performed to evaluate the bladder function, demonstrate the urinary incontinence and thus, specifically, define the cause of the urine loss. Normally, as the bladder fills to capacity, there is very little change in bladder pressure and the sphincter remains closed allowing the man to stay dry. When incontinence occurs following prostatectomy, this normal balance of bladder and sphincter function is disturbed. Our research has defined three main causes of ppi based upon urodynamic findings: 1. High pressure (with �spasms’ of the bladder) developing in the bladder as the bladder fills (50% of men with ppi). It is possible that these bladder spasms are related to nerve damage that may have occurred as a result of the prostatectomy. These bladder spasms may cause urge incontinence (the need to rush to get to the bathroom), frequent urination and sometimes loss of urine at night. This high pressure bladder dysfunction can also occur following pelvic radiation therapy. Normally, when the bladder fills, the bladder pressure remains low without any spasms. 2. Damage to the sphincter muscle (35% of men with ppi). This damage results in stress incontinence with loss of urine during change in position, coughing, straining or vigorous physical activity. www.paactusa.org • Spring 2014 / Prostate Cancer Communication 7 3. A combination of bladder spams and sphincter damage (10% of men with ppi). Men with this combined problem usually experience “mixed incontinence” symptoms with a combination of both urge and stress incontinence. TREATMENT OPTIONS Biofeedback/Pelvic Floor Training may be a treatment choice in men who are incontinent and desire treatment early after radical prostatectomy (especially within the first 3-6 months following surgery). Biofeedback is also a useful treatment option in men who have more minor degrees of incontinence. The treatment program involves weekly visits for one hour per visit with a trained therapist. A special sensor is inserted into the rectum and attached to the biofeedback computer. During the treatment session, the patient is taught to contract and strengthen the pelvic muscles with this muscular contraction being displayed on the computer screen. Also, an electrical signal can be sent to these pelvic muscles to help strengthen the muscles. Each week, the goal is to make the muscles stronger. Many men experience significant improvement in bladder control with this biofeedback program. When the main cause of the incontinence is high bladder pressures, medications to relax the bladder are usually effective. These medicines work by blocking nerve receptors in the bladder. Blocking these receptors results in decreased bladder contractility and improvement in bladder spasms. Medicines to relax the bladder (generally known as anticholinergics) include: Enablex, Vesicare, Ditropan XL, Detrol LA, the oxytrol patch, oxybutynin 3% gel and imipramine. Side effects of these medications may include dry mouth, constipation, and blurry vision. These drugs should not be used in patients with uncontrolled narrow angle glaucoma or in men who do not empty their bladder well. There is also a new type of oral medication, called Myrbetriq, which helps relax the bladder by stimulating different receptors in the bladder wall. Thus, Myrbetriq does not cause the typical dry mouth and constipation side effects so common with all the other medications that have been used for years. However, 10% of those who take Mybetriq may experience some increase in blood pressure. Many men that have not been able to tolerate the traditional medications used in the past, benefit from this new medication. When the oral medications fail to control the high bladder pressures, the Interstim “bladder pacemaker” device can be an excellent treatment option. This bladder pacemaker device can be tested in the office with promptly 70% of the patient’s responding during the seven-day test. If there is a beneficial response to the seven-day test, implantation of the permanent bladder pacemaker can be considered. This procedure is performed as an outpatient under local anesthesia. Another option for controlling high bladder pressures, when the 8 Prostate Cancer Communication / Spring 2014 • www.paactusa.org oral medications are not successful, is Botox injection into the bladder. The Botox is injected in the office setting through the cystoscope with approximately a 50% success rate. The Botox usually has a maximum duration of benefit in the range of six months requiring repeat injection on a regular basis. There is also a 5% risk of urinary retention associated with Botox injection. If urinary retention should occur, the patient may be required to perform self-catheterization 3 to 4 times per day until the effect of the Botox diminishes. Both the Interstim bladder pacemaker device and Botox injection are now covered by Medicare. Options for treatment of sphincter damage include biofeedback, injection therapy (which is generally not successful), the artificial urinary sphincter, and the male sling procedure. Those men with “mixed” bladder and sphincter malfunction undergo initial treatment (usually with anticholinergic drugs, Interstim or Botox) to improve their bladder function (i.e. lower their bladder pressures) followed by treatment to address the weak sphincter (if necessary). Commonly, follow-up urodynamic studies are performed to evaluate the response to each stage of therapy. INTERSTIM “BLADDER PACEMAKER” When the usual medical treatments to lower high bladder pressures are not successful, the Interstim “bladder pacemaker” may be an excellent alternative. This treatment involves an office test with placement of wires next to the nerves that control the bladder under local anesthesia. For seven days, the patient wears a battery in the belt which sends an electrical signal to the nerves that control the bladder. The goal of this stimulation is to relax the bladder during filling. This office test of the Interstim device is approximately 70% successful. If the patient responds well to the office test, the permanent Interstim device is implanted as an outpatient in the hospital under local anesthesia. This procedure involves placing a special stimulation electrode in the lower back next to the main nerve that controls the bladder (Figure 1a). This stimulation electrode is placed through a special needle under local anesthesia without the need for a large incision. Next, the implantation of an internal �pacemaker’ generator that is attached to the stimulation electrode is performed and then programmed through the skin (Figure 1b). The generator is very similar to a heart pacemaker with a battery that usually lasts 8-10 years. Overall approximately 70% of patients respond to the office trial of test stimulation. When we proceed with the permanent implant, approximately 85% of patients have an excellent response. Use of the Interstim “bladder pacemaker” is an effective, relatively “non-invasive” treatment option for those patients who have high-pressure bladder dysfunction who do not respond to the usual forms of medical treatment. Surgical treatments for stress incontinence due to sphincter damage following prostatectomy include the Artificial Urinary Sphincter (AUS) and the Male Sling Procedure. In general, injection therapy (i.e. collagen, Durasphere, etc.) has not been successful in men with sphincter weakness. This lack of success is due to the migration of the injected material away from the sphincter area after injection. Figure 1a: Interstim stimulation electrode placed next to nerve that controls the bladder. Figure 1b: Internal Interstim generator attached to stimulation electrode. THE ARTIFICIAL URINARY SPHINCTER (AUS) Perfected over the last 30 years, the artificial urinary sphincter is a device implanted into the body to correct stress incontinence in men with significant sphincter damage. The AUS has three components: a cuff that helps close the urethra, a pump placed inside the scrotum, and a pressure regulating balloon which is placed in the lower abdomen (see Figure 2). When the man wants to urinate, he squeezes the pump in the scrotum, which opens the cuff around the urethra. Automatically, after 3-5 minutes, the fluid returns into the cuff allowing the cuff to close. After the device is tested during surgery, the cuff is “locked” open, and is only activated when swelling around the pump is gone (usually about 4-6 weeks after surgery). With the current model of the AUS, long-term patient satisfaction has been excellent with less than a 15% mechanical malfunction rate at 10 years after implantation of the device. Despite these excellent long-term results, however, some men are hesitant to have this prosthetic device placed. For these men, as well as for those with more minor degrees of ppi (or for men who do not have the manual dexterity to squeeze the pump in the scrotum), the male sling is a promising alternative. Figure 2: Artificial Urinary Sphincter in place. MALE SLING PROCEDURE Over the last few years, the male sling procedure has become a viable treatment alternative for men with ppi due to sphincter damage causing stress incontinence. The “best” candidates for the male sling are men with more minor degrees of stress incontinence (< 2 pads/day), men with no previous history of pelvic radiation therapy and men who have not had a previous AUS inserted. The surgical procedure to implant the sling takes about one hour and can be done either on an outpatient basis or with an over-night hospital stay. The purpose of the “sling” is to compress the urethra and help eliminate loss of urine with coughing, sneezing or vigorous activity. The sling is placed via an incision between the scrotum and rectum (see figure 3). In the author’s experience, the most effective material used for the sling is a specially prepared synthetic patch which compresses the urethra. A catheter is usually left in place for 24 hours with most men being able to urinate with good control immediately after the catheter is removed. Figure 3: Male sling secured into position. Thus far, the results with the male sling in properly selected patients have been encouraging. Approximately 30% of men are completely dry, 40% are significantly improved, and 30% are considered failures. If the male sling is not effective, an artificial urinary sphincter may be considered as a second alternative. SUMMARY Recent advances in the evaluation and treatment of men with incontinence following prostate surgery have allowed many men to regain their urinary control and improve their quality of life. Men with significant incontinence following treatment for prostate cancer should have an appropriate evaluation (i.e. urodynamic testing) to determine the exact cause of their incontinence. Appropriate treatment based upon the results of this testing usually results in significant restoration of bladder control and improvement in quality of life. HOW TO OBTAIN MORE INFORMATION: Additional information can be obtained on the Tower website: towerincontinence.com or towerurology.com Also, Dr. Leach can be reached by e-mail: DrDorado@aol.com. References: 1. G Leach, B Trockman, and A Wong, et al.: Post-prostatectomy incontinence: urodynamic findings and treatment outcomes. J. Urology 155:1256,1996. 