Prostate Cancer - PowerPoint PPT Presentation

1 / 59
About This Presentation
Title:

Prostate Cancer

Description:

Prostate Cancer Mr R Puri BSc, MBBS, MS, D Urol, FRCS(Urol) Consultant Urologist Bradford Royal Infirmary Relationship of the prostate to the urogenital tract What ... – PowerPoint PPT presentation

Number of Views:1218
Avg rating:3.0/5.0
Slides: 60
Provided by: Dr1024
Category:

less

Transcript and Presenter's Notes

Title: Prostate Cancer


1
Prostate Cancer
  • Mr R Puri
  • BSc, MBBS, MS, D Urol, FRCS(Urol)
  • Consultant Urologist
  • Bradford Royal Infirmary

2
Relationship of the prostate to the urogenital
tract
3
(No Transcript)
4
What does the prostate do?
  • The coagulum formed by the ejaculated semen
    liquefies within 20 minutes as a result of
    prostate proteolytic enzymes
  • Best known is Prostate Specific Antigen
  • PSA

5
What does the prostate do?
  • Contributes to the seminal plasma
  • 60 seminal vesicles
  • 20 prostate
  • Prostate add
  • PSA
  • Zinc
  • Phospholipids
  • Spermine

6
Age-adjusted incidence and mortality rates in the
UK and the USA
Oliver et al 2000
7
Prostate CancerFacts
  • Commonest cancer in men after middle age
  • Second only to lung cancer as cause of death in
    men
  • Histological prostate cancer in 30 of population
  • Lifetime risk of developing clinical prostate
    cancer is 10
  • Risk of death from prostate cancer is 3

8
NYCRIS Data 1998Bradford HA pop. 483285
  • Incidence - Europe
  • Mortality - Europe
  • Incidence - NYCRIS
  • Mortality - NYCRIS
  • - 65.1/100,000
  • - 25.2/100,000
  • - 76.4
  • - 30.5

9
Bradford HA pop. 483285Extent of problem
  • New cases per year - 183
  • Deaths due to Ca P - 73
  • Only 94 out of the 183 will be offered
    potentially curative treatment

10
Detection of Prostate Cancer
  • Digital Rectal examination
  • PSA testing
  • Trans rectal ultrasound and biopsy

11
PSA production and action
Epithelial cell
Nucleus
PSA secretedinto gland lumen and blood stream
DHT
PSA(neutral serine protease)
Testosterone
5a-R
Translation
Transcription
mRNA
T, testosterone DHT, dihydrotestosterone 5a-R,
5a-reductase
http//www.uronet.org/visual/mar97/image4.gif
12
PSA values
  • Age specific
  • 40 - 49 2.5 ng/ml (ug/L)
  • 50 - 59 3.5
  • 60 69 4.0
  • 70 79 6.5
  • ERSPC - any value above 3 is abnormal
  • Recent US guidelines - any value above 2.5 is
    abnormal

13
PSA values-2
  • PSA 2.5 4 12 CaP
  • 4 - 10 36 CaP
  • gt 10 50 CaP
  • Free / Total PSA
  • Complexed PSA
  • PSA density
  • PSA velocity

14
PresentationLocalised Disease
  • Local Disease
  • Asymptomatic
  • Raised PSA
  • LUTS
  • Obstructive
  • Irritative
  • UTI
  • Locally Advanced
  • Haematuria
  • Impotence
  • Suprapubic and perineal pain
  • Haemospermia
  • Anuria
  • Renal failure

15
PresentationMetastatic Disease
  • Low back pain
  • Spinal cord compression
  • Bone pain
  • Anaemia
  • Weight loss

16
Presentation
  • Why wait for symptoms ?
  • Or
  • Should we screen for prostate cancer ?

17
Does screening decrease prostate cancer death?
Bartsch et al 2000Gohagan et al 1994 Labrie et
al 1999 Schröder et al 1999
18
Benefits of PSA/DRE Screening European
Experience
  • County Tyrol, Austria
  • Population 630,000
  • Free PSA testing available 24hrs a day since 1993
  • Decrease in mortality due to CaP by 32,42 ,33
    in 1997,98 99
  • Stage migration - Organ confined cancers
    increased from 28 in 93 to 82 in 98

19
Early Detection of Prostate CancerAre There Any
Benefits?
  • In non screened populations only 30 of CaP
    detected is organ confined
  • Only 22 of patients with PSA gt10 have organ
    confined disease
  • Only 30 of patients with T3 disease are free of
    PSA recurrence 5 years after Radical
    Prostatectomy

