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“Fighting Cancer: It’s All We Do.”™
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.
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.
Relapse post RT
• Consider cryo therapy if:
a) Prolonged time between initial RT and relapse
b) Low PSA level
c) Prostate enlargement or nodule palpable
d) Biopsy of prostate reveals active disease
e) No metastasis on staging scans.
Otherwise consider clinical trial or standard therapy
which is androgen deprivation therapy.
Therapy questions
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•
•
•
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
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
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.
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
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.
KCI: Novel agent studies in PSA
relapse ca prostate
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•
•
•
•
•
•
Lycopene
Isoflavones
Curcumin
DIM
Atorvastatin+celecoxib
Bevacizumab
Muscadine (grape seed extract)
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
Metastatic prostate cancer
progressing after testosterone
suppression therapy
Immunotherapy
Prostate ca
Chemo
Hormones
Development of Hormonal Escape
Cell numbers
Deprive
androgen
Androgen-independent
cells take over
Responsive
Dependent
Independent
Time
Prostate Cancer. London, England: Times Mirror International Publishers Ltd;1996:143.
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.
Simple Model of the Evolution of
CRPC
Androgen-dependent cell
CRPC
ADPC, androgen-dependent prostate cancer
16
Androgen and AR-defined
Prostate Cancer Cell States
Endocrine
Androgen
Dependent
Intracrine
Androgen
Dependent
prostate cancer cells
Intracrine
Testosterone
DHT
T
T
Endocrine
Testosterone
testis
AR, androgen receptor
Nelson P et al. Unpublished.
Androgen
and AR
Independent
AR splice
variants
Her2 IL6
AR
AR
T
Androgen
(Ligand)
Independent
AR Dependent
T
DHT
cholesterol?
DHEA
Others…
adrenal
AR Src?
T DHT
AR
T
DHEA
Others…
DHT
DHEA
Others…
adrenal
adrenal
17
FDA-Approved Chemotherapy
1980s
Estramustine*
1990s
Mitoxantrone
+
Prednisone
2005
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.
TAX 327 Trial Results-1006 Pts
Mitox + Pred
12mg/m2
Q 3 weeks
Docetaxel + Pred
75mg/m2
Q 3weeks
Docetaxel + Pred
30mg/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#4
Sipuleucel-T: Patient-Specific Therapy
Day 1
Leukapheresis
Apheresis Center
sipuleucel-T is
manufactured
Dendreon
Day 3-4
Patient is infused
Doctor’s Office
COMPLETE COURSE OF THERAPY:
Weeks 0, 2, 4
Randomized Phase 3 IMPACT Trial
(IMmunotherapy Prostate AdenoCarcinoma
Treatment)
Asymptomatic or
Minimally
Symptomatic
Metastatic
Castrate
Resistant
Prostate Cancer
(N=512)
Primary endpoint:
Secondary endpoint:
Sipuleucel-T
Q 2 weeks x 3
2:1
Placebo
Q 2 weeks x 3
P
R
O
G
R
E
S
S
I
O
N
Overall Survival
Time to Objective Disease
Progression
Treated at
Physician
discretion
Treated at
Physician
discretion
and/or Salvage
Protocol
S
U
R
V
I
V
A
L
Efficacy of Multiple Agents in Phase III
Trials Post Docetaxel
Agent
Med survival
P value
Hazard ratio
Abiraterone + Pred
Placebo + Pred
15.8 months
11.2 months
P<0.0001
HR= 0.74
Cabazitaxel+ pred
15.1 months
Mitoxantrone + pred 12.7 months
P<0.0001
HR= 0.70
MDV-3100
Placebo
18.4 months
13.6 months
P<0.0001
HR= 0.631
Alpharadin/RAD223)
Placebo
14 months
11.2 months
p = 0.0022
HR= 0.699
Normalization of Bone Scan With
XL-184
Docetaxel-pretreated (n=10)
Baseline
Week 12
Evidence of bone scan
resolution (partial or complete)
Yes
Maximum tumor change,
per mRECIST
-41%
Change in bone pain
Bone scans at baseline and
during therapy with XL184
Smith et al. EORTC; 2010.
