"Creating a Prostate Cancer Center of Excellence"
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"Creating a Prostate Cancer Center of
Excellence"Paul Sieber MD FACS
Lancaster Urology
ADT Clinic• Why 1. Consistency of care 2. Improved outcomes 3. Better economics• What does it take 1. Discipline 2. Mid-level providers 3. Planning• Who cares 1. Insurers 2. Patients• How 1. Implementation
Bone Clinic
Journal of UrologyFebruary 1997
Osteoporosis after Orchiectomy for Prostate Cancer
Harry W Daniell UC Davis, Department of Family Practice First article attributing orchiectomy with
accelerated osteoporosis and questions risks to long term survivors.
ADT and Fracture Risk
Author Population
N FractureIncidence
Time
Smith Pharmacybenefit
3779 15.1% 22 months
Oefelein Community
181 20% 10 years
Shahinian SEER 14,394 19.4 1-5 years Krupski Medicare 716 45.5% 7 yearsMelton Rochester 429 73% 15 years
ADT Is Associated With Fracture
• In men surviving at least 5 years after diagnosis:– Of those receiving ADT, 19.4% experienced a fracture– Of those NOT receiving ADT, 12.6% experienced a fracture– ADT resulted in an excess risk of fracture of 45%
Shahinian VB, et al. N Engl J Med. 2005;352:154-164.
No ADT (n = 32,931)GnRH agonist, 1–4 doses (n = 3763)GnRH agonist, 5–8 doses (n = 2171)GnRH agonist, ≥ 9 doses (n = 5061)Orchiectomy (n = 3399)
Years After Diagnosis2 3 4 5 6 7 8 9 101
Una
djus
ted
Frac
ture
-Fre
e Su
rviv
al (
%)
0
100908070605040302010
ADT-Related Fracture-Free Survival
Fractures in Men Receiving ADT and Survival
Oefelein MG, et al. J Urol. 2002:168:1005-1007; Department of Health and Human Services. A report of the Surgeon General. 2004.
0 20 40 60 80 100 120 140 160 180 200Months
0.10.20.30.40.50.60.70.80.91.0
Cum
ulat
ive
Prop
orti
on
Surv
ivin
g
History of fracture (n = 24)No history of fracture (n = 171) P = 0.04
• In men receiving ADT for prostate cancer, median overall survival was reduced in those who sustained a skeletal fracture since diagnosis of prostate cancer (121 vs 160 months, P = 0.04)
• Skeletal fracture was a negative predictor of survival (Relative Death Risk = 7.4, P = 0.007)
Bone Clinic Protocol• 1. All patients on ADT seen by mid-
level at least yearly• 2. All patients undergo DEXA• 3. All patients have metabolic studies• 4 All patients assessed/counseled for
risk: FRAX,fall,glasses,smoking,EtOH consumption,calcium/vitamin D
Screening for Bone Loss• DXA(Dual X-ray Absorptiometry) =
Gold Standard• Total hip, femoral neck and lumbar
spine standard areas of interest• Heel ultrasound, finger or forearm
DXA, and quantitative CT other options but numerous weaknesses
Metabolic workup• CMP, CBC, Vitamin D minimum• Stone formers 24 hour urine• Options; TSH, evaluate for GI
malabsorption, Endocrine consult
TREATMENT DECISION• 2 clinical trials with level 1 evidence of
both BMD and fracture reduction• Patient population included men< 70
with osteopenia and >70 without regard to BMD
• NOF recommends treat osteoporosis follow FRAX for others
• What is risk level for osteopenics on ADT
BMD vs Fracture Rate & Incidence
>1.0 1.0 to 0.5 0.5 to 0.0 0.0 to -0.5
-0.5 to -1.0
-1.0 to -1.5
-1.5 to -2.0
-2.0 to -2.5
-2.5 to -3.0
-3.0 to -3.5
<-3.50
5
10
15
20
25
30
35
40
45
50
0
50
100
150
200
250
300
350
400
450
Fracture Rate
No. of fractures
BMD
Frac
ture
Rat
eN
o. of Fractures
BMD
Minimum treatment• Ensure adequate calcium/vitamin D
intake 1200/800• Vitamin D >30• Reduce alcohol, smoking cessation,
and weight bearing exercises• Fall reduction strategies
Pharmacologic Therapy• 1. Prolia-RANK ligand monoclonal antibody • 2.