20
Early Detection of Prostate CancerAre There Any
Benefits?
  • In screened population 71-97 of the detected
    cancers were organ confined at staging
  • 70 of these cancers are organ confined after
    radical prostatectomy
  • 10 year PSA non progression rate is 80
  • Disease specific survival rate at 15 years is
    84-97

21
Screening for prostate cancerconclusions
  • Ongoing debate would increased detection
    decrease disease-specific mortality?
  • Screening costs need to be balanced against
    higher costs of treating patients with advanced
    disease
  • Costs could be considerably reduced by increased
    sensitivity of screening assay

22
Diagnosistransrectal ultrasound (TRUS)
http//www.uronet.org/visual/jan96/image6.jpg
23
Biopsy technique
24
Histological gradingGleason system
Kirby 1999
25
Why the Debate About Treating Prostate Cancer?
  • Prostate cancer is unique amongst solid tumours
    in that it exists in two form
  • Pussy cat
  • Tiger

26
Why the Debate About Treating Prostate Cancer?
  • Latent Cancer (Pussy Cats)
  • Prevalence 20-48, increases with age
  • 60 -70 of men over 80 years have latent
    carcinoma prostate
  • Well to moderately differentiated, localised, CaP
    in older men is often not clinically significant

27
(No Transcript)
28
Why the Debate About Treating Prostate Cancer?
The Tigers
  • A patient below 65yrs diagnosed to have a CaP has
    a75 chance of developing metastasis and 52
    chance of dying from CaP if he lives 15 years
  • Screening does not detect latent cancer
  • Majority of cancers detected on screening are
    localised cancers
  • Localised CaP is curable

29
Treatment for prostate cancer
Localisedprostatecancer
Metastatic disease
Hormone insensitive
Locallyadvanced
High-grade PIN
D1.5
D2
D2.5
D3
TxN0M0
T3-4
Time (years)
Treatment options
Radical prostatectomy Radiotherapy Watchful
waiting
Hormonal therapy
Chemotherapy
Radiotherapy Hormonal therapy Watchful waiting
PIN, prostatic intraepithelial neoplasia
30
Clinical staging TNM 1997
T1a/b T1c T2a T2b
T3a T3b T3c T4
T1a
T1b
T1c
31
Clinical staging (4)
N
Nx loco-regional lymph nodes cannot be
evaluatedN0 no lymph node involvementN1-N3
regional lymph metastasis N1 solitary lt2 cm N2
solitary gt2 cm and lt5 cm N3 gt5 cm
D1-D1.5
M
Mx no metastasis can be evaluatedM0 no
distant metastasisM1 distant metastasis
present a lymph nodes other than
regional nodes b skeletal c other sites
D2-D2.5
D3S hormone sensitive D3I hormone insensitive
No TNM equivalent
32
The use of nomograms for predicting disease
recurrence
  • Preoperative PSA level
  • Preoperative Gleason score
  • TNM clinical stage

Preoperative and postoperative nomograms
Kattan et al 1998 Kattan et al 1999 Partin et al
1997
33
Partins NormogramsT1c (inpalpable) Gleason sum
score 7
  • PSA lt4
  • OC 63
  • PSA 4-10
  • OC 49
  • PSA 10 20
  • OC 35
  • T2a
  • OC 22

34
TreatmentLocalised Prostate Cancer
  • Radical Prostatectomy
  • Retropubic
  • Perineal
  • Laproscopic
  • Robotic
  • Radiotherapy
  • External beam CT guided Conformal
  • Brachytherapy
  • Experimental
  • Cryotherapy

35
Radical Prostatectomy
36
(No Transcript)
37
Disadvantages of Radical Prostatectomy
  • Mortality 0.5
  • Incontinence rate 10
  • Impotence gt50
  • ? Effect on survival
  • Majority of patients would be happy to go through
    the procedure again inspite of the side effects

