2nd Annual Prostate Cancer Forum PowerPoint Presentation

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“Fighting Cancer: It’s All We Do.”™

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Management of the Prostate Cancer Patient: Surveillance and Relapse Ulka Vaishampayan M.D. Chair, GU Multidisciplinary team Associate Professor Of Medicine Detroit Medical Center Wayne State University/ Karmanos Cancer Institute, Detroit MI.

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Relapse post RP Post surgery follow pts for symptoms such as incontinence or impotence. PSA level to be followed every 3 months depending on level of risk. Pathology report, every patient should ask for a copy and KEEP it for future reference. If positive margins, or extracapsular involvement consider Radiation therapy after surgery. If seminal vesicle involvement or lymph node involvement consider hormone therapy.

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Relapse post RT Consider cryo therapy if: Prolonged time between initial RT and relapse Low PSA level Prostate enlargement or nodule palpable Biopsy of prostate reveals active disease No metastasis on staging scans. Otherwise consider clinical trial or standard therapy which is androgen deprivation therapy.

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Therapy questions Hormone therapy questions: When to start? Continuous vs intermittent Which kind: Lupron/Zoladex with casodex or casodex alone (50 mg daily) or casodex and finasteride or high dose casodex 150 mg daily? Should we stop treatment when it stops working? What are the risks?

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Common Complications of Hormone Therapy Fatigue Metabolic syndrome- high blood sugar, high cholesterol Increased risk of heart problems in people who have heart disease Hot flashes Impotence Osteoporosis Gynecomastia and breast tenderness Mood swings Liver toxicity Diarrhea, nausea

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Strategies to address side effects of hormone therapy Hormone therapy works by suppressing the male hormone/testosterone levels. Fighting the side effects: -Increased Awareness -Stay active - Healthy diet Ask for medication therapy for hot flashes if bothersome. Consider intermittent hormone therapy if feasible Monitor cholesterol, blood sugars periodically.

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Dietary factors Lycopene: A minimum of 2 servings (1 cup) per week of tomato sauce can reduce the risk of development and progression of prostate cancer. Cruciferous vegetables: at least five servings per week can decrease the risk of developing prostate cancer by 20%. Green Tea may have possible protective effects A large study showed that too much calcium (over 2000mg daily) can increase metastatic prostate cancer risk fivefold compared with those consuming <500 mg daily- Health Professionals Follow Up study

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Dietary factors Vitamins within the recommended daily intake are recommended Overdosage of vitamins maybe potentially harmful Male smokers study in Finland showed that Vitamin E supplementation decreased the incidence of prostate cancer by 32% and the mortality related to prostate cancer by 41%. Beta carotene (Vit A) increased risk of lung cancer Finasteride/Proscar prevented prostate cancer and reduced the risk by 25% Selenium and Vit E trial completed and no benefit noted.

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KCI: Novel agent studies in PSA relapse ca prostate Lycopene Isoflavones Curcumin DIM Atorvastatin+celecoxib Bevacizumab Muscadine (grape seed extract)

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Systemic Therapy in Treatment of Prostate Cancer Discuss use of systemic therapy in metastatic prostate cancer to a} Prolong life b} For symptom control In PSA relapse prostate cancer, the goal is to delay metastases and keep long term toxicity to a minimum

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Metastatic prostate cancer progressing after testosterone suppression therapy

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Development of Hormonal Escape Prostate Cancer. London, England: Times Mirror International Publishers Ltd;1996:143. Deprive androgen Cell numbers Time Androgen-independent cells take over Responsive Dependent Independent

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Persistent hormone sensitivity even after testosterone suppression! 10% of circulating testosterone remains after conventional androgen deprivation therapy. Conversion of adrenal hormones to testosterone Testosterone persists in prostate cancer microenvironment as shown in bone biopsies. Androgen receptor upregulation. (inhibitors such as enzalutamide/MDV-3100 work) Cyp17A, the enzyme that converts adrenal steroids to androgen is overexpressed in advanced prostate cancer, and in bone biopsies from metastatic sites. (inhibited by abiraterone) Hence prostate cancer remains dependent on testosterone even in the hormone refractory stage.

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16 CRPC Androgen-dependent cell ADPC, androgen-dependent prostate cancer Simple Model of the Evolution of CRPC

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17 Endocrine Testosterone testis Endocrine Androgen Dependent T T DHT T AR Intracrine Testosterone T DHT DHEA Others… AR adrenal cholesterol? Androgen (Ligand) Independent AR Dependent T DHT DHEA Others… AR adrenal Her2 IL6 Intracrine Androgen Dependent AR splice variants Src? Androgen and AR Independent T DHT DHEA Others… AR adrenal prostate cancer cells AR, androgen receptor Nelson P et al. Unpublished. Androgen and AR-defined Prostate Cancer Cell States

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FDA-Approved Chemotherapy 1980s 1990s 2005 Estramustine* Mitoxantrone + Prednisone Docetaxel + Prednisone *No longer recommended as a monotherapy. Food and Drug Administration. Website: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm. Accessed July 1, 2010; Prostate Cancer, v.1.2010, National Comprehensive Cancer Network. Website: http://www.nccn.org/professionals/physician_gls/PDF/prostate.pdf . Accessed July 1, 2010.

