Download Prostate cancer

Nuno Gil
XIV WORKSHOP ON ONCOLOGICAL UROLOGY
Relevance of bone metastasis
World prevalence
(5 years)
Incidence of bone
metastasis
Median survival
(months)
Multiple myeloma
144.000
70-95%
6-54
Kidney
480.000
20-25%
6
Melanoma
533.000
14-45%
6
Thyroid
475.000
60%
48
Lung
1.394.000
30-40%
6
Breast
3.860.000
65-75%
19-25
Prostate
1.555.000
65-75%
12-53
Tumor
A. Lipton, J Support Oncol 2004;2:205–220
Relevance of bone metastasis

> 500,000 patients in the United States/year

Myeloma: > 90% of patients

Breast: 2/3 of patients

Prostate: 2/3 of patients

Lung: 1/3 of patients

Often only site of metastatic disease

Prolonged survival; often measured in years

Major clinical consequences for patients, families, and society
Consequences of bone metastasis
Pathologic fractures
Nonvertebral
Vertebral compression
Spinal cord compression
Radiation therapy
Surgery to bone
Hypercalcemia
SREs
Incidence of SREs
Total SREs
Radiation
Fracture
1,2
Breast
Myeloma 3
4,5
Prostate
Lung/Other
Hypercalcemia
Surgery
5
Spinal
compression
0
10
20
30
40
50
60
70
1. Hortobagyi et al. J Clin Oncol. 1998;16:2038-2044. 2. Theriault et al. J Clin Oncol. 1999;17:846-854. 3. Berenson et al. J Clin Oncol. 1998;16:593-602.
4. Saad et al. J Natl Cancer Inst. 2002;94:1458-1468. 5. Novartis. Data on file.
Costs associated with bone mets
Cost per patient, 2004 (USD)
396,200 patients diagnosed with cancer between 2000 and 2004
56281 USD
60,000
36500
40,000
19781 USD
20,000
0
MBD
(N=519)
No MBD
(n=520)
Schulman KL, Kohles J. Economic burden of metastatic bone disease in the US. Cancer. 2007
Prostate cancer
Incidence of SREs in prostate cancer (24 months)
49%
Total SREs
50%
Pathologic fracture
30%
Radiation
33%
40%
Surgery
25%
Spinal compression
Hypercalcemia
20%
10%
4%
8%
0%
Saad F, et al. Eur Urol Suppl. 2007;6 (Issue 11):683-688.
1%
Bone mets = worse prognosis
1-year Survival
1-year adjusted
mortality rate
(95%CI)
After 1-year adjusted
mortality rate (95%CI)
19.826
(86)
87%
Reference
Reference
Bone metastasis and no
SREs
1.570
(7)
47%
4,7 times greater
6,1 times greater
Bone metastases and at
least 1 SRE
1.691
(7)
40%
6,6 times greater
9,8 times greater
N
(%)
No bone metastasis
Group
Fryzek JP, Cetin K, Nørgaard M, et al. The prognostic significance of bone metastases and skeletal-related events (SREs) in
prostate cancer survival: A population-based historical cohort study in Denmark (1999-2007). J Clin Oncol. 2009;27:15s.
Abstract and Poster 5160.
Incidence of SRE with respect to symptoms
Eastham J, McKieman J, Gleason D, Zheng M, Saad F., J Clin Oncol. 2005;23:16s. Abstract 4561 and presentation.
Major P., EU J Onc Nursing. 2007;11:S32-S37.
Costs associated with SREs
13051
cost, euros
15,000
10,000
6973
5,000
0
Cost with
SREs
Total cost treatment of
metastatic prostate cancer
Groot et al. Eur Urol. 2003;43:226-232.
Costs associated with SREs
Lage M, Am J Manag Care. 2008;14(5):317-322)
Phase III trials of bisphosphonates
Study
Population
Treatment
Endpoint
Results
NCIC Pr06
(N=204) (1)
Symptomatic
Mitoxantrone/
PDN ± clodronate
Palliative
response
OS, PFS, QoL
NS
032/INT 05
(N=350) (2)
Symptomatic
Pamidronate vs
placebo
Pain score,
analgesic use
Pain, analgesic use, SREs
NS
Asymptomatic
Zoledronic acid
vs placebo
SREs
SRE: 44 vs 33% (p=0,021)
Zoledronic acid 039
(N=643) (3)
1. Ernst DS, et al. J Clin Oncol. 2003;21:3335-3342; 2. Small EJ, et al. J Clin Oncol. 2003;21:4277-4284; 3. Saad F, et al. J Natl Cancer Inst.
2002;94:1458-1468.
Bisphosphonates – what do they do?
Patients without SRE (%)
100
Zoledronic acid 4 mg
Placebo
80
Median, days
488
321
P value
.009
60
40
167 days
20
0
0
120
Saad F. AUA 2003. Abstract 1472.
240
360
480
600
720
Days since beginning of treatment
Renal cell carcinoma
Bisphosphonates – what do they do?
Saad F, Seminars in Oncology, Vol 37, No 3, Suppl 1, June 2010, pp S38-S44
Bladder carcinoma
Bisphosphonates – what do they do?

