1

Rak stercza



Diagnostyka



Stopień zaawansowania



Strategia leczenia



Zasady hormonoterapii



Leczenie chirurgiczne

2

Patologia nowotworów
stercza



Łagodne - Łagodny Rozrost Stercza

(BPH)



PIN (prostatic intraepithelial

neoplasia, intraductal dysplasia,

atypical primary hyperplasia) –

prekursor raka stercza



Low grade



High grade

3

Patologia nowotworów
stercza



Pierwotne nowotwory nabłonkowe



Adenocarcinoma (pow. 90%)



Squamous and adenosquamous ca

(do3%)



Inne nabłonkowe



Nowotwory przerzutowe lub wtórne (Rak

pęcherza moczowego, Rak oskrzela,

Czerniak )



Nowotwory nienabłonkowe - mięsak



Chłoniak

4

Diagnostyka raka stercza



Badanie podmiotowe i przedmiotowe, DRE

(Digital Rectal Examination)



Badania laboratoryjne



PSA



Fosfataza zasadowa



Sterczowa Fosfataza kwaśna



Badania obrazowe



USG (Przezbrzuszne, Transrektalne)



Scyntygrafia kośćca



CT, MRI (endorectal coin MRI)



RTG kości, klatki piersiowej, urografia



Cystoskopia

5

Objawy raka stercza



Objawy przeszkody podpęcherzowej



Dysuria, zatrzymanie moczu (częściowe,

całkowite), częstomocz, bolesne oddawanie

moczu,



Zakażenie moczu



Krwiomocz (mikro- i makroskopowy)



Ból (kości, krocze, okolica krzyżowa i

lędźwiowa)



Obrzęki (moszna, podudzia)



Bezmocz, mocznica



Niedokrwistość, wyniszczenie

6

Definicje

Definicje

Choroba
Wynik badania nieobecna obecna
Dodatni

a b

Ujemny

c d

Suma

a+c b+d



Czułość (Sensivity)=a/a+c Swoistość (specifity)=

d/b+d



Pozytywna wartość prognostyczna= a/a+b



Negatywna wartość prognostyczna = d/d+c



Dokładność (Accuracy) = a+d/a+b+c+d

7

Drogi rozsiewu i
przerzutowania raka
stercza



Miejscowo



Naciek przekraczający torebkę stercza



Naciekanie pęcherzyków nasiennych, pęcherza

moczowego, stercza



Naczynia i węzły chłonne („stacje”)



Zasłonowe, okołopęcherzowe, biodrowe wewn. i zewn.



Przedrzyżowe, kulszowe, pachwinowe, biodrowe

wspólne, okołoaortalne



Śródpiersiowe, nadobojczykowe



Naczynia krwionośne



Kości



Płuca, wątroba, OUN, nadnercza, prącie, jądra

8

DRE in PC diagnosis



Czułość- ~50%



Swoistość– ~80%



Positive predictive value – 21%-53%



DRE misses 23%-45% of PC found Bx because of PSA



PC detected only by DRE is pathologically advanced in

more than 59%



ECE:



Sensitivity – 37%-52%



Specificity – 81%



SV+:



Sensitivity – 17%



Specifciity – 55%

9

Prostate specific antigen
(PSA)



Glicoprotein, 34 kDa, 240 aminoacids,

component of semen, T

1/2

=2,2-3,2 d



Marker specyficzny dla narządu



Nie specyficzny dla raka stercza



Wolne i związane PSA



25% chorych na raka sterczama PSA<4

ng/ml



Metody zwiększające swoistość badania

PSA

10

Tkanki wydzielające PSA



Normal prostate



PC



BPH



Periurethral glands



Perirectal glands



Bladder adenocarcinoma



Cyctitis cystica



Skene glands



Endometrium



Normal mammal gland



Kidney cancer



Suprarenal gland cancer

11

Badanie stężenia PSA w
surowicy



RIA, EIA, LIA, FIA



Monoclonal antibodies (Hybritech,
4ng/ml)



Policlonal antibodies (Pros-Check,
Yang Bellevue, 2,5ng/ml)



