Latest developments in Prostate Cancer - PowerPoint PPT Presentation

View by Category
About This Presentation
Title:

Latest developments in Prostate Cancer

Description:

Latest developments. in Prostate Cancer. 7th ESMO Patient Seminar. Stockholm. 14 / 09 / 2008 ... Localized Prostate Cancer - HIFU Treatment ... – PowerPoint PPT presentation

Number of Views:922
Avg rating:3.0/5.0
Slides: 64
Provided by: europ6
Learn more at: http://www.europauomo.sk
Category:

less

Write a Comment
User Comments (0)
Transcript and Presenter's Notes

Title: Latest developments in Prostate Cancer


1
Latest developments in Prostate Cancer
  • 7th ESMO Patient Seminar
  • Stockholm
  • 14 / 09 / 2008

Hein Van Poppel Chair Sc.Comm.

Leuven, Belgium
2
Relative Survival () during
Source SEER Program,
1975-2000, NCI, 2003.
1974-1976
1983-1985
1992-1999
Site
   
  • Breast (female) 75 78 87
  • Colon rectum 50 57 62
  • Leukemia 34 41 46
  • Lung bronchus 12 14 15
  • Melanoma 80 85 90
  • Non-Hodgkin lymphoma 47 54 56
  • Ovary 37 41 53
  • Pancreas 3 3 4
  • Prostate 67 75 98
  • Urinary bladder 73 78 82

3
1. SCREENING andEARLY DETECTION
4
Anything next to PSA?
  • PCA3
  • EPCA

5
A New Test on the Horizon
  • PCA3DD3 is the most prostate-cancer-specific gene
    described to date
  • Over-expressed in gt95 of PC
  • Expression restricted to the prostate

6
ButHow reliable is the 35 cut-off ?
7
The EPCA Test
8
EPCA A PrCa revolution
  • Early Prostate Cancer Antigen - 2

  • Dr.Getzenberg et al., J.Urol.2007
  • Structural protein in the nucleus of Pr Ca cells
    Function?
  • False Positive 3...had no cancer
  • False Negative 6...had cancer
  • Separates Prostatitis , BPH
  • Identifies -more or less aggressive cancers
  • -localized and locallly advanced Ca

9
PSA remains keyPCA3 and other markers help in
counseling, deciding on biopsy, repeat biopsy,
and also on management
10
Urine Biomarkers
  • Expression of Prostate specific genes
  • - TMPRSS2 ERG fusion status
  • - GOLPH2, SPINK1, PCA3 expression
  • all significant predictors of PrCa
  • Combination PCA3 TMPRSS2 ERG expression in
    urine is better than PSA and PCA3
  • Chinnaiyan, Cancer Res. 2008

11
Other genetic markers
  • In PrCa gene fusions involving oncogenic ETS
    transcription factors like ERG, ETV1 and ETV4
    have been identified
  • Most common fusion TMPRSS2 fused to ERG
  • Fusion to ETV1 TMPRSS2, SLC45A3,
    HERV-K_22911.23, C150RF21, HNRPA2B1
  • ETV5 (new oncogene ETS transciption factor)
    TMPRSS2, SLC45A3
  • Helgeson, Cancer Res. 2008

12
Other genetic markers
  • Gene MSMB and LMTK2 in blood
  • ? genetic profiling can be offered to men to
    assess the risk of developing PrCa
  • Ros Eeles, Nature Genetics 2008

13
2. PREVENTION
14
Widespread use of finasteride cost-effective?
  • Finasteride is unlikely to be cost-effective when
    considering the impact on survival differences
  • Maybe cost-effective in high-risk population
  • Svatek et al., Cancer 2008

15
Recent Literature on Chemoprevention
16
Chemoprevention
  • PCPT - finasteride reduces PrCa prevalence
  • - decreases PIN
  • PLCO - vegetable intake decreases ECE
  • - spinach,brocoli,cauliflower
  • Physicians Health Study -Vit.D
  • - marine source fatty acids
  • Soy, Vit E and Se suppl. decreases HGPIN