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TAX 327 Trial Results-1006 Pts Eisenberger et al. ASCO 2004, abstr#4

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Sipuleucel-T: Patient-Specific Therapy Day 1 Leukapheresis sipuleucel-T is manufactured Day 3-4 Patient is infused Apheresis Center Dendreon Doctor’s Office COMPLETE COURSE OF THERAPY: Weeks 0, 2, 4

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Randomized Phase 3 IMPACT Trial (IMmunotherapy Prostate AdenoCarcinoma Treatment) Primary endpoint: Overall Survival Secondary endpoint: Time to Objective Disease Progression

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Efficacy of Multiple Agents in Phase III Trials Post Docetaxel

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23 Normalization of Bone Scan With XL-184 Baseline Week 12 Bone scans at baseline and during therapy with XL184 Docetaxel-pretreated (n=10) Evidence of bone scan resolution (partial or complete) Maximum tumor change, per mRECIST Change in bone pain Change in tALP and PSA Maximum change in plasma CTx Best change in hemoglobin -88% NE Yes -41% Improvement Smith et al. EORTC; 2010.

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24 Metastatic Castration Resistant Sipuleucel-Tb 2nd-line hormones Docetaxel and pred Mitoxantrone c) a. selected patients b. level 1 evidence for survival c. level 1 evidence for palliation d. not yet FDA-approved Asymptomatic (chemotherapy naïve) Post Docetaxel Docetaxelb Mitoxantronec XRT, 89Src, 153Smc Radium-223b,c,d Symptomatic (chemotherapy naïve) Abirateroneb Cabazitaxelb (Sipuleucel-Ta,b) MDV3100b,d Radium-223b,c,d Mitoxantrone Treatment Paradigm for Metastatic CRPC –State of Art 2012 Adapted from Higano CS, Crawford ED. Urol Oncol, in press.

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Conclusions 2010-2012 have been bumper years for therapeutics of metastatic prostate cancer Provenge immunotherapy and cabazitaxel chemotherapy were FDA approved. Hormonal agents such as abiraterone and MDV-3100 are now FDA approved. Alpha particle radiation is awaiting approval. Targeted therapies such as XL-184 are showing preliminary exciting activity At KCI multiple clinical trials using these and other new agents are ongoing. Look for a study that works for you and benefits you!

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KCI: Novel agent studies in metastatic prostate cancer Abiraterone+/- novel agent to overcome resistance Alpharadin therapy expanded access trial MDV-3100/Enzalutamide XL-184 vs mitoxantrone Chemotherapy + novel agent to overcome resistance

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Restoring Quality of Life After Prostate Surgery Steven M Lucas, MD Assistant professor Department of Urology Wayne State University School of Medicine Karmanos Cancer Institute

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Restoring quality of life Recovering from immediate treatment side effects Managing chronic symptoms related to treatment Can be separated into 2 components

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Early Postoperative Recovery Pain Abdominal distention Catheter in place Decreased activity Problems

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Early Recovery Pain: home on oral pain meds 1-3d Bowel function: Early ambulation Stool softeners / laxatives Catheter: removed in 7-10d Activity Ambulation by discharge Light activity at 2 weeks Start strenuous activity at 4 weeks

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Later effects from prostate therapy Urine Control Erection Function

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Urinary Continence after prostatectomy Novaro G, et al. J Urol 2010

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Early urinary control Urinary control improves with time Ko, YH et al, J Urol 2012

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Regaining urinary control- An active process Kegel Exercises: contract pelvic floor muscles without holding breath or contracting abdominal or thigh muscles 3 daily sessions: 1 each lying, sitting, standing 15 repetitions Contract 2-10s and relax for same Increase by 1-2 sec each wk up to 10-20 sec

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Management of early urinary control Comparison of men who underwent organized program of Kegel exercises versus those that did not (16 in each group) Tienforti et al, BJU, 2012

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Early Urinary Control Biofeedback training Perform Kegel maneuvers in clinic setting EMG patches monitor effectiveness Electrical floor stimulation Probe inserted into rectum sends pulse to stimulate pelvic floor nerves and muscles

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Medications Generally act to control bladder overactivity Anticholinergics: ditropan Imipramine

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Other factors that may affect urinary control Age Weight Previous urinary control Prostate size Intravesicular lobe

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Urinary Incontinence- Surgery Slings Artificial Sphincters

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Erectile dysfunction Recovery of erections after prostate cancer treatment improves with time Medications and medical devices can be used to help improve recovery of erections

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Factors Influencing Recovery of Erections Erection Function Following Treatment Determined by… Age Comorbidities Preoperative erection function PSA Nerve-sparing Alemozaffar et al, JAMA, 2011

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Penile rehabilitation Period of time where unable to have erections Promote blood flow to penis to enhance healing and prevent fibrosis. Management of Erectile Dysfunction

