ca prostat jogya mei 2010
TRANSCRIPT
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Manajemen Kanker Manajemen Kanker ProstatProstat
dan Kanker Buli-dan Kanker Buli-BuliBuli
Rainy UmbasRainy UmbasDepartemen UrologiDepartemen UrologiRumah Sakit Cipto Rumah Sakit Cipto Mangunkusumo Mangunkusumo
Universitas IndonesiaUniversitas Indonesia
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Presentasi Penderita Keganasan UrologiPresentasi Penderita Keganasan UrologiRSCM & RSKD 1995-2009, n= 2001RSCM & RSKD 1995-2009, n= 2001
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2734 36
41
52 54
67 70
8075
8389
2129
49
30
4048 50
43
53 55
39 38
24
23 27
42
28
21
0
20
40
60
80
100
1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009
Prostate Cancer Bladder Cancer
Prostate cancer patients (1995-2009), n=782 Bladder cancer patients (1995-2009), n=586
Div. of Urology, Dept. of Surgery / “Cipto Mangunkusumo Hosp”& “Dharmais” National Cancer Center
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GAMBARAN KLINIK DAN GAMBARAN KLINIK DAN PENANGANAN KANKER PENANGANAN KANKER
PROSTATPROSTAT
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Prostate: Small gland ..... Big Prostate: Small gland ..... Big problemproblem
Prostatitis
BPH
Prostate cancer
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41
54
8983
27
7580
6770
52
3634272324
0102030405060708090
100
1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009
Prostate cancer patients (1995-2009)Div. of Urology, Dept. of Surgery / “Cipto Mangunkusumo Hospital”
& “Dharmais” National Cancer Centern= 782
• Globocan 2002: 7/100.000 ASR
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Manifestasi klinis (1)Manifestasi klinis (1)
• Tanpa keluhan (dicurigai pada pemeriksaan check up tahunan, screening, atau ada keluarga yang menderita kanker prostat)
• LUTS / retensi urin• Hemospermia• Hematuri• Nyeri tulang / fraktur patologis• Gangguan neurologis
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Manifestasi klinis (2)Manifestasi klinis (2)
• Kelainan prostat pada pemeriksaan colok dubur:- konsistensi keras- berbenjol-benjol- nodul- tidak simetri
• Kelainan prostat pada pemeriksaan trans-rectal ultra sonography (TRUS):- Lesi hypo echoic atau hyper echoic- Hypervascularisasi (Doppler)
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Manifestasi klinis (3)Manifestasi klinis (3)Penanda tumor
• Prostate specific antigen (PSA)- cut off level untuk indikasi biopsi: > 4 ng/ml- indikasi biopsi ulang dapat digunakan PSA density (PSAD), free/total PSA (f/t PSA), atau PSA velocity (PSAv)- untuk follow up hasil pengobatan
• PCA3 : pemeriksaan urin setelah dilakukan masase prostat
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Trans rectal ultra-sonography (TRUS):Trans rectal ultra-sonography (TRUS):
Dilakukan untuk mengukur volume prostat.• Bila akan memberikan pengobatan dengan 5
alpha reductase inhibitor.• Sebelum tindakan operasi atau termoterapi
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Trans rectal ultra-sonography (TRUS) & Trans rectal ultra-sonography (TRUS) & biopsi:biopsi:
Indikasi biopsi prostat:
• Kelainan pada colok dubur
• PSA > 4 ng/mlAnestesi lokal atau regional/umum
Hasil pemeriksaan histopatologi:• Jenis & grade tumor (Gleason score)• Persentase pada setiap “core”
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Derajat keganasan (grade)Derajat keganasan (grade)Diagnosis pasti kanker prostat berdasarkan
pemeriksaan histopatologi jaringan biopsi atau reseksi prostat.
Ditentukan jenis tumor dan dibuat klasifikasi derajat sesuai dengan:
• WHO : berdasarkan derajat diferensiasi yaitu baik, sedang, dan buruk (Mostofi)
• Sistem Gleason : berdasarkan pola arsitektur (morfologik) kelenjar prostat yang dibagi antara 1-5. Ditentukan dua kelompok yang paling menonjol dan dijumlah menjadi Gleason score (2-10).
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Gleason pathologic grading systemGleason pathologic grading system
Gleason DF. In: Tannenbaum M, ed. Urologic Pathology: The Prostate.Philadelphia, Pa: Lea & Febiger; 1977: 171–197
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Pain during prostate biopsyPain during prostate biopsy
How to reduced / avoid:
• Good explanation to reduced anxiety• Treat the inducing factors (prostatitis, ano-
rectal pathology)• Using analgesia in certain condition:
- very anxiety patient- biopsy > 6 core- repeat biopsy
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Pain during prostate biopsyPain during prostate biopsyDouble blinded study comparing periprostatic
injection of 1% lidocaine VS Placebo• Degree of pain was scored by VAS, 0-10.• 2.5 mL periprostatic injection around the seminal
vesicel on each side was done with 22 G needle• 18 G needle, 6-12 core.