I.Thompson,JUrol 07
V.Kirsh,JNCI 07
H.Li et al., NCPU 07
Chavarro, CEBP 07
S.Joniau, Urology 07
17
Cholesterol lowering drugs decrease the risk of
PrCa in a dose dependent matter
Atorvastatin, Lovastatin, Simvastatin
Murtola, UroToday, 2008 Genistein decreased
metastasis from PrCa by 96 in mice without
effect on the primary R. C. Bergen, Cancer
Res. 2008
18
3. BONE STAGING
19
Place of MRI in Bone Staging
  • Bone scan still standard diagnostic tool
  • - if normal OK, no MRI
  • - if abnormal - X-ray normal ? MRI
  • - X-ray explains
    bone scan ? no MRI
  • Venkitaraman, JCO 2007

20
4. MANAGEMENT
21
  • 1. Radical Prostatectomy
  • 2. Active Surveillance
  • 3. Radiotherapy Brachy
  • 4. HIFU and Cryo
  • 5. Focal therapies
  • 6. Medical treatments

22
Primary Treatment according to Specialist Consult
(N-85.088)
Specialty RPr XRT Hormones A.S.
Urology (N 42,309) Urology (N 42,309) Urology (N 42,309) Urology (N 42,309) Urology (N 42,309)
65-69 (N 12,248) 70 5 7 18
70-74 (N 10,751) 40 8 17 31
75 (N 19,310) 5 4 45 46
Medical Oncology (N 2,329) Medical Oncology (N 2,329) Medical Oncology (N 2,329) Medical Oncology (N 2,329) Medical Oncology (N 2,329)
65-69 (N 601) 53 17 14 16
70-74 (N 657) 38 22 17 23
75 (N 1,071) 5 15 46 34
T. Jang, NCI, 2007
23
Primary Treatment according to Specialist Consult
(N-85.088)
Specialty RPr XRT Hormones A.S.
Radiation Oncology (N 37,540) Radiation Oncology (N 37,540) Radiation Oncology (N 37,540) Radiation Oncology (N 37,540) Radiation Oncology (N 37,540)
65-69 (N 10,604) 15 78 3 4
70-74 (N 14,058) 7 85 4 4
75 (N 12,878) 2 85 7 6
Radiation Medical Oncology (N 2,910) Radiation Medical Oncology (N 2,910) Radiation Medical Oncology (N 2,910) Radiation Medical Oncology (N 2,910) Radiation Medical Oncology (N 2,910)
65-69 (N 890) 19 70 6 5
70-74 (N 1,037) 8 80 7 5
75 (N 983) 2 79 12 7
T. Jang, NCI, 2007
24
1. RADICAL PROSTATECTOMY
25
SURGICAL QUALITY of RPr
  • Not only laparoscopic radical prostatectomy but
    also open surgery is not always well performed
  • Experts in both techniques will have better
    results, novices and ill trained or unskilled
    surgeons will perform
  • poorly with both approaches

26
Radical Prostatectomy (RPr)
  • Nerve sparing RPr improves continence rates
  • Nandipati et al., Urology 2007
  • Laparoscopic RPr can give rise to port site
    metastasis
    Savage
    et al., Urology 2007
  • Robot versus open health related outcomes are
    equal
  • - 117 Robot vs. 89 open RPr,
    self-administered

    questionnaire
  • - Robot less narcotics (32 mg versus 52 mg)
  • shorter hospitalisation (1,2
    versus 1,3 days)
  • equal time back to normal
    activity
  • D.P. Wood et al., Urology 2007

27
What about the Robot?
  • Pain
  • Recovery
  • Early Continence
  • Early Potency

28
RPr in very high risk disease
Experience with RRP for PSA gt100 26 pts, with
median fu of 66.5 months (range 12-158)
Median PSA (range) 139.7 ng/ml (100-630)
pT2 2/26 (7.7)
pT3a 7/26 (26.9)
pT3b 7/26 (26.9)
pT4 10/26 (38.5)
N 12/26 (46.1)
SM pos 22/26 (84.6)
Median final GS (range) 8 (6-10)
Adjuvant/Salvage RT or HoT 24/26 (92.3)
10-year BPFS 11.3
10-year CPFS 47.5
10-year CSS 88.7
10-year OS 54.1
J oniau, Gontero and Van Poppel, data on file
29
Multimodal treatment of life-threatening cancers
Radical Prostatectomy followed by
adjuvant / salvage radiation or hormone
treatment
30
2. SURVEILLANCEACTIVE MONITORING- WATCHFUL
WAITING

