“fighting cancer: it’s all we do.” ™. management of the prostate cancer patient:...

“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


and/or Salvage Protocol



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


P<0.0001HR= 0.70

MDV-3100Placebo


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


Ruthie Maples, MSW, LMSW, ACSWKarmanos Cancer Institute

Kathryn Smolinski, MSW, JD Wayne State UniversityKarmanos Cancer Institute


Understanding and Responding to the Legal and Psychosocial Needs

of Prostate Cancer Patients and Their Families


STRESS


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?


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


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


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


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


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

700

600

500

400

300

200

100

0


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


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))


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?


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


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?


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?


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?


Questions? Need more information?

“fighting cancer: it’s all we do.” ™. management of the prostate cancer patient:...

Documents

prostate cancer patient

progression of prostate

incidence of prostate

medication therapy

cryo therapy

radiation therapy

standard therapy

metastatic prostate