• No significant difference of complications among these two groups.(Alvarino M & Umbas R, Indon Med J 2005)
n VAS pPlacebo
1% lidocaine
30
30
5.7 ± 1.7
2.1 ± 1.3
< 0.005
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Peri-prostatic injectionPeri-prostatic injection
Jones JS et al. Prostate Cancer and Prostatic Diseases (2003) 6, 53–55
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Tingkat penyakit (stage)Tingkat penyakit (stage)Berdasarkan sistem TNM (AJCC 2002) yang
ditentukan secara klinis (pemeriksaan fisik dan radio-imajing) atau surgical staging pasca radikal prostatektomi
• T : klinis biasanya dapat ditentukan berdasarkan karakteristik prostat pada pemeriksaan colok dubur. Cara lain adalah dengan bantuan trans-rectal ultrasonography (TRUS) atau MRI
• N : Hanya akurat dengan cara deseksi kelenjar getah bening.
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Tingkat penyakit (stage)Tingkat penyakit (stage)• M : Bone scan, MRI, Bone survey
• Surgical staging (pT & pN) berdasarkan pemeriksaan histopatologi terhadap jaringan pasca radikal prostatektomi dan/atau deseksi kgb
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Early stage Prostate CancerEarly stage Prostate Cancer
Treatment option for organ confined prostate cancer (T1a-T2b, N0, M0)
• Active surveilance / Watchful Waiting (WW)• Radical prostatectomy• Radiotherapy (EBRT or Brachytherapy)• Primary Androgen deprivation therapy
(PADT)Depend on:
risk stratification, co-morbidity, performance status, & patient preference
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Early stage Prostate CancerEarly stage Prostate Cancer
Aim of treatment:
• Cancer Control• Maintaining urinary control
(continence)• Recovery of sexual function (potency)
“ TRIFECTA “
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TREATMENT OPTIONS EAU 2008TREATMENT OPTIONS EAU 2008
LOCALIZED (grade A recommendation):• T1b – 2b, N0, M0
– Radical prostatectomy– Radiotherapy + Adjuvant Hormonal
treatment (2-3 years)
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Radical ProstatectomyRadical Prostatectomy
Is this the best
modality ?
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Radical prostatectomy: Long term Radical prostatectomy: Long term resultsresults
Cancer spesific survival (CSS): n Age group Risk group 10 years
CSS5509 < 55 years Low 99%
Medium 96%High 91%
> 70 years Low 99%Medium 97%
High 94%(Siddiqui SA et al, J Urol 2006)
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Radical prostatectomy: Long term Radical prostatectomy: Long term resultsresults
Cancer spesific survival (CSS): stage & GS
(Bianco FJ Jr et al, Urology 2005)
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Radical prostatectomy: Adverse eventsRadical prostatectomy: Adverse eventsShort term: • Peri-operative morbidity : 1.7-28.6%• Peri-operative mortality : 0.01-0.5%(Rabbani F, 2010; Mitchell RE, 2009; Chin JL, 2010)
Long term:• Urinary leakage (incontinence) : 7-
35%• Erectile dysfunction : 23-42%• Bowel urgency : 1%
(Wilt TJ, 2008; Loughlin KR, 2010; Tal R, 2009)
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Role of EBRT in early stage Prostate Role of EBRT in early stage Prostate CancerCancer• As primary treatment in pts with life
expectancy between 5-10 years or ≥ 10 years with comorbidity
• 5-years recurrence free survival : 79-91%• 5-years survival: 62-88% depend on dose, fractination, technique, and adjuvant ADT
Adverse events:- Bowel dysfunction : 9-26%- Urinary tract dysfunction : 24-28%- Erectile dysfunction : 43%
(Michalski JM, 2010; Wilt TJ, 2008)
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PADT in early stage Prostate CancerPADT in early stage Prostate CancerAs primary treatment:• Advanced age• Patient refusing curative treatment• Patient unsuitable for curative treatment
due to co-morbidity(Bartsch G et al, 6th International Consultation on new
developments in prostate cancer and prostate disease 2006)
- Could be given immediately or deferred- Continuos or intermittent
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Role of PADT in early stage Prostate Role of PADT in early stage Prostate CancerCancerManagement of localized prostate cancer (by order
of preference)(Bartsch G et al, 6th International Consultation on new
developments in prostate cancer and prostate disease 2006)
Risk Life expectancy< 5 years 5-10 years > 10 years
High:• T2b, 3a, 3b or• GS ≥ 4+3 = 7 or• PSA 10-20 or• Biopsy findings >50%, perineural, ductal
1. Hormonal Tx2. RT + HT3. Investigatio
nal therapy
1. RT + HT2. Hormonal Tx3. RP4. Investigatio
nal therapy
1. RT + HT2. RP3. Investigatio
nal therapy4. Hormonal Tx
As first preference
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Role of PADT in early stage Prostate Role of PADT in early stage Prostate CancerCancerAs primary treatment:• non-statistically significant benefit