31
PRIAS trial Inclusion
  • PSA below 10 ng/ml
  • PSA density below 0.2
  • Gleason score 6 or less
  • Sufficient number of biopsies
  • No more than 2 cores invaded
  • Clinical T1-T2
  • Fit for curative treatment
  • but willing to attend follow-up

32
PRIAS trial Follow-up
  • PSA check / 3mos for 2 years, if stable / 6mos
  • DRE every 6 months
  • PSA kinetics (velocity and doubling time)
  • Repeat PPB at 1, 4, 7, and 10 years

33
ACTIVE SURVEILLANCE ?
  • Treatment decisions are influenced by anxiety,
    more than on disease progression
  • Delay of treatment can prevent some pts with
    favorable PrCa from getting effective,
    low-morbidity treatment
  • Repeat Biopsy integral part since 20-30 will
    have grade progression
  • After a mean follow-up of 4y, 1/3 pts
  • was treated (Sweden)

Latini, JUrol,07
Loeb, NCPU,07
Venkitaraman,JUrol,07
Stattin, NCPU,07
34
3. RADIOTHERAPY
35
RADIOTHERAPY
  • External Beam EBRT
  • -Modern techniques
  • -Dose escalation
  • -Comparison Rad.Prost.
  • 2. Brachytherapy

36
Treatment Trends in the US
  • 2005
  • Surgery 33
  • External 31
  • Brachy. 36
  • 1990
  • Surgery 65
  • External 30
  • Brachy. 5

37
RT Dose escalation trials
MD Anderson 305 Reported 70 vs 78 Gy
ICR/RMT 126 Reported 64 vs 74 Gy (LHRH)
Mass/Loma Linda 393 Reported 70.2 vs 79.2 Gy
Dutch trial 664 Reported 68 vs 78 Gy ( LHRH)
MRC RT01 850 Completed 64 vs 74 Gy (LHRH)
FNC LCC 300 Completed 70 vs 78 Gy
RTOG 1520 Ongoing 72 vs 78 Gy
38
Dutch Multicentre trial late side effects
  • RTOG Grade 2
  • GI 27 vs 32 (p0.2)
  • GU 39 vs 41 (p0.6)
  • BUT
  • Rectal bleeding 4 vs 9 (p0.02)
  • Incontinence pads 7 vs 12 (p0.03)

N.S. ?
39
Can one compare RPr versus RT ?
40
15y OS RPr vs RT vs WW
RPr
RT
Obs.
Connecticut Tumor Registry 1618 pts, 1990-1992
P.Albertsen et al.,J.Urol. 2007
41
Treatment Trends in the US
  • 2005
  • Surgery 33
  • External 31
  • Brachy. 36
  • 1990
  • Surgery 65
  • External 30
  • Brachy. 5

42
BrachytherapyBiochemical Control - 10 Years
  • 125 patients diagnosed 1988 - 1990
  • Stage T1 - T2b, Gleason lt 6
  • Biochemical control -10 years 85,1 (ASTRO
    criteria)
  • Control based on PSA at diagnosis
  • PSA initial 0-4 4-10 10-20 gt20
  • n 54 42 19 9
  • bNED 96 76 58 46

Grimm, IJROBP, 51 31, 2001
43
Clinical Results (bNED)
ERT
Brachy
Seattle
RPr
Low risk 93 85 85 94 Intermediate risk
66 64 35 74 High risk 40 38 10 50
DAmico et al, JAMA, 1998
44
Brachytherapy Update Literature
  • 308 Brachy vs 127 RPr multicenter France
  • Whereas RPr gives a very marked impairment in
    Health related QoL immediately after treatment
    with subsequent improvement, brachytherapy shows
    a moderate but persistent impairment in QoL over
    2 years

Buron et al., IJROBP, 2007
45
Place of Brachytherapy in 2007
  • Excellent results in well selected patients
  • Excellent results in centers of excellence
  • Best results in those that do not need any
    treatment
  • Value as alternative to RPr in younger patients ?