tALP
PSA
tALP
1000
800
600
400
200
0
Maximum change in
plasma CTx
Best change in hemoglobin
5000
400
300
200
100
0
PSA
Change in tALP
and PSA
Improvement
Scr 0 5 10 15 20
Weeks on Study
-88%
NE
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Treatment Paradigm for Metastatic
CRPC –State of Art 2012
Metastatic Castration Resistant
Asymptomatic
(chemotherapy naïve)
Sipuleucel-Tb
2nd-line hormones
Docetaxel and pred
Mitoxantrone c)
Symptomatic
(chemotherapy naïve)
Post Docetaxel
Docetaxelb
Mitoxantronec
XRT, 89Src, 153Smc
Radium-223b,c,d
Abirateroneb
Cabazitaxelb
(Sipuleucel-Ta,b)
MDV3100b,d
Radium-223b,c,d
Mitoxantrone
a. selected patients b. level 1 evidence for survival c. level 1 evidence for palliation
d. not yet FDA-approved
Adapted from Higano CS, Crawford ED. Urol Oncol, in press.
24
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!
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
2nd Annual Prostate Cancer Forum
September 22, 2012 • Charles H. Wright Museum of African American History • Detroit, MI
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
Restoring quality of life
Can be separated into 2 components
• Recovering from immediate treatment side effects
• Managing chronic symptoms related to treatment
Early Postoperative Recovery
Problems
• Pain
• Abdominal distention
• Catheter in place
• Decreased activity
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- Surgery
Slings
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…
Age
Comorbidities
Preoperative erection function
PSA
Nerve-sparing
Alemozaffar et al, JAMA, 2011
Management of Erectile Dysfunction
• Penile rehabilitation
– Period of time where unable to have erections
– Promote blood flow to penis to enhance healing
and prevent fibrosis.
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 Forum
September 22, 2012 • Charles H. Wright Museum of African American History • Detroit, MI
Ruthie Maples, MSW, LMSW, ACSW
Karmanos Cancer Institute
Kathryn Smolinski, MSW, JD
Wayne State University
Karmanos Cancer Institute
2nd Annual Prostate Cancer Forum
September 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 Forum
September 22, 2012 • Charles H. Wright Museum of African American History • Detroit, MI
STRESS
2nd Annual Prostate Cancer Forum
September 22, 2012 • Charles H. Wright Museum of African American History • Detroit, MI
Psychological Reactions to Diagnosis,
Treatment Selection, and Treatment
• At time of diagnosis:
•
•
•
•
•
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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 Forum
September 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 Forum
September 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 Forum
September 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 Forum
September 22, 2012 • Charles H. Wright Museum of African American History • Detroit, MI
How Oncology Social Workers Can Help
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•
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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 Forum
September 22, 2012 • Charles H. Wright Museum of African American History • Detroit, MI
Do Cancer Patients Ever Worry
About Legal Issues?
2010 Telephone Assistance Line – Top 8 Legal Issues
700
600
500
400
300
200
100
0
Employment
Health
Insurance
Insurance
Navigation
Disability Treatment Financial
Quality of
Insurance Assistance Assistance Care
Estate
Planning
Source:
Cancer Legal Resource Center
http://www.disabilityrightslegalcenter.org/about/documents/CLRCTALStatistics2010.pdf
2nd Annual Prostate Cancer Forum
September 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 Forum
September 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 Forum
September 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 Forum
September 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 Forum
September 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 Forum
September 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 Forum
September 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 Card
were cut off for no reason?
• Can anyone explain this letter from SSA for me?
2nd Annual Prostate Cancer Forum
September 22, 2012 • Charles H. Wright Museum of African American History • Detroit, MI
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