“Fighting Cancer: It’s All We Do.”™
Management of the Prostate Management of the Prostate Cancer Patient: Surveillance and Cancer Patient: Surveillance and
RelapseRelapse
Ulka Vaishampayan M.D.Chair, GU Multidisciplinary teamAssociate Professor Of Medicine
Detroit Medical CenterWayne State University/ Karmanos Cancer Institute,
Detroit MI.
Relapse post RPRelapse 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.
Relapse post RT Relapse post RT
• Consider cryo therapy if:a) Prolonged time between initial RT and relapseb) Low PSA levelc) Prostate enlargement or nodule palpabled) Biopsy of prostate reveals active diseasee) No metastasis on staging scans.
Otherwise consider clinical trial or standard therapy which is androgen deprivation therapy.
Therapy questionsTherapy 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?
Common Complications of Common Complications of Hormone TherapyHormone 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
Strategies to address side effects of Strategies to address side effects of hormone therapyhormone 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.
Dietary factorsDietary 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
Dietary factorsDietary 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.
KCI: Novel agent studies in PSA KCI: Novel agent studies in PSA relapse ca prostaterelapse ca prostate
• Lycopene• Isoflavones• Curcumin• DIM• Atorvastatin+celecoxib• Bevacizumab• Muscadine (grape seed extract)
Systemic Therapy in Treatment of Systemic Therapy in Treatment of Prostate CancerProstate Cancer
– Discuss use of systemic therapy in metastatic prostate cancer toa} Prolong lifeb} For symptom control
– In PSA relapse prostate cancer, the goal is to delay metastases and keep long term toxicity to a minimum
Metastatic prostate cancer Metastatic prostate cancer progressing after testosterone progressing after testosterone
suppression therapysuppression therapy
Chemo
Immunotherapy
Hormones
Prostate ca
Development of Hormonal EscapeDevelopment of Hormonal Escape
Prostate Cancer. London, England: Times Mirror International Publishers Ltd;1996:143.
Depriveandrogen
Cel
l num
bers
Time
Androgen-independentcells take over
Responsive
Dependent
Independent
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.
16
CRPC
Androgen-dependent cell
ADPC, androgen-dependent prostate cancer
Simple Model of the Evolution of Simple Model of the Evolution of CRPCCRPC
17
EndocrineTestosterone
testis
Endocrine Androgen Dependent
TT DHT
T
AR
IntracrineTestosterone
T DHT
DHEAOthers…
AR
adrenal
cholesterol?
Androgen (Ligand) IndependentAR Dependent
T DHT
DHEAOthers…
AR
adrenal
Her2 IL6
Intracrine Androgen Dependent
AR splice variants
Src?
Androgen and AR Independent
T DHT
DHEAOthers…
AR
adrenal
prostate cancer cells
AR, androgen receptorNelson P et al. Unpublished.
Androgen and AR-defined Androgen and AR-defined Prostate Cancer Cell StatesProstate Cancer Cell States
FDA-Approved ChemotherapyFDA-Approved Chemotherapy
1980s 1990s 2005
Estramustine* Mitoxantrone +
PrednisoneDocetaxel
+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.
TAX 327 Trial Results-1006 PtsTAX 327 Trial Results-1006 PtsMitox + Pred12mg/m2 Q 3 weeks
Docetaxel + Pred75mg/m2 Q 3weeks
Docetaxel + Pred30mg/m2 weekly 5/6
Pain response 22% 35% (p=0.01) 31% (p=0.08)
Response rate (PSA)
32% 45% (p=0.0005) 48% (p=0.0001)
Grade 3/4 neutropenia
21.7% 32% 1.5%
Median survival
16.5 months 18.9 months (p=0.009)
17.4 months(p=0.36)
Eisenberger et al. ASCO 2004, abstr#4Eisenberger et al. ASCO 2004, abstr#4
Sipuleucel-T: Patient-Specific TherapySipuleucel-T: Patient-Specific Therapy
Day 1
Leukapheresissipuleucel-T is manufactured
Day 3-4Patient is infused
Apheresis Center Dendreon Doctor’s Office
COMPLETE COURSE OF THERAPY:Weeks 0, 2, 4
Randomized Phase 3 IMPACT TrialRandomized Phase 3 IMPACT Trial(IMmunotherapy Prostate AdenoCarcinoma (IMmunotherapy Prostate AdenoCarcinoma
Treatment)Treatment)
Primary endpoint: Overall SurvivalSecondary endpoint: Time to Objective Disease
Progression
Asymptomatic or Minimally
Symptomatic Metastatic Castrate Resistant
Prostate Cancer (N=512)
Asymptomatic or Minimally
Symptomatic Metastatic Castrate Resistant
Prostate Cancer (N=512)
Placebo Q 2 weeks
x 3
Placebo Q 2 weeks
x 3
Sipuleucel-T Q 2 weeks x 3
Sipuleucel-T Q 2 weeks x 3
P R O
G R E S
S I O N
P R O
G R E S
S I O N
2:1
SURVIVAL
SURVIVAL
Treated at Physician discretion
and/or Salvage Protocol
Treated at Physician discretion
and/or Salvage Protocol
Treated at Physician discretion
Treated at Physician discretion
Efficacy of Multiple Agents in Phase III Trials Post Docetaxel
Agent Med survival P valueHazard ratio
Abiraterone + PredPlacebo + Pred
15.8 months11.2 months
P<0.0001HR= 0.74
Cabazitaxel+ predMitoxantrone + pred
15.1 months12.7 months
P<0.0001HR= 0.70
MDV-3100Placebo
18.4 months13.6 months
P<0.0001HR= 0.631
Alpharadin/RAD-223)Placebo
14 months11.2 months
p = 0.0022HR= 0.699
23
Normalization of Bone Scan With Normalization of Bone Scan With XL-184XL-184
Baseline Week 12
Bone scans at baseline andduring therapy with XL184
Docetaxel-pretreated (n=10)
Evidence of bone scanresolution (partial or complete)
Maximum tumor change, per mRECIST
Change in bone pain
Change in tALPand PSA
Maximum change inplasma CTx
Best change in hemoglobin
-88%
NE
Yes
-41%
Improvement
Weeks on StudyScr 0 5 10 15 20
0
200
400
600
800
1000
0
100
200
300
400
5000tALPPSA
PS
A
tAL
P
Smith et al. EORTC; 2010.