ASCO 2008 (abst. 5033) Zaghloul et al. A controlled
prospective randomized placebo-controlled trial of
zoledronic acid in bony metastatic bladder cancer
patients. (N=40)
Median time for first SRE: 56 vs 118 days (p=0,0004)
 OS (1 year): 5 vs 30%

Bisphosphonates – what do they do?

ASCO 2010 (abst. E15096) Hoshi et al. The impact
of zoledronic acid therapy in survival of bladder
cancer patients with bone metastasis. (N=30)
OS: 17 vs 7 months (p=0,003)
 Pain score: NS

Conclusions
Bisphosphonates – what do they do?
Risk redution
P value
Breast
41%
.019
Prostate
36%
.002
Solid tumors
31%
.003
Lung
32%
.016
Kidney
58%
.010
0
0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0
SRE relative risk
ZOL better
Placebo better
Kohno N, et al. J Clin Oncol. 2005;23:3314-332. Saad F, et al. J Natl Cancer Inst. 2004;96:879-882. Rosen LS, et al. Cancer.
2004;100:2613-2621. Lipton A, et al. Cancer. 2003;98:962-969.
Zoledronic acid and SREs in GU cancers
% patients with any SRE
100
80
60
Placebo
Zoledronic acid
40
20
0
Prostate
Kidney
Bladder
John M. Fitzpatrick, European Urology Supplement S 8 (2009): 733–737
Impact of bone metastasis
Increased medical costs[1]
Treatment of bone complications more than doubles the total
treatment costs for patients with bone metastases
Impaired mobility[6]
Hip fracture
associated with a 50%
disability rate; 25% of these
require nursing home care
Skeletal
Complications
Diminished
quality of life[2-4]
History of a skeletal
complication is associated
with lower QoL in breast and
prostate cancer
Negative impact on survival[5]
Men with prostate cancer without skeletal fracture survived 39 months
longer than those with a fracture
1. Groot MT, et al. Eur Urol. 2003;43:226-232. 2. Weinfurt KP, et al. Ann Oncol. 2002;13(suppl 5):180. 3. Weinfurt KP, et al. Med Care. 2004;42:164-175. 4. Saad
F, et al. Eur Urol. 2004;46:731-740. 5. Oefelein MG, et al. J Urol. 2002;168:1005-1007. 6. Riggs BL, et al. Bone. 1995;17:505S-511S.
Bisphosphonates – don’t forget

Adjust the dose to kidney function!
Bisphosphonates – don’t forget
ONJ - prevalence
Study
Type
Pts Treated With
BP, n
Pts With Suspect or
Proven ONJ, n
Frequency, %
Chart review
4019
34
0.8
Web-based survey
1203
152
12.6
Pozzi et al, Italian Multicenter
study[3]
Chart review
888
16
1.8
Badros et al[4]
Chart review/
observational
340
11
3.2
Retrospective review of
trial database
259
6
2.7
Zervas et al[6]
Observational
254
28
11.0
Dimopoulos et al[7]
Chart review
202
15
7.4
Cafro et al[8]
Chart review
118
14
11.9
Berenson et al[9]
Chart review
300
14
4.7
Study
Hoff et al, MDACC
ASCO 2006[1]
Durie et al[2]
Tosi et al, analysis of
Bologna 2002 trial[5]
1. Hoff AO, et al. ASCO 2006. Abstract 8528. 2. Durie GM, et al. N Engl J Med. 2005;353:99-102. 3. Pozzi S, et al. ASH 2005. Abstract 5057. 4. Badros A, et al. J Clin
Oncol. 2006;24:945-952. 5. Tosi P, et al. ASH 2005. Abstract 3461. 6. Zervas K, et al. Br J Haematol. 2006;134:620-623. 7. Dimopoulos M, et al. Haematologica.
2006;91:968-971. 8. Cafro A, et al. ASH 2005. Abstract 5152. 9. Berenson J, et al. Clin Lymphoma Myeloma. 2009;9:311-315.
Bisphosphonates – don’t forget



Check the teeth of your patients BEFORE
bisphosphonates
Avoid invasive dental procedures during therapy
If you have to, STOP bisphosphonates at least for 3
months before planned dental procedure
Thank you for your attention