2. F Haab, B Trockman, P Zimmern, and G Leach: Quality of life and continence assessment of the artificial urinary sphincter in men with minimum 3.5 years of follow-up. J. Urology 158:435-439,1997. www.paactusa.org • Spring 2014 / Prostate Cancer Communication 9 WHAT THE HECK HAS BEEN GOING ON IN MY WORLD- PART 64! B Y M A R K A . M O YA D , M D , M P H , U N I V E R S I T Y O F M I C H I G A N Note: A total of 64 times in a row (and for 15+ years!) I have written and volunteered for this newsletter, and I have yet to receive any personal financial compensation or personalized classic timeless gifts such as: a device that immediately turns OFF the show “Duck Dynasty” when it comes on the television set (I don’t get it…crazy Grandpa says something crazy and people lose their mind like they expected him to be able to split the atom one day or cure cancer or solve the world peace issue just because he can produce a great duck calling device), an official PAACT snow shovel, an official PAACT space heater and blanket, official PAACT salt pellets for the icy driveway, a first class ticket to Kona, Hawaii BECAUSE I CAN’T TAKE THIS SNOW AND COLD ANYMORE, and in fact ”I am mad as hell and I am not going to take this anymore!” (From the Movie “Network” Circa 1976 - it won 4 academy awards). PS. If Bing Crosby would have recorded a follow-up song to White Christmas called “I am dreaming of a Green Dry Spring” he would have made billions of dollars this year (well - actually his estate would have made billions, but you get my point)! PPS. Oh and to my parents who are living in Florida right now…I get it! No more! You don’t need to call me 24 hours a day, 7 days a week and instead of saying “hello” on my message machine you start every message with “it was 80 degrees today!” and then you get to the “we love you” part. If you loved me you would cease and desist telling me about the weather in your part of the world or acting like you are working for the weather channel in Sarasota, Florida. I am your fragile son and without any ultraviolet light the next best thing is to NOT remind me of the importance of regular ultraviolet light…oh and I love you too mom and dad #needsnowgoneasap. PSEUDO BREAKING NEWS (note: this is not really breaking news but I thought it would get your attention - hey network news stations do this all the time and announce “breaking news” and in reality it is just Miley Cyrus stubbing her toe or something like that)… I am asked about fruit juice all the time, so let me put it to rest (but the next story on vitamin E is really breaking news!). 270) Fruit juice and many exotic and pricey juices are the new Coca-Cola or Pepsi in the Moyad World? (Reference: Coca-Cola Web Site and Fruit Juice Web Sites) BOTTOM LINE I received many questions on this and let me try and give my quick and simple opinion - I believe most fruit juices are simply the same as drinking a sugary cola or worse. For example, 1 can of Coca Cola contains 140 calories and 39 grams of sugar, and 12 ounces (1 can) of apple juice has 180 calories and 42 grams of sugar!!!! WOW!!!! In other words, in many situations I think fruit juice is the same or worse than sugary soda! 10 Prostate Cancer Communication / Spring 2014 • www.paactusa.org WHAT ELSE DO I NEED TO KNOW? Nothing else! Just in case you missed it lets review: COCA-COLA 8 OUNCES = 26 GRAMS OF SUGAR AND 95 CALORIES APPLE JUICE 8 OUNCES = 28 GRAMS OF SUGAR AND 120 CALORIES! GRAPE JUICE 8 OUNCES = 36 GRAMS OF SUGAR AND 140 CALORIES ORANGE JUICE 8 OUNCES = 22 GRAMS OF SUGAR AND 110 CALORIES POMEGRANATE JUICE = 31 GRAMS OF SUGAR AND 150 CALORIES ANY QUESTIONS? Yikes!!! Oh, but Dr. Moyad those fruit juices have some vitamins and minerals in them so that is good, right? Look, I had a large pepperoni pizza with a lot of cheese last night and beer and that had vitamins and minerals in it too! The calorie and sugar counts on these juices simply outweigh any benefits, so personally I stay about as far away from them as an Ohio State Football Class Reunion party (I am talking about the Coach Cooper years when we used to beat Ohio State all the time)! REAL BREAKING NEWS 271) Vitamin E supplements at 2000 IU per day might slow functional decline in patients with Alzheimer disease and reduce caregiver time by up to 2 hours per day! And, it was about as safe as a placebo. So, why the heck are you mentioning this in the PAACT newsletter for prostate cancer when we already know this supplement can increase the risk of prostate cancer?! Moyad is losing it folks! (Reference: Dysken MW et al. JAMA 2014;311:33-44) BOTTOM LINE Vitamin E dietary supplements can slow functional decline in patients with mild to moderate Alzheimer disease. Dietary supplement recommendations should be individualized based on the disease and situation (like Rx drugs) and should not be generalized in terms of recommendations. WHAT ELSE DO I NEED TO KNOW? Vitamin E and memantine (Namenda®) have demonstrated some benefit in moderately severe Alzheimer disease (AD), but there is a lack of evidence in mild to moderate AD. Researchers initiated a major clinical trial to determine if vitamin E at 2000 IU/day, memantine, both, or placebo slows progression of mild to moderate AD in patients already utilizing an acetylcholinesterase inhibitor (AChEI or conventional treatment). This was a double-blind, placebocontrolled, parallel-group, randomized clinical trial with 613 patients with mild to moderate AD at 14 Veterans Affairs medical centers. there are exceptions such as Alzheimer disease. Yet, what if someone was diagnosed with prostate cancer and has Alzheimer disease. This would be a decision that you and the doctor you trust the most must make, but it should be an option for any Alzheimer patient, so ask your doctor ASAP. After an average follow-up of 2.27 years, participants ingesting vitamin E had a delay in clinical progression of approximately 6.2 months. Caregiver time was reduced by 2 hours per day in the vitamin E group. Safety and all-cause mortality were not different among groups overall. Thus, patients with mild to moderate AD utilizing 2000 IU of vitamin E per day compared to placebo resulted in reduced functional decline and caregiver burden and it was overall very safe. It did not delay cognitive or memory deterioration but it did temporarily protect their ability to perform daily activities like feeding themselves and putting on clothes. This is a big deal folks, especially since it costs pennies a day. This clinical trial represents remarkably good news not only for Alzheimer patients, but the dietary supplement industry and I find it ironic that just 1 week before the publication of this groundbreaking article there were “experts” in multiple reputable journals arguing, without any rebuttal, that supplements, in general, are a waste of money. Well, let me give you some advice, similar to dealing with people, religion, race, ethnicity, political parties, medications etc., please do not generalize because it only makes one look naïve, and ill informed. Vitamin E has a critical role in a few areas of medicine, and just because it is not prostate friendly does not mean it should never be used! This is a classic point I try to teach students, consumers, and health care professionals every week and some get it and some do not, but hopefully after reading this part of the newsletter it will shed high beam lights on how to deal with any future pill that someone recommends or not. So, when you read an article that stating that fish oil might increase the risk of prostate cancer, this does not mean it is true, nor does it mean that that fish oil would have no place in medicine. Every supplement at a certain dosage is dangerous, and not needed by many, but at the same time it might be needed by other individuals. Look at aspirin, depending on your situation you might need a high daily dosage, moderate daily dosage or even a baby aspirin or you might need to stay away from it entirely because the risk of ulcers or internal bleeding exceeds the benefit. Geez, this was a really serious opening to my column! However, this was a serious topic that required little to no levity. Hmmmm…. “Supplements don’t work!?” “Don’t waste your money!” “Vitamin E increases the risk of prostate cancer so do not use it for any other medical condition.” These are just some of the ridiculous, silly, or inane generalizations or comments I hear from “experts” on a regular basis. I have tried for decades to convince the public and health care professionals that like prescription drugs dietary supplements can be immensely helpful, could have no impact, or be downright dangerous depending on the specific medical condition. We need to eliminate the perceived and realistic bias by some in the medical profession that appear to just want to answer the supplements question with a generalized and sweeping “yes” they work or “no” they don’t work. Supplements are really no different than over the counter or prescription drugs that need to be individualized. Generalization in the supplement world, like in life, is a mistake you should never make especially after this clinical trial (the equivalent of a phase 3 by the way, an incredibly well done trial - actually outstanding). If this supplement were a drug it would have a shot at FDA approval after these results. Vitamin E supplements significantly slowed functional decline by 6 months (similar to FDA approved drugs) and reduced caregiver time by approximately 2 hours per day, which could be the difference between patient independence and dependence! These are, I believe, striking results for a dietary supplement that only costs pennies a day! In other words, vitamin E now arguably becomes a