Abbot, Delfia

12

Zakresy norm PSA



0,0-4,0 ng/ml – 100% zdrowych

mężczyzn <40rż



0,0-4,0 ng/ml – 97% zdrowych

mężczyzn >40rż



4,0-10,0 ng/ml – 3% zdrowych

mężczyzn >40rż



Dobowe i roczne wahnięcia - bez

znaczenia

13

PSA

and PAP czułość, swoistość,

pwp, nwp i dokładność w
diagnostyce raka stercza

sPSA>5 ng/ml



Czułość: 75%



Swoistość: 53%



pwp: 83%



nwp: 51%



dokładność: 69%

sPSA>10

ng/ml



Czułość: 65%



Swoistość : 87%



pwp: 93%



nwp: 46%



Dokładność: 71%

PAP>4 u/l



33%



100%



100%



34%



49%

PAP>8 u/l



20%



100%



100%



30%



40%

14

PWP w raku stercza w zależności
od zakresu normy PSA



0-4 ng/ml: 19%



4-10 ng/ml: 14%



>10 ng/ml: 67%

15

PSA – metody zwiększające
swoistość



Normy PSA w zależności od wieku



Gęstość PSA (PSA density -PSAD)



Szybkość wzrostu stężenia PSA (PSA velocity PSAV)



Stosunek PSA niezwiązanego do całkowitego (f/t

PSA)



Gęstość PSA strefy przejściowej (PSAD of transition

zone PSADTZ)



Przewidywane stężenie PSA (predictive sPSA pPSA )

– Objętość stercza (cm

2

)x0,12

16

Normy PSA w zależności od
wieku



40-49rż 0-2,5 ng/ml



50-59rż 0-3,5 ng/ml



60-69rż 0-4,5 ng/ml



70-79rż 0-6,5 ng/ml

17

Gęstość PSA
(PSA density - PSAD)



Szara strefa (4-10 ng/ml, 2-10 ng/ml)



Użyteczna, gdy 4 ng/ml<PSA<10 ng/ml



PSA/prostate volume (ng/ml/cc)



BPH<0,15ng/ml/cc



PC0,15 ng/ml

18

Szybkość wzrostu sPSA
(PSA velocity PSAV)



Procentowa lub bezwzględna
wartość wzrostu sPSA (%/r, ng/ml/r)



BPH<20%/r or <0,75 ng/ml/r



PC20%/r or 0,75 ng/ml/r

19

Stosunek PSA wolnego do
całkowitego (f/tPSA)



Wyższy poziom odcięcia

>25%

(bardziej swoisty) przy sPSA 2-10

ng/ml – w 95% BPH, można

uniknąć 30% biopsji



Niższy poziom odcięcia

<10%

(bardziej czuły) przy sPSA 2-4

ng/ml – w 60% PC



Nowa szara strefa – 2-4 ng/ml

20

Gęstość PSA strefy
przejściowej (PSADTZ)



BPH < 1,393 ng/ml/cc



PC  1,393 ng/ml/cc

21

Wpływ procedur na stężenie
PSA



DRE – mały wpływ



Cystoskopia – 4x wzrost



TRUS – mały wpływ



TURP – nawet 53x wzrost, następne
spadek



Biopsja stercza – 57x wzrost



Cewnikowanie pęcherza moczowego

22

USG



Przezbrzuszne



Wodonercze, zatrzymanie moczu, naciekanie

pęcherza moczowego



Bez znaczenia we wczesnym wykrywaniu raka stercza



TRUS



Brak możliwości zobrazowania wczesnych postaci

raka stercza



Zmiany hypoechogeniczne – 2x częściej rak stercza



Tylko 17% zmian hypoechogenicznych zawiera raka

stercza



50% niewyczuwalnych PC>1 cm – nie jest

uwidacznianych w TRUS

23

CT, MRI, X-ray



CT, MRI – nie poprawiły oceny
miejscowego zaawansowania chorogy



Niedostateczna czułość i swoistość do
oceny ECE or N+



IVP – ograniczona wartość



Każda metoda ma ograniczoną wartość

24

Pwp sPSA, DRE, TRUS w
diagnostyce raka stercza



sPSA>10 ng/ml



DRE-, TRUS-: 31%



DRE+, TRUS+: 80%



DRE-



sPSA<4 ng/ml: 2,5%



4 ng/ml<sPSA<10 ng/ml: 5,5%



sPSA>10 ng/ml: 10%



DRE+



4 ng/ml<sPSA<10 ng/ml: 38%



sPSA>10 ng/ml: 65%

25

Diagnostyka raka stercza



Biopsja



Kluczowe znaczenie w procesie

diagnostycznym



„Ślepa”