in localized PCa pts with poorly differentiated tumor (Lu-Yao GL et al, JAMA 2008)
• No benefit and possibly greater mortality in well- or moderately differentiated stage 2 disease (Wong Y-N et al, Eur Urol 2009)
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543210
Follow Up (year)
100
80
60
40
20
0
ADT
EBRT
Figure 2: 5-year survival rate in stage 2 prostate cancer age 70 years or more treated by EBRT or Androgen deprivation therapy (p > 0.05)
Survival of Localized Prostate Cancer patients age ≥ 70 yr treated by EBRT or ADT
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The androgen deprivation The androgen deprivation syndromesyndrome
• Loss of libido• Erectile impotence• Decreased energy
- Metabolic syndrome- Osteoporosis / fracture- Loss of muscle mass- Weight gain- Anaemia- Alteration in lipid
profile- Depression, personality
change
What patients expect What they also get
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(Calais da Silva FEC et al, Eur Urol 2009)
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TREATMENT OPTIONS EAU 2008TREATMENT OPTIONS EAU 2008LOCALLY ADVANCED (grade A recommendation):• T3-4, N0, M0
– Radiotherapy > 70 Gy for T3 with life expectancy >5-10 yr
– Hormonal treatment for T3-4 & PSA > 25 ng/ml– Combination Radiotherapy + Hormonal treatment
better than RT alone• Any T, N1, M0
– Hormonal therapy as standard treatment
ADVANCED DISEASE
Hormonal therapy as standard treatment
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Hormonal treatment:Hormonal treatment:
• Bilateral orchiectomy
• Oestrogens (DES)
• LHRH agonists• LHRH antagonists• Anti-androgens
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The androgen deprivation The androgen deprivation syndromesyndrome
• Loss of libido• Erectile impotence• Decreased energy
- Metabolic syndrome- Osteoporosis / fracture- Loss of muscle mass- Weight gain- Anaemia- Alteration in lipid
profile- Depression, personality
change
What patients expect What they also get
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Recent evidence on IAB in advanced Recent evidence on IAB in advanced prostate cancer patientsprostate cancer patients
• Testosteron recovery:± 90% patients recovered to normal testosteron levels within 18 weeks after 1st ON treatment cessation
• Disease progression & survival:No significant differences between IAB and CAB in term of:
- median time to progression- progression free survival- overall survival
• Tolerability & QoL:- Side effects (hot flushes, gynecomastia, headaches) were significantly more in CAB- Significantly better sexual activity & emotional function were found in patients with IAB therapy(Abrahamsson P-A, Eur Urol, 2010)
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IAB vs Orchydectomy
p = 0.35
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IAB in advanced Prostate CancerM1 (a/b/c)
Intermittent hormonal therapy
Successful 1st ON treatment(9 months)
Failed within 1st ON treatment
1st OFF treatment
orchydectomyRe-start if PSA ± 15ng/ml
Failed
Successful 2nd ON treatment (9 months)
2nd OFF treatment
3rd ON treatment
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Recent evidence on IAB in advanced Recent evidence on IAB in advanced prostate cancer patientsprostate cancer patients
• IAB seems to be as effective as continuous AB with tolerability & QoL advantages
• When to stop & ON treatment duration:- PSA < 4 ng/ml- 9 months therapy
• When to re-start: PSA ± 15 ng/ml.
(Shaw G and Oliver RTD, Surgical Oncology 2009; Abrahamsson P-A, Eur Urol 2010)
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Definition of HRPC (Hormone Refractory ProstateCancer or Androgen Independent Prostate Cancer)
1. Serum castration level of Testosteron2. Three consecutive rises of PSA 2 weeks apart
resulting in two 50% increases over the nadir3. Antiandrogen withdrawal for at least 4 weeks4. PSA progression despite secondary hormonal
manipulations5. Progression of osseous or soft tissue lesions
(EAU Guidelines 2008)
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Systemic non-hormonal therapy in HRPC
• Cytotoxic chemotherapy• Bone-targeted treatments• Immunotherapy• “Targeted” therapy
Maintain androgen deprivation !!(LHRH analogue or Orchydectomy bilateral)
EAU Guidelines 2008 & Nelson WG et al. Prostate Cancer 6th Int’l Consultation 2005
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Hormone refractory prostate cancer (HRPC)Hormone refractory prostate cancer (HRPC)Take home message (3):
• Make sure to have an increasing PSA during treatment even after discontinuation of anti-androgen
• Testosteron level should be < 20 ng/dL (otherwise performed an orchydectomy or give additional LHRH analogue)
• Start with systemic non-hormonal therapy• Continue with LHRH analogue or perform
bilateral orchydectomy