potential major player for the treatment of individuals with Alzheimer disease if this is true, because let’s face the facts here, there are no great treatments for Alzheimer disease! Yet, it does not change the fact that it should not be used, for the most part, in those concerned about prostate cancer. In other words, the risk exceeds the benefit for most individuals, but 272) Mercury dental fillings and fish with some mercury are bad for you and can encourage many diseases?! Hmm and did I tell you that Big Foot and I were best friends in high school and UFOs land in my backyard every Saturday afternoon in Fall so the Aliens can walk to the Michigan Football games from my house without paying the high price for parking?! (Reference: Nicolae A, et al. BMC Oral Health 2013;13:44) BOTTOM LINE The benefits of eating fish outweigh the negatives and the benefits of mercury fillings outweigh negatives. WHAT ELSE DO I NEED TO KNOW? I am concerned, in rare cases, about over exposure to mercury but the problem is the lack of objective reporting by some “experts.” For example, in one of the largest studies ever conducted on mercury exposure from fish (Mozaffarian www.paactusa.org • Spring 2014 / Prostate Cancer Communication 11 D, et al. N Engl J Med 2011;364:1116-1125) that included over 170,000 men and women, researchers found a LOWER risk of cardiovascular disease in those with higher mercury exposure. In other words, overall, the benefits of eating fish outweighed the negatives (the higher exposure to mercury). However, I believe there are some cardiovascular concerns with higher mercury exposure but overall fish with higher concentrations of omega-3 fatty acids (anchovies, herring, mackerel, salmon, sardines, trout, GREAT LAKES WHITEFISH…) tend to be less concerning. One of the better studies ever conducted on mercury in teeth was completed recently in Canada and found that dental amalgams were NOT a hazardous source of mercury in humans. These researchers looked at the average mercury concentration in the population and the number of amalgam surfaces. Overall, mercury levels were well below those associated with health risks. Still, this study just adds to the majority of studies conducted in the U.S. and Europe that have NOT FOUND any issues with dental amalgam. Mercury levels considered to be safe in the urine (if you are really curious) are 5 ug Hg/g Cr (expressed as ug Hg per gram creatinine) or 7 ug Hg/L (expressed ug Hg per liter of urine). Keep in mindjust because a blood test or urine test shows you have higher mercury levels should not discourage you and should not make you want to take out mercury fillings. I have several mercury fillings and I have never had a mercury urine test because I have never been concerned about it and I would rather spend my time wondering why people stick up their middle finger at me and yell when I drive the speed limit. DMSA (dimercaptosuccinic acid) has been used to reduce lead intoxication when specific criteria are met (check with your doctor) and it has been used in some rare cases for other metal exposures such as mercury. I have received many letters about getting DMSA from an alternative medical practitioner, if you have cancer, to reduce toxins and slow the growth of the cancer. I don’t think this is a good idea. DMSA works by binding to these metals and forming a metal complex, which is then excreted in the urine. However, DMSA is also controversial because it may be over hyped and used to promote large benefits in a variety of situations like those with Autism Spectrum Disorders and cancer. It has a purpose for those over exposed to lead but otherwise should not be given carelessly. Part of what DMSA is touted to do is potentially raise glutathione levels (an antioxidant produced by the human body), but this can also be done through heart healthy lifestyle changes. 273) Almost everyone is actually deficient or does not get enough of a specific nutrient! No, it’s not just potassium as I mentioned in the last issue (FY I- recommended daily allowance, RDA, for potassium is 4700 mg per day, but 12 Prostate Cancer Communication / Spring 2014 • www.paactusa.org this mystery nutrient has an RDA of 420 mg per day or less!). So, what is this other nutrient? (Reference: Del Gobbo LC, et al. Am J Clin Nutr 2013;98:160-173.) BOTTOM LINE Magnesium, especially from food sources should be your new best friend! Remember in the last issue that potassium has simply become the forgotten nutrient in most individuals and in those taking Zytiga! The recommended daily allowance (RDA) is very high or 4700 mg per day. I have never met a single person that knows this! However, low magnesium levels are also a problem in many individuals including those taking acid reflux medications, metformin and probably many other drugs. WHAT ELSE DO I NEED TO KNOW? Low magnesium is a big, big problem for many men and women reading this column right now. Why? Few people realize that the recommended daily allowance (RDA) is less than 420 mg a day for almost everyone except it is hard to get this amount. How about taking a simple magnesium dietary supplement? Not a bad idea but if you take too much it can cause really soft stools (not the bean bag chair kind you have in your living room) and diarrhea. Still, most Americans are not getting enough potassium in their diets (mentioned in a previous Moyad column) nor are they getting enough magnesium. Dietary magnesium has been associated with a lower risk of cardiovascular disease (CVD) and may prevent a lot of health issues. Very low magnesium might increase the risk of cardiac problems including arrhythmias. Numerous popular drugs used by some prostate cancer patients can reduce blood magnesium levels including metformin and acid reflux drugs. Increasing levels of blood glucose and insulin can reduce magnesium as well as alcohol intake. There is now evidence that lower intakes of dietary magnesium are associated with a greater risk of CVD and dying from CVD. Magnesium also helps reduce the risk of constipation and kidney stones, which is why many calcium supplements now contain some magnesium. What is the impact of magnesium on prostate cancer? We have no idea, but the overall health benefits are so outstanding that everyone should know about this nutrient. The recommended dietary allowance (RDA) of magnesium is approximately 400420 mg per day for adult men and 310-320 mg per day for adult women. Green leafy veggies such as spinach and higher fiber foods tend to contain more magnesium. For example, nuts such as almonds, seeds, and beans (soybeans…) are good sources. One of my favorite sources is avocado because it is also high in potassium and healthy fat. Fish, brown rice, plain yogurt, and even bananas are also high in magnesium. You can take a magnesium supplement, but keep in mind that primarily heart healthy foods are a good source of magnesium, so it is best to stick with food sources. Magnesium is a forgotten nutrient today (kind of like the Rubik’s cube or pet rock of nutrients) because it is not expensive and does not grab major headlines, but it has quietly become a major player in improving health and wellness. Similar to the Michigan football team that deserved to beat Ohio State in football in 2013 (No, I will never live that game down), magnesium deserves more attention and respect! Regardless, I hope you get more magnesium in your diet in 2014 and if you are really curious ask your doctor to pull your magnesium blood level next time you give blood because it will give you a good idea of how you are doing (it is an accurate test folks)! There is preliminary research that magnesium in drinking water and other sources might reduce the risk of prostate cancer, but this is so preliminary that I would assume for now that magnesium has no impact on prostate cancer but does impact overall health. Again, review my favorite list of magnesium foods and see how heart healthy they are for you! Dr. Moyad’s 5 Favorite Magnesium Sources (apart from a banana): 1. Avocado = 50 mg per 1 cup (healthy fat, packed with potassium and magnesium and good with pretzels and beer) 2. Spinach = 80 mg per ½ cup boiled (Okay throw some butter in with it and who doesn’t love this stuff with beer and chips) 3. Plain Yogurt = 40 mg per 8 ounces (love this stuff with chips and beer) 4. Almonds = 80 mg per ounce (love Almonds with beer and chicken wings) 5. Oatmeal = 1 instant packet = 35 mg. Okay, I really can’t stand oatmeal because to me, it has no taste unless I dump a lot of brown sugar in it or drink beer afterward and have a pepperoni pizza. 274) Exercise may be working as well as some prescription drugs! And testosterone replacement therapy (TRT) might increase the risk of heart disease? What do these stories have in common Dr. Moyad, because you obviously put them together in the same article for a specific reason? Right? (Reference: Finkle WD, et al. PLoS One 2014;9:e85805. &Naci H, Ioannidis J. BMJ 2013;347:f5577). BOTTOM LINE “First do no harm” is my motto….oops that actually came from someone known as Hippocrates (bet he never was on the Dr. Oz show)! Right now, we have to assume testosterone replacement therapy (TRT) might increase the risk of cardiovascular disease (CVD) even though it has not been proven, because CVD is the number 1 cause of death in men. It’s possible that exercise is as good as taking a prescription drug in many cases and in the worst case scenario makes most prescription drugs work better, even testosterone replacement therapy (TRT), which is not a bad case scenario folks! WHAT ELSE DO I NEED TO KNOW? Testosterone replacement therapy (TRT) is an option some men choose after being treated for prostate cancer and have no detectable signs of disease for years and have very low testosterone (or if they simply watch enough TV and are convinced to use it from all those commercials)! It seems like from all those television advertisements, TRT makes your life so wonderful. I mean you are able to get the good looking girl, put her in your new expensive sports car and she laughs at all your jokes while the wind whips through her hair! What could be more wonderful than being a magnet to the ladies and taking TRT (okay - I realize this is silly but so are many of those commercials). What is the real problem here? Another new piece of research suggests that taking testosterone replacement therapy (TRT) might increase the risk of cardiovascular disease (CVD)/ heart attacks in men with heart disease. Many health