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Rehabilitation Program Phosphodiesterase inhibitor Viagra, cialis, levitra 3 times per week, once daily Vacuum Erection device Once daily Penile injections Alprostadil, papaverine, phentolamine Urethral suppositories

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Who tends to participate? What determines success? 676 patients 54% participated Factors influencing participation Increased: African American Good function before treatment Decreased: High preTx PSA Additional cancer therapy Factors influencing Outcome Decreased recovery of function Age Additional cancer therapy Kimura et al, BJU, 2012

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Vacuum Erection Device Advantage One time cost Can work for those not responding to medications Disadvantage Cumbersome

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Surgical Treatment of Erectile Dysfunction Inflatable Malleable

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Conclusion Restoration of quality of life in the early postoperative period requires preparation and prevention Prevention and more invasive therapies may be needed to manage chronic or late side effects

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Ruthie Maples, MSW, LMSW, ACSW Karmanos Cancer Institute Kathryn Smolinski, MSW, JD Wayne State University Karmanos Cancer Institute

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Understanding and Responding to the Legal and Psychosocial Needs of Prostate Cancer Patients and Their Families

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STRESS

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Psychological Reactions to Diagnosis, Treatment Selection, and Treatment At time of diagnosis: Concerns and worries of having cancer How will it affect my work, activities and hobbies? How will my family react? How will I have to change my lifestyle? Will my health insurance cover the expenses? How will this all turn out?

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Psychological Reactions to Diagnosis, Treatment Selection, and Treatment At time of treatment selection: “the sense of having to choose between quality of life and longevity” Considering second opinions about tx options Anxiety about information overload: Your health care team Friends and family The Internet

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Psychological Reactions to Diagnosis, Treatment Selection, and Treatment During and after treatment: Side effects such as: hot flashes, osteoporosis, anemia, ED, fatigue etc. can cause distress Anxiety tends to be the most often experienced symptom for men with prostate cancer Many men may also report irritability or depression Concerns about pain and quality of life

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Support by Caregivers and Family for the Prostate Cancer Patient Anticipating and implementing changes in his lifestyle due to side effects of treatment Incontinence Erectile dysfunction As a caregiver, be sure to take care of yourself as well Source: http://www.ustoo.org/Family_Intro.asp?type=2

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How Oncology Social Workers Can Help Helping you identify and access your support system Helping you and your family adjust to changes Teaching effective communication skills Providing opportunities for you to discuss concerns Providing community resources Taking time to help you navigate the complex health system Assistance obtaining medications and other benefits

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Do Cancer Patients Ever Worry About Legal Issues? Source: Cancer Legal Resource Center http://www.disabilityrightslegalcenter.org/about/documents/CLRCTALStatistics2010.pdf 2010 Telephone Assistance Line – Top 8 Legal Issues Employment Health Insurance Disability Treatment Financial Quality of Estate Insurance Navigation Insurance Assistance Assistance Care Planning 700 600 500 400 300 200 100 0

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Legal Advocacy for People with Cancer LAPC is a partnership between Karmanos Cancer Center and Wayne State University Disability Law Clinic It is designed to provide legal information, resources, and representation to low-income cancer patients at Karmanos who are otherwise unable to afford legal services

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What Can a Lawyer Do? I can HELP I - Insurance Coverage (Health Insurance) H - Housing (Eviction, Utility Shut-off, Foreclosure) E - Employment (Discrimination, FMLA, Disability) L - Legal Planning (Advance Directives, Wills, Powers of Attorney) P - Public Benefits (Medicaid, Social Security Disability, Supplemental Security Income (SSI))

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Insurance Coverage Issues Is it right that my employer has dropped my coverage? What do I do if I cannot work anymore but need to continue my health insurance? What if I never had health insurance? Can I get it? Is anyone legally obligated to provide me coverage? Should I pay this bill even if I don’t understand the charges? What about collections?

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Housing Issues Utilities – can they just turn them off because I stopped paying? Landlords – do they have to keep my apartment habitable? Eviction – does my landlord Foreclosure – there are programs to assist you

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Employment Issues Am I legally obligated to tell my employer that I have cancer? Can I be fired for having cancer? If I need to take a leave of absence, are there laws to protect my job? Does my employer need to accommodate me at work?

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Legal Planning How can someone help me pay my bills when I am in the hospital? I have never made a will, should I do it now? Who will make treatment decisions if I can’t make them for myself? Is it even helpful for me to be thinking about these things?

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Public Benefits What are the state and federal disability programs available to me? How do I do if I have been denied benefits? What happens if I think that Medicaid or my Bridge Card were cut off for no reason? Can anyone explain this letter from SSA for me?

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Questions? Need more information? If you would like to talk with someone about specific questions you may have: Stop by the Cancer Connection Café held twice a week in the Karmanos Lobby Schedule an appointment to talk with someone from KCC Social Work and Supportive Services at (313) 576-9700 Legal Advocacy for People with Cancer at (313) 577-9911