24
Metastatic Castration Resistant
Sipuleucel-Tb
2nd-line hormonesDocetaxel 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 Treatment Paradigm for Metastatic CRPC –State of Art 2012CRPC –State of Art 2012
Adapted from Higano CS, Crawford ED. Urol Oncol, in press.
ConclusionsConclusions
• 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!
KCI: Novel agent studies in KCI: Novel agent studies in metastatic prostate cancermetastatic 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
2nd Annual Prostate Cancer ForumSeptember 22, 2012 • Charles H. Wright Museum of African American History • Detroit, MI
Restoring Quality of Life After Prostate SurgerySteven M Lucas, MD
Assistant professorDepartment of UrologyWayne State University School of MedicineKarmanos Cancer Institute
Restoring quality of life
• Recovering from immediate treatment side effects
• Managing chronic symptoms related to treatment
Can be separated into 2 components
Early Postoperative Recovery
• Pain • Abdominal distention• Catheter in place• Decreased activity
Problems
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
Later effects from prostate therapy
Urine Control Erection Function
Urinary Continence after prostatectomy
Novaro G, et al. J Urol 2010
Early urinary control• Urinary control improves with time
Ko, YH et al, J Urol 2012
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
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
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
Medications
• Generally act to control bladder overactivity– Anticholinergics: ditropan– Imipramine
Other factors that may affect urinary control
– Age– Weight– Previous urinary control– Prostate size– Intravesicular lobe
Urinary Incontinence- SurgerySlings Artificial Sphincters
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
Factors Influencing Recovery of Erections
Erection Function Following Treatment Determined by…AgeComorbiditiesPreoperative erection functionPSANerve-sparing
Alemozaffar et al, JAMA, 2011
• 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
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
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
Vacuum Erection Device
• Advantage– One time cost– Can work for those not responding to medications
• Disadvantage– Cumbersome
Surgical Treatment of Erectile Dysfunction
Inflatable Malleable
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
2nd Annual Prostate Cancer ForumSeptember 22, 2012 • Charles H. Wright Museum of African American History • Detroit, MI
Ruthie Maples, MSW, LMSW, ACSWKarmanos Cancer Institute
Kathryn Smolinski, MSW, JD Wayne State UniversityKarmanos Cancer Institute
2nd Annual Prostate Cancer ForumSeptember 22, 2012 • Charles H. Wright Museum of African American History • Detroit, MI
Understanding and Responding to the Legal and Psychosocial Needs
of Prostate Cancer Patients and Their Families
2nd Annual Prostate Cancer ForumSeptember 22, 2012 • Charles H. Wright Museum of African American History • Detroit, MI
STRESS
2nd Annual Prostate Cancer ForumSeptember 22, 2012 • Charles H. Wright Museum of African American History • Detroit, MI
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?
2nd Annual Prostate Cancer ForumSeptember 22, 2012 • Charles H. Wright Museum of African American History • Detroit, MI
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
2nd Annual Prostate Cancer ForumSeptember 22, 2012 • Charles H. Wright Museum of African American History • Detroit, MI
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
2nd Annual Prostate Cancer ForumSeptember 22, 2012 • Charles H. Wright Museum of African American History • Detroit, MI
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
2nd Annual Prostate Cancer ForumSeptember 22, 2012 • Charles H. Wright Museum of African American History • Detroit, MI
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
2nd Annual Prostate Cancer ForumSeptember 22, 2012 • Charles H. Wright Museum of African American History • Detroit, MI
Do Cancer Patients Ever Worry About Legal Issues?
Source: Cancer Legal Resource Centerhttp://www.disabilityrightslegalcenter.org/about/documents/CLRCTALStatistics2010.pdf
2010 Telephone Assistance Line – Top 8 Legal Issues
Employment Health Insurance Disability Treatment Financial Quality of EstateInsurance Navigation Insurance Assistance Assistance Care Planning
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2nd Annual Prostate Cancer ForumSeptember 22, 2012 • Charles H. Wright Museum of African American History • Detroit, MI
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
2nd Annual Prostate Cancer ForumSeptember 22, 2012 • Charles H. Wright Museum of African American History • Detroit, MI
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))
2nd Annual Prostate Cancer ForumSeptember 22, 2012 • Charles H. Wright Museum of African American History • Detroit, MI
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?
2nd Annual Prostate Cancer ForumSeptember 22, 2012 • Charles H. Wright Museum of African American History • Detroit, MI
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
2nd Annual Prostate Cancer ForumSeptember 22, 2012 • Charles H. Wright Museum of African American History • Detroit, MI
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?
2nd Annual Prostate Cancer ForumSeptember 22, 2012 • Charles H. Wright Museum of African American History • Detroit, MI
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?
2nd Annual Prostate Cancer ForumSeptember 22, 2012 • Charles H. Wright Museum of African American History • Detroit, MI
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 Cardwere cut off for no reason?
• Can anyone explain this letter from SSA for me?
2nd Annual Prostate Cancer ForumSeptember 22, 2012 • Charles H. Wright Museum of African American History • Detroit, MI
Questions? Need more information?