care professionals and patients having been asking my opinion of this situation. I respond by saying “it doesn’t matter” or “it shouldn’t matter.” Folks look at me like I am 5 eggs short of a dozen, 2 beers short of a six pack, 1 quarter short of a dollar, the lights are on in my house but no one’s home or I am 2 gallons short of a full tank…MAN I COULD GIVE THESE DUMB ANALOGIES ALL DAY! What I mean is that since CVD is the number 1 killer of men, and over 800,000 men and women died from this disease in the past year, including 150,000 age 65 and younger, therefore, ALL MEN with or without diagnosed heart disease should be treated as if they are already at high risk of CVD. If you want to go on TRT, then all heart healthy numbers and lifestyle factors should be heart healthy. In other words, you should be losing weight/ waist, have a normal to low cholesterol, normal blood glucose, normal blood pressure and should be exercising daily and eating primarily a heart healthy diet (If you aren’t doing these heart healthy things, you SHOULD NOT be allowed to go on TRT). I watched for decades “experts” tell women that hormone replacement therapy (HRT) might reduce the risk of CVD and this turned out to be as wrong as the controllers of the Titanic thinking it could swerve around an iceberg! In a separate, but related article, one of the most extensive analysis ever conducted on the subject concluded that “exercise and many drug interventions are often potentially www.paactusa.org • Spring 2014 / Prostate Cancer Communication 13 similar in terms of their mortality benefits in the secondary prevention of coronary heart disease, rehabilitation after stroke, treatment of heart failure, and prevention of diabetes.” WOW! WOW spelled backwards! In a previous column in 2013 I mentioned that from Viagra to statin cholesterol lowering drugs to anti-depressants, it appears that if someone exercises regularly it makes their prescription drugs work remarkably better! TRT would also work better with exercise, and in some cases men would never need TRT if they lost weight/waist and their testosterone increased naturally and their risk of CVD also decreased. The take home Moyad message of the day is too many men (and women) have begun to rely on prescription drugs and supplements to solve many of the issues exercise and other lifestyle factors could solve. We already know exercise reduces the side effects of prostate cancer treatment, reduces fatigue (especially weight bearing exercise) and might even reduce the risk of prostate cancer recurrence. All of this new and old exercise research is nothing short of miraculous…kind of like when Michigan Basketball made it to the final four last year! However, they still should have beat Louisville but the referees cheated and called a foul at the end of the game on our best player who actually didn’t foul the Louisville player (Man - I need therapy). 275) What is the latest update with all this multivitamin research and cancer, heart disease, cataracts, Alzheimer disease, etc.??? (Reference: Grodstein F, et al. Ann Intern Med 2013;159:806-814, Gaziano JM, et al. JAMA 2012;308:1871-1880., Christen WG, et al. Ophthalmology 2014;121:525-534) BOTTOM LINE Should I still take a daily multivitamin? What do you take? Do you still take Centrum Silver or a Centrum Kids? What do you eat? Why did you wear that jacket? When are you going to cure prostate cancer? I get this question about a 1000 times a week and the answer is “yes” when it comes to the very first question about multivitamins, because it may reduce the risk of cancer and cataracts (the 2 big Cs)and it also might correct some minor nutrient deficiencies. Keep in mind that Centrum Silver® (or a children’s multivitamin) is one of the cheapest multivitamins in America and has the most evidence. Also, taking more than 1 pill a day is not needed. The research suggests that even if you eat really well including 7 servings or more of fruits and veggies, you might still benefit from taking a multivitamin daily! How groovy is that! WHAT ELSE DO I NEED TO KNOW? Why is the multivitamin the real piñata of the pill world right now? Bone headed “experts” are taking a whack at it daily! Come on and step right up-take your best shot! Wack! Wack! 14 Prostate Cancer Communication / Spring 2014 • www.paactusa.org One medical journal that I refuse to call out and identify (Annals of Internal Medicine) not only published the recent research that showed Centrum Silver does not impact cognition, but also in the same issue on Dec 23, 2013 allowed an editorial to be published without ANY rebuttal that was scathing and unusually candid about how multivitamins are simply worthless (“stop wasting money…”)! Wow! That really wasn’t nice (what a bunch of journalistic bullies)! However, let me put this into perspective for you without trying to be too dramatic; if you really thought taking a Centrum daily would impact cognitive function better than placebo within 10 years in incredibly healthy older doctors whose average BMI is 25, less than 4% are smokers, less than 9% are diabetics and most of whom are doing vigorous exercise weekly and eating 5 servings of fruits and veggies daily, then I have swamp land I want to sell you in Ann Arbor, Michigan where there is certain to be unlimited gold and oil embedded in it! It is absurd to think this pill could prevent Alzheimer’s and most other diseases in perfectly healthy individuals after just 11 years. However, what was truly surprising is that this is the same clinical trial that found a significant modest reduction in the risk of cancer in those with and without a personal history of cancer when taking this multivitamin compared to placebo, and this was one of the primary endpoints of the study. This is also the same study that found a modest reduction in the risk of the most common type of cataracts and cataract surgery when taking a multivitamin, and there is adequate research to suggest it could correct some minor nutritional deficiencies (vitamin D, B12, B6, etc…). This was also the study that showed it had no impact on heart disease but there were a small number of men that died from fatal heart attacks taking Centrum compared to placebo which was probably due to chance or luck or maybe not. Maybe Centrum has some heart healthy features! There has not been any other phase-3 like trials of multivitamins in the U.S. or really around the world! The folks jumping on the “let’s beat up the multivitamin bandwagon” are really acting silly. Patients and other health care professionals do not need physicians/researchers to act like Democrats and Republicans fighting on 2 different television channels but rather they need objectivity and education on what to do with all this mess! The multivitamin chaos was not just created by some members of the supplement industry, but also by some members of my own profession. Ask yourself these questions: Are you willing to pay pennies a day to slightly and potentially reduce your risk of cancer (even if you have been treated already) and cataracts (the number 1 cause of blindness in the world and one of the most costly annual Medicare procedures) with a pill that has the same side effects as a placebo that does not show any evidence to prevent other diseases right now? If the answer is “yes” then great and if the answer is “no” then that is okay too! My answer is “yes” and will stay “yes” until someone shows me that the risk exceeds the benefit. The other reason a multivitamin is interesting is because it is common now to find out that many medications and even alcohol reduces the amount of nutrients in the body. I was also expecting to see, in this large multivitamin study, that men eating a TON OF FRUITS AND VEGGIES per day did not appear to benefit from taking a cheap old Centrum Silver, but it appears they did just as much if not more than other men! Hmmmmmmm! Got to go now and take my Centrum Silver with my dinner! 276) Artificial sweeteners are bad for me and my cancer? Really, and if you believe that I have the next tour leaving in an hour to show you the Loch Ness Monster because he is in my basement sink swimming around and reading the newspaper. (Reference: www.efsa.europe.eu/en/topics/topic/aspartame.htm) BOTTOM LINE Please do not worry about artificial sweeteners! Just be happy! If the research changes I will let you know but for now the EFSA did a really good review. WHAT ELSE DO I NEED TO KNOW? On December 10, 2013 my prediction came true (No, not the one about Justin Bieber getting in trouble or the Roughriders winning the Grey Cup or the Seahawks de-Broncoing the Broncos because that had not happened yet)! Except no one cared because there was weak media coverage and this was not a controversial finding. The EFSA (European Food Safety Authority based in Parma, Italy) announced their investigation of aspartame (the artificial sweetener) and found that it was SAFE for human consumption. “This opinion represents one of the most comprehensive risk assessments of aspartame ever undertaken” said the Chair of the EFSA’s Panel Dr. Alicia Mortensen. A can of diet soda contains 180 mg of aspartame, which means an adult weighing 75 kilograms would need to drink more than 16 cans per day to exceed the EU acceptable daily intake level (EU level is 40 mg per kg of body weight and the U.S. level is 50 mg/kg). Sorry, I realize artificial sweeteners are really an easy target but in reality they are not absorbed by the body and really do not change blood sugar or insulin levels and in the case of aspartame it just consists of 2 little amino acids! So, enjoy your artificial sweeteners because I am getting my daily intake of them right now! Yummy! I am not worried about any artificial sweeteners but my favorite one in terms of taste and research is Stevia! Yummy! There are also a few new ones out there that I will keep you up-to-date on! Of course those with the rare medical condition like PKU have to avoid certain amino acids (phenylalanine) and sweeteners like aspartame. Otherwise it’s all pretty groovy folks! On the other hand, if you think you can drink 7 diet sodas a day and feel fine, you won’t and this is not due to the artificial sweeteners but is due to the lifestyle that encourages this kind of soda consumption. Someone that drinks too much soda also tends to have other unhealthy behaviors going on and a lack of good nutrition. So, basically you will feel about as good as the Mayor of Toronto after the police discovered the secret videotape but I digress (Man, those jokes never get old)! 