Transperineal



Tranrectal



TRUS



Transperineal



Transrectal



Aspiracyjna



Fine-needle, core

26

PC diagnosing algorithm

PSA

DRE

Diagnostic

procedure

Under age-

specific
reference

range

Negative

sPSA and DRE

every year

Above age-

specific
reference

range

Negative

TRUS guided

biopsy
(sextant) +

biopsy TZ

Any PSA

positive

TRUS guided

sextant biopsy

27

Staging and strategy of
the treatment of prostatic
malignancies

Romuald Zdrojowy
Janusz Dembowski

Clinic of Urology, Wrocław

Medical University, Poland

28

PC staging



TNM classification (UICC/AJC) 1992/1997



T – primary tumour



N – regional lymph nodes status



M – non-regional lymph nodes or distant
metastases



Clinical staging (TNM)



Pathological (microscopic) staging
(pTpNpM)

29

Clinical staging procedures



Primary tumour status (T)



DRE



TRUS



sPSA, grading (Gleason sc, Mostofi system)



Cystoscopy, IVP, CT, MRI, MRI endorectal coil –

optional



Regional lymph nodes status (N)



sPSA, grading (Gleason sc, Mostofi system)



USG, CT, MRI



Pelvic lymphadenectomy (laparoscopic, open)



Aspiration biopsy, lymphangiography?



Non-regional lymph nodes or distant metastases



sPSA, AlkP, grading (Gleason sc, Mostofi system)



Bsc, X-ray



USG, CT, MRI, chest X-ray

30

Diagnostic value in T
staging



DRE



ECE:



Sensitivity: 37%-
52%



Specificity: 81%



SV+:



Sensitivity: 17%



Specificity: 55%



TRUS



ECE:



Sensitivity: 66%-92%



Specificity: 46%-94%



SV+:



Sensitivity: 29%-33%



Specificity: >90%

31

Diagnostic value in T
staging



MRI endorectal magnetic coil:



ECE: sensitivity

38%

, specificity

95%



SV+: sensitivity

50%-83%

, specificity

88%-97%



CT:



ECE: sensitivity

55%-75%

, specificity

60%-73%



SV+: sensitivity

33%-36%

, specificity

60%-96%

32

Diagnostic value in N
staging



CT:



Sensitivity –

27%-50%



Specificity –

66%-96%



MRI:



Sensitivity –

44%-69%



Specificity –

95%-100%

33

Diagnostic value in M
staging



RTG:



Sensitivity –

50%



Specificity –

90%-100%



Bsc:



Sensitivity –

75%



Specificity –

60%-70%

34

PC clinical staging



Clinical downstaging – up to 60%



Clinical upstaging – 5%-30%



Accuracy of clinical staging (T, N) – Partin’s

table (JAMA, 1997, 277, 1445; J. Urol.,

1993, 150, 110), Humphrey, Kleer,

Oesterling, Bluestein



Clinical staging acc. to T – „no better than

the flip of the coin” (Badalament R. A., J.

Urol., 1996, 156, 1375)



Clinical N – Partin’s table

35

General principles PC
treatment



Radical treatment (curative intent: RP, RTX)



Organ confined (T1-2N0M0)

Organ confined (T1-2N0M0)



Age (traditionally 70y)



Life expectancy > 10y



Good general condition



Patient agreement for aggressive treatment



Palliative treatment (watchful waiting, hormonal,

palliative surgery, chemotherapy)



Locally advanced or disseminated (T3-4NxMx,

Locally advanced or disseminated (T3-4NxMx,

TxN+M+)

TxN+M+)



Short life-expectancy



Advanced age

36

PC natural history – main
stages



Incidental PC – T

1(a,b,c)

N

0

M

0



Organ-confined PC – T

2

N

0

M

0



Locally advanced – T

3-4

N

0

M

0



Disseminated PC – T

x

N

+

M

+

(T

1-

2

N

+

M

+

, T

3-4

N

+

M

+

)

37

PC evolution phases



Radical treatment (organ-confined

forms)



Induction phase – up to 30y



In situ phase – 5-10y



Invasion phase – 1-5y



Palliative treatment (disseminated

forms)



Dissemination phase – 1-5y

38

T at the diagnosing
moment



80th



C+D: 50%-75%

C+D: 50%-75%

(Jewett, Andriole, Chodak: J.