Aledronate(Fosamax).Risedronate(Actonel)
• 2. Zoledronic acid(Zometa,Reclast)• 2.Raloxifene(Evista)• 3.? Teriparatide(Forteo) blackbox warning
with radiation therapy• 3. Calcitonin(Miacalcin) no data in men
Clinical Impact of Low Testosterone Levels: Two Peer-Reviewed Articles
Perachino et al – BJUI. 2009
Morote et al – Urology. 2007
Testosterone Escapes OccurFrequently During LHRH Agonist Therapy
Adapted from Morote J et al. J Urol. 2007;178:1290–5
Serum testosterone
Survival-Free of AIP According toSerum Testosterone Behavior
Adapted from Morote J et al. J Urol. 2007;178:1290–5
Testosterone increases Group 1: <20 ng/dL Group 2: 20–50 ng/dLGroup 3: >50 ng/dL
0 24 48 72 96 120 144 168 192 216 240Months under ADT
0.0
0.2
0.4
0.6
0.8
1.0
Group 3 (72 months)
Group 2 (90 months)
P=0.0207
Group 1 (106 months)
Cum
ulat
ive
surv
ival
free
of P
SA p
rogr
essi
on
AIP, androgen-independent progression
Higher 6-Month Testosterone Levels Increase Risk of Death by 1.33 Times
Variable Coefficient (SEM)
Coefficient/SEM Hazard ratio(95% CI)
P value
Age, years 0.0359 (0.0200) 1.795 1.037(0.996–1.078) 0.08
Gleason score 0.3301 (0.1002) 3.295 1.391(1.141–1.696) <0.01
Ln (6-month PSA level) 0.2690 (0.0492) 5.468 1.309
(1.187–1.443) <0.01
(6-month testosterone)2 0.2874 (0.1190) 2.415 1.333
(1.053–1.687) <0.05
Predictors of survival probability (Cox regression model)
Perachino M et al. B J U Int 2010; 105(5); 648-51
SEM, standard error of the mean; Ln, natural logarithm
Goserelin 10.8 mg every 3 months; bone-only prostate cancer patients (N=117)
Bone Clinic
ADT Clinic
21
Urologists Provided Most Overall Healthcare Services to Patients with Prostate Cancer Over the Course of Disease Progression
% P
rost
ate
Can
cer H
ealth
Ser
vice
s
Initial Care Continuing Care
End of Life Care
Overall Care
*Medical oncology and hematology/oncology†Internal medicine, family practice and general practiceSkolarus 2010 J Urol 184:2279-2284
0
10
20
30
40
50
60
36.9
56.5
29.7
45.2
27.4
5.5 5.7
14.4
2.6
9.8
31.4
9.6
3.25.5
9.3
5.1
25.7
Urologists Radiation oncologists Medical oncologists* Primary care provider Other
†
• Initial care: first 12 months after diagnosis
• Continuing care: between initial and end of life
• End of life care: final 12 months of life
Abbreviation: LHRH=luteinizing hormone-releasing hormone.
Natural History of Prostate Cancer
• Typical presentation of patients as they move through the different stages. The line represents level burden of disease. Time is not proportional
Under the care of ONCOLOGIST
Castration Sensitive
Asymptomatic
Non Metastatic
Castration Resistant
Metastatic
Symptomatic
Local Therapy
Androgen Deprivation
Therapies After LHRH Agonists and Antiandrogen
Chemotherapy
Post Chemo
Death
New Paradigms 1.Bone Agents Xgeva ?Radium 223 2. Provenge 3. Abiraterone 4. Enzulutamide
Metastatic Disease• Detection of previously unidentified
metastatic disease as a leading cause of screening failure in a phase III trial of zibotentan versus placebo in patients with nonmetastatic, castration resistant prostate cancer.
• Yu EY J Urol July 2012• 31% of men with apparent M0 disease
were M1
Bone Metastasis• Denosumab and bone-
metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial.
Smith MR et al Lancet Jan 2012 396 23% of men with apparent MO
disease were M1
Provenge SurvivalBaseline PSA
<22.1 >22.1-50.1 >50.1-134.1
>134.1
Provenge OS
41.3mon 27.1mon 20.4mon 18.4mon
Control OS 28.3mon 20.1mon 15.0mon 15.6mon
Chodak G ASCO 2012 Abstract 4648
Prior SRE Associated with Greater Risk of Subsequent SRE
No prior SRE Prior SRE0
0.5
1
1.5
2
2.5
3
Saad F Clin GU Cancer 5:390-6
ADT Clinic• Bone Clinic plus 1. ROS for side effects 2. Additional labs include annual CBC,CMP,HgbA1c,Lipid profile 3. PSA doubling time if appropriate 4. Update to PCP
Keys to Success• Physician champion• Motivated mid-level as well• Group Buy-in• Make it easy for group members
William Penn“Liberty without discipline equals
chaosDiscipline without liberty equals
slavery”
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