277) Whey Protein Isolate (WPI) or another protein powder and when and why take it? What about chocolate milk? (Reference: Beasley JM, et al. Nutr Clin Pract 2013;28:684-690) BOTTOM LINE Sarcopenia is reaching epidemic proportions even in men with prostate cancer in my not so humble opinion. Whey protein isolate (WPI) and other powders are the most concentrated protein sources available commercially with little to NO SUGAR and can help with weight loss, and muscle development. Look for a protein powder with no sugar and over 20 grams of protein for about 100-125 calories. Chocolate milk is awesome, but if you are watching your waist then all that sugar and calories is a problem. WHAT ELSE DO I NEED TO KNOW? Exercising before protein powder intake allows for greater use of amino acids for muscle protein synthesis in both young and elderly men. Aging is associated with an ongoing reduction in skeletal muscle mass that is also known as “sarcopenia” (literally means “lack of flesh”). One theory as to why this occurs is that aging is associated with a greater protein breakdown compared with production, which is not observed in young adults. Men on hormone therapy for prostate cancer have a huge problem with sarcopenia because testosterone is needed to help combat muscle loss. Remember (let’s review a past study I focused on a while ago), in a wonderful recent study, a total of 24 elderly individuals (average age of 74 years) were body-matched to 24 young controls (average age of 21 years). Subjects were randomly assigned to the rest or exercise experiment, which included consuming 20 grams (normal meal protein intake) of a labeled protein at rest or after a single exercise task. The exercise consisted of 30 minutes of moderate intensity activity that included a combination of low-intensity cycling and weight lifting. Muscle protein fractional synthetic rates (FSRs) were also calculated, which can tell researchers if protein is being used to potentially make some muscle. www.paactusa.org • Spring 2014 / Prostate Cancer Communication 15 No differences occurred between protein utilization rates between young and old regardless of rest or exercise. The digestion and absorption kinetics are not different from a young and older male AFTER consuming dietary protein, especially right after exercise. Individuals should exercise and then ideally consume some protein AFTER exercising to permit a greater utilization of amino acids for muscle protein synthesis. Additionally, getting some concentrated protein after a workout can also suppress your appetite and help further with weight loss. Sarcopenia is a four-letter word in my vocabulary! And, the only thing ever discovered by research to prevent sarcopenia is weight lifting or some type of regular resistance exercise, which can stimulate muscle tissue (we live in a use it or lose it world). However, research has been accumulating over the past several years that dietary or supplemental diverse amino acid or protein ingestion may assist in preventing sarcopenia when used with resistance activity or weight lifting. Although, the ability to utilize amino acids in the muscle tissue appears to become less efficient with aging in women and men (why does everything get reduced or smaller with age except the prostate?). Perhaps there is a way to trick the aging process and ingest a moderate amount of protein right after exercise, when tissue rebuilding and repair takes place. This is what is suggested from this well-done study. And, I have to admit that I am not waiting on a 10-year randomized trial, but have already begun to incorporate this simple piece of advice for myself, and all of the individuals that seek my advice. I just finished a long work out and really wanted to have a Kit Kat bar but instead had a strawberry whey protein isolate drink that consisted of 125 calories and 25 grams of pure protein with no sugar or fat and little sodium and I have to admit it was really good. Using a high protein meal such as meat, fish, beans, or just using whey or another low-calorie protein powder (your choice) seems to give equivalent results to what was found in the previous study I mentioned, if consumed within about 30 minutes after your workout. There is some recent hype from a small study of bicyclists in the laboratory that suggests that chocolate milk is the best thing to drink after a workout. This is interesting and it is a choice but I do not think it is better than getting a whey, or soy protein 8 ounce drink in water. For example, chocolate milk can contain 200 calories or more while whey or soy is about 100 calories. And, chocolate milk has less than 10 grams of protein while whey/soy contains around 20-25 grams of protein! Chocolate milk has about 30 grams of carbohydrate and a lot of SUGAR (27 grams in one serving in many cases - as much as Coca Cola or even more) and whey and soy have little to no carbohydrates and fat and a little bit of sodium and again works as an appetite suppressant. What about protein bars? The only thing you should get from a 16 Prostate Cancer Communication / Spring 2014 • www.paactusa.org bar is a beer or fiber because most commercial bars have a lot of protein but also a lot of SUGAR and calories (200-350 calories). So, I do not recommend most protein bars. Many of us are working out to lose weight so picking a low calorie and high protein powdered drink after exercise makes more sense for many reasons. Next time you see me, I hope my enhanced sized biceps and triceps do not scare you! Bring on Mike Tyson (because I can run faster than him)! 278) LATEST NEWS FROM ASCO GU MEETING? (Reference: American Society of Clinical Oncology Web Site) BOTTOM LINE There were some groovy research presentations at the Annual ASCO GenitoUrinary Meeting in San Francisco, CA this year. Here are some of the conclusions: -Swedish research (abstract number 4) concluded the following: “Addition of local radiotherapy to hormonal treatment in patients with non-metastatic advanced or high-risk prostate cancer more than halved the 10 and 15 year prostate cancer specific mortality and substantially decreased overall mortality.” In other words, getting radiation treatment in addition to hormone therapy provided a substantial benefit in not only reducing the risk of dying of prostate cancer but from dying earlier of all causes. -There were several papers suggesting testosterone replacement therapy (TRT) given to hypogonadal men or men with abnormally low testosterone did not appear to increase the risk of prostate cancer or of prostate cancer returning after treatment. This is good news especially for men with very low testosterone but this needs more studies and it does not resolve the heart disease issues mentioned earlier in this column. -Dr. Scholz and others from Marina del Rey, CA (abstract 247) had an excellent paper showing that many men, almost one in three, still respond well to Xtandi (enzalutamide) and 21% had stable disease after failing other drugs like abiraterone and chemotherapy. So, after failing other drugs if it is true that about half the men can expect something positive to happen with the drug Xtandi then this is great! However, it would also be interesting to know how many men no longer responding to Xtandi would then respond to abiraterone or chemotherapy (vice versa). -Research from Japan (abstract 87) showed that after 1 year on hormone therapy many men have large increases in deep/ visceral AND superficial/subcutaneous belly fat (32-35% increases) and increases in bad cholesterol, triglycerides, and blood sugar. This is not surprising or shocking in terms of cholesterol but what is surprising is that men gain a lot of fat quickly if they do NOT AGGRESSIVELY EXERCISE WHEN ON HORMONE THERAPY! In the Dr. Moyad world no one receives hormone therapy unless they agree to exercise daily and lift weights twice a week (as long as they get doctor clearance and do not have bone metastasis). -Abstract 43 was a great review of the cheap blood test C-reactive protein (CRP), which appears to have some ability to predict overall survival in men with metastatic prostate cancer from preliminary research (higher values are more concerning), but a large prospective study is needed and it is interesting work. WHAT ELSE DO I NEED TO KNOW? I have written too much for this issue and my fingers hurt. I need to take a 3-month break before writing again. However, I love you all like family and I will see you soon! THAT IS ALL FOLKS! See you this SUMMER, when I will write about many other serious issues and give timeless advice in the next newsletter, such as: why it is never smart to drink 2 gallons of water wearing really tight jeans on a 4-hour airplane flight with the airplane bathroom out of service or why it is not smart to live in Michigan in the winter (especially during 2014) and forget to buy 20 pairs of 10-inch thick thermal underwear! HAPPY SUMMER - SOON I HOPE! CHALLENGING PC TREATMENT BIASES – IS NOTHING SACRED? BOB LEIBOWITZ, MD (DR. BOB) • COMPASSIONATE ONCOLOGY MEDICAL GROUP LOS ANGELES, CA • WWW.COMPASSIONATEONCOLOGY.ORG Please note the following corrections to Dr. Bob’s Dec 2013 article (Volume 29, Number 4) “Dr. Bob’s Treatments and Insights Regarding Prostate Cancer”: Begins the middle of 3rd Paragraph of article (Left most column page 3) should be replaced with: Far too often, I consulted on prostate cancer patients who had a radical prostatectomy initially, but a few years later when their PSA’s rose, they were then often treated with radiation therapy; and when their PSA’s again rose, they were finally treated with hormone blockade. They were not cured with surgery and/or radiation therapy, but still had the side effects from “curative intent” local radical therapies. These side effects often included impotence, incontinence of urine, fecal soilage, urinary discomfort and many other problems. Rightmost Column page 5 – Item Number 6), should be replaced with: 6.  