Urol., 1984, 131, 845)



C+D: 80%

C+D: 80%

(Pawlicki: Ter. Leki, 1988, 16, 57)



90th



N+M+ or T3-4: 35%-40%

N+M+ or T3-4: 35%-40%

(Schröder, van den

Ouden, Davidson: Eur. Urol. Up. Series, 1992, 1,

18)



N+M+ or T3-4: 12%-18%

N+M+ or T3-4: 12%-18%

(Gibbons, Lerner: J.

Urol., 1995, 154, 1447. Cancer, 1996, 78, 2455)



N+M+ or T3-4: 90%

N+M+ or T3-4: 90%

(Madej G.: Nowotwory,

1995, 45, 93)



T2 in 9%

T2 in 9%

(Borówka A.: Nowa Med., 1996, 2, 20)

39

Modern staging of PC



Biopsy feature



Capsular perforation on biopsy



Gleason score on biopsy



Percentage of PC in biopsy cores



Molecular staging

40

PC modern staging (cont.)



Biopsy feature



Inadequacy of PSA, PSAD, Gleason sc
in ECE and final pT prediction



>4/6 pos. Bx  large volume tumour

and high risk ECE, pN+



1/6 pos. Bx  unfavourable pT in

20%-30%



% pos. Bx, length of PC tissue

41

PC modern staging (cont.)



Capsular perforation on bx



PC present among fat cells



Powerful feature with % pos. Bx, sPSA



2/3 criteria present  85% progress

after RP vs 14% if no criterion present

42

PC modern staging (cont.)



Gleason score on bx



Biopsy Gleason sc is identical to specimen
in only 35%-48%



Underscored 40%-80%



Overscored 5%-14%



Best correlation in high Gleason sc
tumours



Correlation between Bx G and pG is poor
except very high and low Gleason sc

43

PC modern staging (cont.)



% of PC in biopsy cores



Should be used with conjunction with
other preoperative features



>3/6 pos. Bx – highly predictive for
high-volume tumour, SM+, pT

44

PC modern staging (cont.)



Molecular staging



RT-PCR assay – identifies PSA-
synthesizing cell in 100000 blood cells



PSMA – PSMA-nested RT-PCR assay
possible to detect PSMA-positive cells
in 67%-85% pts with metastatic PC
and in 40% with clinically localized PC

45

Principles of PC hormonotherapy
(HT)

Romuald Zdrojowy, Jerzy

Lorenz

Clinic of Urology, Wrocław

Medical University, Poland

46

PC hormonotherapy



Huggins, Hodges (1941) –
androgen dependence most PC



Aim HT – deprive tu cells of
androgens or their byproducts



Multiple points along the pathway
between production and
metabolism may be broken

47

Principles of PC HT



Androgens:



Testes – testosteron (92%-95%)



Adrenals – androstendione, DHA (3%-7%)



Male hormone regulation



hypothalamic-pituitar-gonadal axis



LHRH  LH  T



T bound to SHBG (97%), unbound T (3%) –

functionally active



Serum T concentration – 5,721,35 ng/ml



Prostate - T  DHT (5-reductase)

48

Principles of PC HT



Prolactin:



Stimulation the formation of T and
androgen by testes and adrenals



Potentiating T action on prostatic
tissue



Growth factors (EGF, FGF, ILGF1
and 2, TGF) – act through

membrane receptors

49

Principles of PC HT



~80% of PC have favourable response

to adequate HT



Criteria of HT response



EORTC



NPCP



Duration of HT response variable



Time to clinical progression and death –

18-24 and 30-36 months



Hormone refractory PC (HRPC)

50

Principles of PC HT



Reduction of androgenic support:



Removal of the primary source of circulating

androgens (surgical castration)



Removal or suppression of LHRH and reduction of

testicular T (estrogens, LHRH analogs,

cyproterone acetate, LHRH antagonists



Direct inhibition of androgen synthesis at cellular

level (CA, aminoglutethymide, spironolactone)