46
4. HIFU - Cryo
47
Localized Prostate Cancer- HIFU Treatment -
  • Salvage therapy for local relapse after EBRT
    failure
  • A last opportunity??

48
CRYOTHERAPY
  • LUTS settle down with time ..
  • Long-term PSA results awaited ..
  • Ongoing E.D. still a problem (?)

49
CRYOSURGERY Salvage Treatment
Biochemical NED 40 - 70 after 12 - 50 months
COMPLICATIONS Incontinence
10-80 Impotence
72-100 Retention/Stricture
10-55 Pelvic pain
6-77 Recto-urethral fistula
0-11
N.Touma. J.Urol. 2005 173373-379
50
Summary
  • Brachytherapy low risk patients
  • HIFU Salvage therapy
  • Cryotherapy Experimental !

51
5. MEDICAL TREATMENTS
52
Castration
53
Androgen deprivation therapiesSide effects
  • Frailty accelerated increased risk for falls,
    hospitalisation and death
  • Bylow et al., Cancer 2007
  • Diabetes Negative effect on glycaemia control
    and aggravation of risk profile
  • Haidar et al., Aging Male 2007
  • M. Lage et al., Urology 2007
  • . Cardio-vascular death 1.2 2x increased
    risk
  • (even short
    time ADT)

Tsai et al., JNCI 2007 Saigal et al., Cancer 2007
54
LHRH Antagonists
55
A new class GnRH blockers
  • The blockade immediately reduces the production
    of testosterone by the testicles
  • No testosterone increase as with LHRH-a
  • Degarelix has a fast, profound and sustained
    suppression of testosterone and PSA, without
  • testosterone surge or clinical flare

56
HRPC
57
Referral of PrCa pts for Chemo
  • Since ASCO 2004, referrals by US urologists to
    oncologists have increased

lt50 increase in number of patients treated per
month!
ASCO 2004
58
HRPC
  • Abiraterone acetate
  • - Irreversible inhibitor of CYP17
  • - Decreases T and DHT to undetectable levels
  • - After Taxotere failure, 1g PO/day
  • Prednisone 5 mg/day
  • - 44 PSA decline gt 50
  • - Some had unchanged bone scan
  • - Phase III trial planned
  • Daniela et al., ASCO 2008

59
HRPC
  • Sorafenib
  • - Phase II HRPC, 2 x 400 mg/day orally
  • - Gleason 9 , PSA 2 1905
  • - 22 patients
  • - well tolerated, how to follow ? PSA no
  • Lesions no
  • ??
  • Dahut et al., Clin Cancer Res 2008

60
HRPC at SUO 2008 by Dan Petrylak
  • Satraplatin (SPARC) No overall survival
    benefit
  • Taxotere (SWOG-TAX 327) 3 mo survival
    difference
  • Sipuleucel immunomodulator
  • 33 survival
    (placebo 15 )
  • GVAX 7 13 months survival benefit
  • ZD4054 Phase II superior to placebo (phase III
    ongoing)
  • Calcitriol Taxotere (ASCENT) more deaths!
  • Bevacizumab Taxotere is studied
  • Atrasentan Taxotere is studied

61
EAU topics 2008
Urology Week 15-19 sept 2008
62
Conclusion IWhat is new in Prostate Cancer?
  • PSA is useful for screening, new genetic tests
    emerge and PCA3 can be helpful
  • Prevention finasteride in high risk men, diet..
  • MRI is helpful for bone evaluation
  • Urologist do more surveillance than RT or MO
  • Surgery has the best results if treatment is
    needed superiority of Robot?
  • High risk patients can benefit from
  • starting with surgery

63
Conclusion IIWhat is new in Prostate Cancer?
  • Radiotherapy continues to improve but is not
    optimal in young patients dose escalation !
  • Brachy cures cancers that might just be followed,
    HIFU salvages RT failures
  • Androgen deprivation induces frailty, diabetes
    and increases CV mortality
  • HRPC remains the challenge, and new (vaccination
    ?) strategies need to be
  • further explored
About PowerShow.com