When prostate cancer patients are treated with intermittent androgen blockade (IAB), the time spent “on” hormone blockade is prolonged, while the time spent “off” hormone blockade shortens. This clearly demonstrates progression to CRPC. M ost prostate cancer (PC) patients have acquired quite a bit of knowledge regarding the “best” way to administer hormone blockade. The answer to this question is obvious… whether you choose continuous androgen blockade (CAB) or intermittent androgen blockade (IAB) is determined by whichever way you and/or your doctor decide is best. Other less opinionated patients might chain themselves to their internet portal device and try to quickly read a few million abstracts describing the benefits and risks in the Dr. Bob’s Acronyms: battle between CAB vs. PC..........Prostate Cancer IAB, as they struggle CAB........Continuous Androgen Blockade Androgen Blockade to educate themselves IAB.........Intermittent HB..........Hormone Blockade on this contentious but CRPC ......Castrate Resistant Prostate Cancer critically important issue. PSA........Prostate Specific Antigen T............Testosterone In the last issue of PAACT NCCN......National Comprehensive Cancer Network from Dec 2013 (vol 29 ASCO.......American Society of Clinical Oncology #4), I expressed my very IRB.........Institutional Review Board COMG......Compassionate Oncology Medical Group strong opinions regarding TRT.........Testosterone Replacement Therapy hormone blockade (HB). BAT.........Bipolar Androgen Therapy Deprivation Therapy The reader may recall that ADT........Androgen AAC.........Anti-Androgen Cocktail I feel certain that CAB is PAP........Prostatic Acid Phosphatase the least effective form of AUA........American Urological Association AS..........Active Surveillance HB; IAB is better, but every NCI ........National Cancer Institute study testing IAB clearly Tax.........Taxotere® 2 demonstrates that your mg/m ...Milligrams Per Meter Squared BSA........Body Surface Area time on HB lengthens, UCSF.......University of San Francisco while your time off HB CT...........Chemotherapy shortens. Each subsequent cycle, consisting of 2 phases - on-HB followed by off-HB, results in shorter durations off treatment, longer durations on HB, PSA nadir levels that get higher with each cycle of HB – by definition, this is the classic progression that results in castrate resistant prostate cancer (CRPC). As I noted, I feel strongly that the most effective form of HB is a third choice – to use a single cycle of Triple Hormone Blockade®/Leibowitz Protocol, then do everything possible to prevent or postpone having www.paactusa.org • Spring 2014 / Prostate Cancer Communication 17 to go back on HB. And if you are ever urged to start another cycle of HB, you should instead insist on being treated with my 3-Pronged treatment protocol. It is my opinion that this is clearly the most effective and best way to use HB and always remember my first rule: “Everyone is entitled to their own opinion. Their own WRONG opinion.” Corollary: “Especially me.” As I explained in the last issue of PAACT, in my very strong opinion, the longer you are on HB, the more your illness is evolving into CRPC. Each month on HB brings you 1 month closer to CRPC and a shortened survival. The definition of CRPC is a rising PSA while you are on HB. If your doctor can find effective treatments that can delay or better yet, prevent the need to go back on HB, then by definition, you will not evolve into CRPC, since a rising PSA with normal or elevated testosterone levels is not CRPC. Every month a prostate cancer patient survives with a normal or even better supraphysiologic level of testosterone (T), is one additional month of survival… as opposed to when he has a rising PSA on HB, which, in my opinion, will shorten his survival one month. Until the past several years, the near universal opinion of academic prostate cancer experts, along with almost the same percentage of clinicians (or at least that is what they wrote and said) was that IAB should be considered experimental and should not be used outside of an experimental (Institutional Review Board {IRB} approved) study. In the late 1990’s, I was honored to be an invited speaker and panel participant at the annual Massachusetts Prostate Cancer Symposium. Some of the other panelists included Dr. Marc Garnick, A professor at Harvard Medical School whose predominant interest is urologic oncology, with a specialization in clinical investigation related to prostate cancer. We both had spent time (he still does) at the Harvard Medical School affiliated Beth Israel Medical Center. Other panel members included a family practitioner; a patient care advocate who was a prostate cancer survivor; a well-known, highly regarded academic urologist; a few other members that I sincerely apologize to because I have forgotten their names. Most impressive to me, our panel was privileged to have Dr. Anthony V. D’Amico, MD PhD, participate. He is, without doubt, one of the absolutely most brilliant and nicest people I have ever been blessed to know. He very likely is among a handful of the “all-time best” radiation therapists in the world; he is affiliated with Dana Farber/Harvard Cancer Center as well as Brigham and Women’s Hospital (both Harvard affiliated and I had the privilege to spend 6 months of my fellowship at these institutions). Dr. D’Amico has been a major contributor in countless ways helping to better treatment and control cancer along the entire spectrum of malignant disorders. His research in PC therapy is one of his major areas of expertise, resulting in major advances in patient 18 Prostate Cancer Communication / Spring 2014 • www.paactusa.org care, as well as in the basic science of PC. One of his major PC contributions is known as the D’Amico classification scheme dividing new patients with prostate cancer into 3 separate, welldefined prognostic categories: Low Risk, Intermediate Risk, and High Risk. Yes!!! That D’Amico – impressive, huh? The final panelist, equally as impressive to me, was also our moderator, Dr. Philip W. Kantoff. Like many of the other panelists, he is a professor in the Department of Medicine of Harvard Medical School. He was also the Director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Center, and is one of the most respected and knowledgeable prostate cancer experts in the world. The Symposium started with each panelist delivering their prepared talks and slide presentations. Following this, Dr. Kantoff, as moderator, lead us to discuss a number of controversial issues based on an imaginary (or actual) prostate cancer patient from his clinic who required a treatment recommendation at various stages of his illness. My most vivid memory involved Dr. Kantoff asking us about the type and manner of HB that we recommend for our patients. 1)“Who would treat this patient with IAB? Who would advise CAB??” Never being shy, my hand did not even wait for the entire question to be asked or even for my brain to select an answer before it shot upward, almost pulling me off my chair. “IAB” my hand seemed to force my mouth to yell out. The rest of the panel absolutely and unanimously disagreed with my hand and my mouth. Next question: 1)“What type of patient on hormone blockade, in your practice, do you believe is a candidate to be treated with IAB?” That same hand acted without hesitation, and Dr. Kantoff allowed me (reluctantly?) to answer: “All of them!” Surprisingly, none of the panelists shared this belief and once again they unanimously chose the exact opposite answer. 2) “Does anyone have any patient in their practice on IAB?” Hand – yes Everyone else – no!!! And finally, 3)“Does anyone believe that at any future time they will ever use IAB in their practice?” Only my hand rose. The unanimous opposition party that comprised all of the panelists, except Dr. Bob, only raised their hands when the offered choice was “No”; they cannot conceive of a time when they would ever treat any patient in their practices with IAB, instead they confirmed that they would always advise their patients to use CAB, and never to use IAB. About 4-5 years ago, I was reading a medical journal that published the authoritative National Comprehensive Cancer Network (NCCN) treatment guidelines for various cancers and that issue addressed the use of hormone blockade (HB) for prostate cancer patients. One of the authors was Dr. Kantoff. In spite of any differences of opinion we have had, he and I both know that he is far more intelligent than I am; that he has devoted his life to determining and proving scientifically, exactly which treatments are most effective and/or least toxic for every stage of prostate cancer, as well as a large number of other types and stages of cancer. His efforts benefit prostate cancer (and other types of cancer) patients everywhere; he advances scientific knowledge benefitting society by following the scientific method; leaving nothing to chance; proving each and every step by creating treatment protocols, participating in them, supervising them, analyzing their results, and then presenting the results at conferences and/or publishing these results in peer reviewed journals, textbooks, symposiums, while always ensuring that the rights and privacy of every patient remain his primary concern. I am sure that I omitted countless other major contributions that were, are and will be made by Dr. Kantoff, but not intentionally (it is 2am). Back to the NCCN guidelines for using HB to treat prostate cancer that I believe appeared in an April edition; they gave the exact same recommendation that had been articulated by a panel at the ASCO Prostate Cancer meeting in February of that same year (and Dr. Kantoff had expressed that same opinion). “CAB should be considered the standard of practice for prostate cancer patients requiring HB. IAB should be considered experimental and should not be given outside the context of an IRB approved clinical trial.” Nothing (yet) had changed for more than 15 years. But about 3 months later, I was reading (I think) a newspaper-type journal, probably “Oncology Times,” and I noticed a picture of Dr. Kantoff along with an article about HB. The author quoted Dr. Kantoff and I paraphrase: “Intermittent Androgen Blockade is at least as effective as CAB; and probably better.” Shocked but ecstatic and so pleased, I immediately wrote a letter to Dr. Kantoff asking him to please let me know if the article was accurately quoting him regarding the type of HB he advises. He promptly wrote back to me saying that in general the article was accurate, although in a few uncommon HB settings, he might have some reservations about using IAB. Around 1995, I had written that I believed IAB would eventually be shown to be superior to CAB, and in either 2008 or 2009, I was advised by Dr. Kantoff and others that soon to be reported studies were able to conclude that IAB should no longer be considered investigational. Over the next