38
Radiotherapy
Brachtherapy
External Beam RT
  • Standard
  • Conformal CT guided planning
  • Iodine
  • Palladium

TRUS planning MRI planning
Adjuvant Hormone Treatment Neoadjuvant Hormone
Treatment
39
BrachytherapyTransperineal seed implant
Belldegrun et al 2000
40
Brachytherapy vs radical prostatectomy7-year
progression-free survival
Brachytherapy 79 79
Radical prostatectomy 84 98
No. patients 299 198
Ramos et al 1999 Polascik et al 1998Ragde et
al 1997
41
Radiotherapy plus hormonal therapy for locally
advanced prostate cancer
Neoadjuvant Pilepich et al 1995RTOG
86-10 Shearer et al 1992 Adjuvant Bolla et al
1997, 1999EORTC 22863 Pilepich et al
1997Lawton et al 1999RTOG 85-31 Granfors et al
1998
Significant improvement in progression-free
survival Significant reduction in tumour volume
(downsizing) Significant improvement in overall
survival disease-free survival Significant
improvement in overall 5-year survival (for poor
prognosis patients) Significant improvement in
progression-free survival overall survival
42
Management of locally advanced/ metastatic
prostate cancer
  • LHRH agonists
  • Orchiectomy
  • Antiandrogen monotherapy
  • Maximal androgen blockade

43
Early treatment of locally advanced
disease/metastatic/poorly differentiated cancer
  • Treatment of T3NXM0
  • MRC study Feb 1997 BJU
  • Deferred treatment resulted in
  • Higher incidence of local progression
  • Higher incidence of painful metastasis
  • Higher incidence of ureteric obstruction
  • Twice the number of serious complications
  • Disadvantage in terms of survival

44
Prostate cancer is hormone-dependent
Testosterone
Testes
Pituitary
Hypothalamus
Prostate
Oestrogen
LH
Prolactin
LHRH
ACTH
Adrenal
Cortisol
Adrenalandrogens
LHRH, luteinising hormone-releasing hormone LH,
luteinising hormoneACTH, adrenocorticotrophin
45
LHRH Agonists
  • Zoladex
  • Prostap

46
Mechanism of action of Zoladex (goserelin)
Furr and Hutchinson 1992
47
Administration of Zoladex (goserelin)
48
Antiandrogens chemical structures
CH3
NHCOCOH
NO2
CH3
CF3
Hydroxyflutamide
Casodex (bicalutamide)
CH3
C O
CH3
CH3
CH2
O
CI
Nilutamide (RU 23908)
Cyproterone acetate
49
Mechanism of action of Flutamide Casodex
(bicalutamide)
Androgens
ACTH
Prostate cell
Adrenal gland
Nucleus
DHT
LHRH
X
Hypothalamus
Other target tissues
Pituitary gland
Casodex (bicalutamide)
DHT
Androgen receptor
Testis
LH
Circulating testosterone
-ve feedback control
50
Overall survival in M0 patients median 6.3
years follow-up
patients surviving
100
80
60
40
Casodex (bicalutamide) 150 mg
20
Castration
0
0
200
400
600
800
1000
1200
1400
1600
1800
2000
2200
2400
2600
2800
Time (days)
Iversen et al 2000
HR 1.05 95 CI 0.81, 1.31 p0.70
51
Hormone insensitive prostate cancerOptions
  • Antiandrogen withdrawal
  • Second-line hormonal therapy
  • Chemotherapy

52
Role of androgen ablation in hormone
sensitive/insensitive prostate cancer
  • Not all of the cancer will be unresponsive and
    discontinuation of androgen suppression could
    allow tumour regrowth
  • Continued androgen suppression may provide
    survival benefits in hormone-refractory prostate
    cancer
  • Androgen ablation should be continued
    indefinitely based on minimal risk versus
    potential benefits

53
The role of antiandrogens in hormone
insensitive prostate cancer
  • Progressing prostate cancer may respond to
    switching the antiandrogen therapy
  • Casodex (bicalutamide) is effective in some
    patients previously treated with flutamide
  • flutamide is effective in some patients in whom
    first-line hormonal therapy has been highly
    effective
  • There are treatment options if patients progress
    on antiandrogens
  • Stilboesterol
  • Honvan

54
Chemotherapy
  • In patients with hormone-refractory prostate
    cancer
  • prednisone
  • mitoxantrone
  • docetaxel
  • estramustine
  • ZD1389

55
ZD1839 mechanism of actionPotent and selective
inhibitor of the epidermal growth factor receptor
(EGFR)
EGF
TGFa
Membrane
Cancer cell
X
Kinase
Nucleus
56
HOLISTIC APPROACH
  • It is the recognition that the patient must be
    educated so that he can, understand how to live,
    and sometimes die with his disease,
  • but without anxiety.

57
Case 1
  • 62 year civil servant presents with
  • nocturnal voiding frequency of times for last 6
    months

58
Case 2
  • 72 years old farmer presents with haemospermia.
    PSA 17 clinically T2b neoplastic prostate

59
Case 3
  • 79 years old with acute retention
Write a Comment
User Comments (0)
About PowerShow.com