few years, IAB was generally considered the “standard of practice” method to prescribe HB. In January 2014, at the ASCO prostate cancer conference in San Francisco, more than 90% of the audience of physicians agreed that IAB should be the preferred way to use HB, rather than CAB. Please remember that it takes an extraordinarily long time for doctors to change their treatment preferences/prejudices. Later in this paper, I will present case reports from our own practice that will provide some insight into my choice for the title of this article. I used this same title in 2003 at the annual Massachusetts Prostate Cancer Symposium. The Symposium was sponsored by Massachusetts General Hospital Cancer Center, Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center, Dana-Farber/Harvard Cancer Center, American Cancer Society, Tufts-New England Medical Center, Massachusetts Prostate Cancer Coalition, Massachusetts Department of Public Health, New England Coalition for Cancer Survivorship, American Foundation of Urologic Disease, and several more. There were two invited keynote speakers for this meeting: Dr. Philip Kantoff and myself (“Dr. Bob” Leibowitz.) This was the first national conference where I had the privilege to be a keynote speaker and I felt that this was the ideal format to present my interpretation and analysis of the medical literature regarding testosterone and its interactions in PC patients at different times in their evolution, from hormone sensitive disease to hormone refractory and maybe back towards hormone sensitive again. This evolution results in HB betraying you and becoming a Benedict Arnold as it switches from killing PC cells to helping PC cells, and to seemingly becoming invincible – fortunately enormous advances in understanding these changes continue to result in more FDA approved effective treatments to help men to defeat their own evil Benedict Arnolds. We cannot cure metastatic PC, but our increasingly realistic goal is to change it to a chronic disease (like high blood pressure or adult onset diabetes mellitus) that you can live with and die with, but not die from. At Compassionate Oncology Medical Group (COMG), we continue to make extraordinary, compelling and impressive progress, as we endeavor daily to make even more effective advances for each of our patients along this path. We design individualized treatments; we never use institutionalized, rigid, recipe-book-type (“cookie-cutter”) fixed protocol approaches that force the participating study doctors to become robotic, and not allowing carefully crafted and studied creative innovations. www.paactusa.org • Spring 2014 / Prostate Cancer Communication 19 The standard of practice protocols that are FDA approved only improve the median survival of PC patients by 2.5 months compared to placebo. The standards of practice that were used before the approval of Taxotere® in May, 2004 to treat PC patients had never been found to prolong survival in PC. Prior to May 2004, no treatment for PC ever prolonged survival. I began to exclusively use Taxotere® to treat all my PC patients who needed chemotherapy beginning in 1997, seven years before the FDA approved it for PC. Our use of Taxotere® as part of my 3-Pronged protocol and our own modifications to reduce side effects, while markedly improving its effectiveness, is a major reason that patients continue to travel literally thousands of miles to see us. Please see our map on our Compassionate Oncology website that identifies the various countries and states that are home to our patients. More than 75% of our patients are not living in Los Angeles. At the January 2014 ASCO prostate cancer conference in San Francisco, CA, there was a poster presentation by Dr. Samuel Denmeade, Professor of Urology and Pharmacology at Johns Hopkins. His paper reported on their ongoing study that investigates the effect of rapid cycles of very high levels of T followed by a cycle of HB with castrate levels of T. Their study tries to determine if PC growth might respond to their unique and previously untested theories. The poster describes their approach and results: Authors of numerous medical articles that were published in the 1940’s, 1950’s, 1960’s and literally through today, reported that testosterone in some patients and at some stages of PC stimulated cells to grow, while in other situations, testosterone inhibited the growth of PC cells; and in the lab, the effect of T on PC cells follows a bell shaped curve…low levels of T stimulate PC cells to grow while high levels of T inhibit the growth of PC cells and the higher the level of T, the greater inhibitory effects on PC cell growth. This effect follows the classic example of a bell shaped curve. The same effect is seen when breast cancer cells are exposed to varying concentrations of estrogen. Low levels of estrogen stimulate breast cancer cells to grow, but high levels inhibit the growth of breast cancer cells; the higher the level of estrogen, the greater the amount of inhibition. oMust be on continuous androgen deprivation therapy (ADT) for greater than or equal to 1 year. o Rising PSA o Less than or equal to 5 total bone metastases and less than or equal to 10 total lymph node or soft tissue metastases. oNo worrisome lesions (high risk), e.g., spinal cord compression, urinary tract obstruction oPrior second line hormone therapy and/or prior chemotherapy allowed o No pain To find the specific medical references that confirm these “claims of mine” and will convince my loudest and most skeptical critics, please read the articles that I have posted on our Compassionate Oncology website, including “High Dose Testosterone & Prostate Cancer: Wait until you read this update,” “High-dose Testosterone Replacement Therapy and Prostate Cancer,” “TRT Case Reports: High-Dose Testosterone Replacement Therapy (TRT) and Prostate Cancer (CaP),” and “Testosterone Replacement in Prostate Cancer Survivors with Hypogonadal Symptoms” (BJU article May 2010; coauthored with Dr. Tanya Dorff, et al.). Also, see “Hormone Blockade: Continuous, Intermittent or?” and for 3-Pronged Approach case studies, read “Compassionate Oncology’s Latest Three-Pronged Approach Patient Case Studies.” You can also find them in the various DVD lectures that I have given (available FREE (only pay S&H) by calling our office or ordering on our website): DVD #4 (high-dose TRT), DVD #5 (IAB and high dose TRT), DVD #6 (high dose TRT and 3-Pronged), DVD #7 (high-dose TRT) and AAC, DVD #8 (3-Pronged), and DVD #9 (high-dose TRT and 3-Pronged). Our latest DVD will be coming out very soon – you can call our office to preorder your copy today. 20 Prostate Cancer Communication / Spring 2014 • www.paactusa.org • Men with CRPC could respond to rapid cycling between polar extremes of supraphysiologic and castrate T levels [Bipolar Androgen Therapy (BAT)]. • Rapid cycling disrupts adaptive auto-regulation of AR. • They call this “The Love Study” • Eligibility criteria: Men were started on T injections to achieve supraphysiologic levels of T above 1500 ng/ml (“normal” is usually about 300-800 in many labs). A TRT Case Report from COMG: S. B. 12/95: 7/03: 52 years old; GS 3+3/6 at John Hopkins Hospital; PSA = 7.3 5 mos. 2-drug hormone blockade Then saw Dr. Bob and was treated with 9 mos. Triple Hormone Blockade®, followed by Proscar® alone (Finasteride Maintenance® Therapy) Started high dose TRT; later added in some AntiAngiogenic Cocktail (AAC) Date (month/year) 9/03 11/03 1/04 3/04 5/04 7/04 (thalidomide 50mg added) 9/04 11/04 1/05 T 1498 1545 1539 2062 1043 3678 1540 2674 1214 PSA 8.11 5.7 7.1 5.6 8.35 7.32 8.66 8.59 7 Date (month/year) 3/05 4/05 6/05 8/05 11/05 12/05 (Leukine® added) 1/06 2/06 (thalidomide stopped; Revlimid® 5mg/day started) 3/06 4/06 5/06 6/06 T 1286 2237 1232 2068 1427 1474 2212 PSA 7.12 6.4 7.57 9.19 9.01 11.1 11.5 3181 9.25 2791 2059 1599 1863 6.92 7.8 7.62 6.99 Eleven years after his diagnosis of PC, he never received local treatment. His treatment was one 14-month cycle of HB and 3 years of high-dose TRT, along with some AAC. He expired unexpectedly, apparently in his sleep, and was found by his sister when he failed to show up at a restaurant where they planned to meet. Excerpts from his autopsy report: “Mr. B--- was diagnosed with moderately differentiated adenocarcinoma of the prostate gland circa 1996 and he has been under treatment since that time. At autopsy, there is no evidence of recurrent or residual tumor. The prostate gland demonstrates only benign stromal and glandular hyperplasia with no evidence of malignant tumor.” “In this case, Mr. B--- had 90% and 85% luminal compromise of the right and left coronary artery systems, resulting in greatly reduced oxygenated blood flow to the heart muscle (myocardium), and this in concert with hypertension placed him at great risk for a sudden, irreversible, fatal cardiac arrhythmia or clinical heart attack.” “Forensic Elements and Consultations: … Medical records: Limited records, primarily medication lists and records from Dr. Leibowitz office are received, reviewed, and retained in the autopsy file.” I spoke to the pathologist before he started to do this patient’s autopsy. He understood that the reason we asked for an autopsy was to determine if there was any evidence of PC: 1) In this man’s prostate gland – he said that normally they would cut the prostate into 2 equal parts – like an opened oyster with a top and a bottom. Instead he cut the entire prostate gland into 1 mm slices. This is the same technique that is done with a radical prostatectomy specimen. The finding: no PC anywhere in the prostate. 2) All of the lymph nodes that drain the prostate were sliced like salami. The finding: no PC cells. 3) Knowing that PC spreads to bone preferentially and especially to the vertebra of the spine, he carefully sectioned each vertebral body longitudinally trying to identify anything that could be metastatic PC. The finding: absolutely no evidence of any PC cells anywhere in this patient’s body. The cause of death was severe advanced bilateral coronary artery disease with 90% obstruction of the right coronary artery and 85% obstruction of the left coronary artery. These narrowed coronary arteries caused either a sudden fatal rhythm disturbance of the heart (like ventricular fibrillation) or a clinical heart attack (myocardial infarction). This is a case of low-risk PC treated without any local therapy. The patient only received 14 months of HB and later the AntiAngiogenic Cocktail (AAC). The autopsy confirmed that he had a pathologic complete response to these medicines alone. Please note that I (Dr. Bob) have been using high-dose Testosterone Replacement Therapy (TRT) on select PC patients in our practice since the late 1990’s. I vividly recall my first PC patient starting on TRT; my target T range was only 100-200. Over the next 6 years or so, I slowly raised the target T level, while always requiring oral and written, informed consent detailing all risks/benefits and treatment options. We also ordered extremely frequent labs, as well as scans and office visits. When a patient was started on TRT, we initially required weekly labs, including PSA and T levels. If there were not any problems, we gradually lengthened the intervals between their blood tests, but even today, the least often that labs are checked is monthly. We were surprised to find that for most patients, PSA levels did not increase in spite of rising T levels. However, in patients who still had an intact prostate gland, their T levels began to rise after HB was stopped or if they were being treated with TRT, the T would always stimulate their normal prostate gland cells to make PSA. HB does not kill normal prostate cells. Everyone with a normal prostate gland will have their PSA’s increase, usually starting about 2-5 months after HB is stopped. The levels of PSA rise in what I describe as a “step and plateau” pattern. Can HB cure PC? It certainly did for this patient. Part three of this article will be printed in the Summer 2014 issue of the PAACT Newsletter. ®Triple Hormone Blockade, Triple Androgen Blockade and Finasteride Maintenance are the registered trademarks of Robert L. Leibowitz, M.D. www.paactusa.org • Spring 2014 / Prostate Cancer Communication 21 ACKNOWLEDGEMENTS OF CONTRIBUTIONS October 1, 2013 through December 31, 2013 (YOUR NAME WILL APPEAR BELOW IF WE DEPOSITED YOUR DONATION BETWEEN THE ABOVE DATES) Memorial Contributions In Loving Memory of Lloyd J Ney, Sr. Founder of PAACT, INC., Grand Rapids, MI In Loving Memory of Lloyd Allen Kosoff Dr. William Kadan Frank Sesno John B Cataldo In Loving Memory of N David Neimark Sheridan & Dana Neimark In Loving Memory of John Phillip Wonderly Anonymous In Loving Memory of Cliff Harvey John & Margaret Atkins John & Nancy Johnson In Loving Memory of my Brother, John S Swiatko Died from Prostate Cancer November 7, 2012 Bob Swiatko In Loving Memory of United Airline Flight 811 Capt. David Cronin In Loving Memory of Jacob Griffis Mary Lamielle In Loving Memory of Gary L Brooks Nancy Brooks _____________________ In Honor of our Anniversary 58 years together Mr. & Mrs. Richard A Christian 22 Prostate Cancer Communication / Spring 2014 • www.paactusa.org Contributions ($1,000 and Above) Anonymous Hallagan, Charles Julian Braun Charitable Trust King, William Mackey, Robert Contributions ($500 to $999) Albrecht, Ted BioDerm Davies, Ronald Dornbush, K Terry Gross, Edward Leibowitz, Dr. Bob Riederer, Richard Rizzi, Ben Schwab Charitable Fund Patron Membership ($100 to $499) Anonymous Berg, Henry Boundy, Bruce Brecht, Marshal Brown, David Brown, Lytle Bucy, M Peyton Clauser, Ray Cole, Galen Colwill, John Cooley, Jack Copeland, William Curry, Dudley Davis, Porter Dennison, Mark Derris, David Dilley, A Newton Dobosh, Jack Funicello, Jim Gazarian, Arnold Geissinger, Lloyd Giangreco, Tom Green, Ronald Greenway, Robert Hawvermale, Herbert Hayden, Jerry Hearn, Gregory A Hevel, Don Hogan, Brian P Holman, Josef Hudak, Col. Jane Jacobs, Jerome W Kimura, Kei Korek, Michael Kremer, Fontaine Kulkarni, Anant Lair, Richard Lawrence, Virgil Lee, Richard G Lipschutz, Howard Loomer, F.D. Loring, Keith W Manheim, Stewart Marsh, John S McCormick, Jim Means, Chad Novak, Vincent Nowlin, Jon Parker, Maclyn Pepe, Richard Petronko Ronald Purdy, Peter Ritchey, Frank Romak, L Earle Rosenberg, Alvan Rubin, Hal Ryan, Willliam Sandelin, Karl Scarborough, Clark Sellers, William Shaline, John Shimer, Allan Snow, James Sullivan, William Taylor, Keith True, Sr., David Trueblood, Harry Vanspronsen, Bob Weinstock, William Willson, Guy Wood, Raymond Zaboji, George Zayon, Seymour PAACT Membership ($50 to $99) Abbott, Steve Abramson, Harold Alcantaro, David Anderson, D.C. Anonymous Baxter, Gary Beacham, Jerry Blaser, Donald Busch, Michael Byers, Donald Chapman, Ray Cilke, Victor Clark, Edwin Colangelo, Thomas Collins, James Cotsifas, Chris DeShazo, James Deveny, Charles Dibenedevtto, Mario Diffenbach, Paul Donnellan, Lloyd Dorminey, James Duggan, Edmund Earl, Ross Eshaghoff, Ned Faisst, Ralph Fleming, Steven Ganas, Steven Goldberg, Irving Greiner, John Hagan, Lamont Haley, Forrest Hamilton, David Hankins, Ronald Hann, C Stephen Harris, John Harris, Stanley Harriston, George Held, Leonard Helmus, Neal Hennessey, Charles Higgins, Donald Hoffman, Val Hone, John Hoppe, Lee Howard, Robert Hoy, Thomas Hummel, Richard Jacobsen, Eudell Jennings, Chuck Jones, Rodney Kahn, Morley Katz, Harry Kearns, Don Kintner, George Kortebein, Stu Kosoff, Allen Krejci, Dr. John Kulak, Harold Kusnirik, Robert Labuzeta, James Largman, Ted LaRose, James Laumeister, Bruce Leach, Thomas Leone, Nick Lescoe, Proctor Lewis, Fred Mackey, Stanley McCalla, Don McCauley, Bernard McLoughlin, James Meetze, William Merrill, Richard Meyer, Kenneth Michau, Michael Middleton, Byron Mosier, William Murphy, Jim Natowitz, Allen O’Connor, Ward Paradise, V.A. Pekelney, Albert Perissi, John Pfizer Foundation Matching Gifts Pierson, Glen Posner, William Prager, James Provenzola, Frank Reed, Victor Robertson, John Robinson, Elliott Roepke, Ross Rubinstein, Jack Schaffer, Hal Schlaug, Robert Schlicksup, Edward Schluter, Fredric Schmitt, Richard Schubert, Norm Schwartz, John Secrist, C Robert Sedlacek, Emanuel Shaw, Dr. Roger Sher, Harold Shetler, William Shoemaker, Win Shollin, Thomas Singer, Arthur Smith, Marvin Spaw, Rose Springer, Richard Steinoff, William Stern, Henry Steward, Philip Suhr, James Szarko, Walter Taormina, Sam Theis, Douglas Thompson, Richard Thornton, Samuel Ungar, Ralph Vanecek, Michael Veale, Rev. Donald Verhage, Ernie Vinciguerra, Art Watterson, John Weir, Robert Williams, Orville Winer, Arthur Winkler, David Wittrock, Bill Wojnar, Edward Wong, Clifford Young, Joseph Zhang, Yi Miscellaneous Contributions (less than $50) Allshouse, Gary Andree, Robert Baker, John Berger, D Blundell, James Boyd, John Burkett, Charles Burrus, Gary Daniels, Susan Dardzinski, Donald Davey, John Dreier, John Dunn, Joseph Fegers, R.J. Filippello, Vincent Gartner, Allen Goodsearch Greene, Arthur Grill, Leopold Hastings, Jack Heinke, Wayne Hensler, John Hyman, Joel Jackewicz, William Jones, William Kelly, Charles Kennedy, James Korff, Marvin Kottich, Charles Lederle, Donald Litten, James Logrippo, Frank Lowe, Alan Mazurek, Robert McCarthy, Michael McDowell, H Clay Miller, John Mills, Norman Minowitz, Charles Montgomery, George Moore, George Naugle, Gerry Noteware, Gary Partridge, Charles Paul, Peter Piersiak, Robert Pittelli, Rudy Pomerantz, Carol Porter, William Ruble, Robert Siegel, Joe Sirowitz, Charlene Sizer, John Spina, Charles Stanley, Louis Surgent, Barbara Trombley, Joseph Trush, Edward Tubergen, Morrie Urquhart,Wiley Wagner, Albert Warren, Carl Weikart, Hubert West, Robert Whitney, Robert Zlotnik, Jan Contributions by State & Province Alabama0 Alaska0 Arizona8 Arkansas4 California55 Colorado7 Connecticut2 Delaware0 Florida35 Georgia4 Hawaii2 Idaho0 Illinois4 Indiana8 Iowa2 Kansas1 Kentucky1 Louisiana0 Maine3 Maryland8 Massachusetts4 Michigan30 Minnesota1 Mississippi0 Missouri3 Montana1 Nebraska1 Nevada5 New Hampshire 1 New Jersey 19 New Mexico 1 New York 27 N Carolina 2 N Dakota 0 Ohio4 Oklahaoma2 Oregon5 Pennsylvania2 Rhode Island 0 S Carolina 0 S Dakota 0 Tennessee3 Texas6 Utah0 Vermont3 Virginia5 Washington7 West Virginia 2 Wisconsin4 Wyoming1 Washington DC 1 Contributions Foreign Australia3 Bulgaria0 Canada2 Cayman Islands 0 China0 Denmark0 England0 France0 Germany0 Grand Cayman Islands 0 India0 Indonesia0 Isle of Man 0 Israel0 Luxembourg0 Mexico0 New Zealand 0 Portugal0 Saudi Arabia 0 Scotland0 Slovenia0 Rep of South Africa 0 United Kingdom 0 www.paactusa.org • Spring 2014 / Prostate Cancer Communication 23 ADDRESS SERVICE REQUESTED 1143 Parmelee NW Grand Rapids, MI 49504 Phone: (616) 453-1477 Fax: (616) 453-1846 paact@paactusa.org www.paactusa.org NONPROFIT ORG U.S. POSTAGE PAID GRAND RAPIDS, MI PERMIT NO. 875 Join Us on Facebook! PA A C T M E M B E R S H I P F O R M Name: Birthdate: / / Address: City: Telephone HM: St/Province: WK: Postal Code: Fax: E-Mail: Other: ANNUAL MEMBERSHIP CLASSIFICATION c Patient................................................. $55 c Donor................................................ $500 c Advocate............................................. $55 c Sponsor...........................................$1000 c Professional...................................... $100 c Corporate........................................$5000 c Other...................................... $________ c Anonymous...........................$________ c Include me as a PAACT member, although I currently cannot contribute Tribute gifts support the daily operations of PAACT, Inc., by furnishing PC patients, doctors and advocates with the latest information available on the methods of detection, diagnostic procedures, evaluation and treatments for prostate cancer. We also participate in matching gift programs and United Way. For more information contact us at (616) 453-1477. c Check Enclosed c Charge to my credit card (below): c MC c VISA c Discover c American Express Enclosed is $ ________________________________________________, In memory of Lloyd J. Ney, Sr. Enclosed is $ ________________________________________________, for PAACT’s general operation expenses. Enclosed is $ ________________________________________________, I wish to remain anonymous. In Memory of ___________________________________________________________________________________________ Please send acknowledgement card to: Name __________________________________________________________________________________________________ Address_________________________________________________________________________________________________ City_________________________________________________State____________________Zip________________________ Account Number: ________________________________________________ Amount $ _______________________________ Signature: ______________________________________________________Expiration Date: ___________________________