Blocking androgens or their effect at a cellular

level (steroidal-CA, megestrol acetate,

nonsteroidal-flutamide, nilutamide, bicalutemide)



Maximal androgen blockade

51

The forms of HT



Orchiectomy (castration)



Clinical answer: 70%-80%



5-years cancer specific survival:



Locally advanced (T

3-4

N

0

M

0

) ~30%



Disseminated (TxN+M+) ~20%

52

Forms of HT - estrogen
therapy



Mechanism of action:



Pituitary - LH



Leydig cells – inhibition of steroid sex hormons

metabolism



Prostate – inhibition of DNA polimerase and 5-

reductase



 TeBG  free T



PRL



5-years cancer specific survival:



T3-4N0M0 – 30%



TxN+M+ - 20%-30%



Clinical answer: 70%-80%

53

Forms of HT -
antiandrogens



Steroidal:



Cyproterone acetate



Medroxyprogesterone acetate



Chlormadinone acetate



Non-steroidal:



Flutamide



Nilutamide



Bicalutamide

54

Antiandrogens – mechanism of
action



Peripheral:



On steroid receptors in cytosole –
inhibition DHT-receptor complex
synthesis



Inhibition of binding DHT-receptor
complex to nucleus chromatine



Central:



LH  T

55

5-year cancer specific
survival



T3-4N0M0: 23%-60%



TxN+M+: 10%-42%



General answer to HT in advanced
PC: 60%-87%

56

Surgical treatment of the
prostatic tumours

Romuald Zdrojowy

Tomasz Szydełko

Clinic of Urology, Wrocław

Medical University, Poland

57

Surgery of prostatic
malignanciec



Surgery for establishing diagnosis



Surgery for staging



Surgery for primary control



Surgical palliation of extended disease

58

PC clinical organ-confined

Cancer specific survival

Cancer specific survival



Incidental PC:



T1a – 5y:

98%

, 10y:

>95%



T1b – 5y:

80%-85%

, 10y:

75%



Organ-confined PC:



T2N0M0 – 5y:

89%

, 10y:

51%

59

Radical prostatectomy



Reserved for men who are likely to be cured and

will live long enough to benefit from the cure



Radical treatment (curative intent: RP, RTX)



Organ confined

Organ confined



T1bN0M0Gx –T2N0M0Gx

T1bN0M0Gx –T2N0M0Gx



T1aN0M0G3 (Epstein J. I.: J. Urol., 1994, 151, 1587.

T1aN0M0G3 (Epstein J. I.: J. Urol., 1994, 151, 1587.



Age (traditionally <70y)



Life expectancy > 10-15y; 70yo-12,1y, 75yo-10y



Prognostic factors (stage, grade, sPSA – Partin’s table)



Good general condition



Patient agreement for aggressive treatment

60

Radical prostatectomy -
approaches



Retropubic (92%) (AUA, San Diego Ca)



Perineal (7%) (AUA, San Diego Ca)



Transcoccygeal (<1%)



Minimal invasive, skin incision<8 cm
(Puppo P.: Eur. Urol., 2000, 37, S2,
161)



laparoscopic

61

Lymphadenectomy - types



Classical (obturator, int, ext and

common iliac nodes)



Broaden (as in classic+preischiadic and

presacral nodes – Golimbu, Morales)



Modified (obturator, hypogastric nodes)



Obturator (obturator nodes)



Laparoscopic (Moravek P.: Int. Urol.

Nephrol., 1987, 19, 315)



Minilaparotomy (Steiner M., Marshall F.:

J. Urol., 1993, 41, 201)

62

Criteria for lymphadenectomy
performing

Therapeutic decision

Criteria



RRPclassical L without frozen section



RPPwithout pelvic L

PSA<10, Gleason sc<7,
T<2c



RRPclassical L or minilaparotomy L

with frozen section



RPPevery pelvic L with frozen section

or as the additional procedure

PSA10 or Gleason sc7
or T2c



RRPlaparoscopic L (with frozen

section or as aditional procedure) or
minilaparotomy L



Every RPCT or MRI with aspiration

biopsy

PSA50 or (PSA20 and
Gleason sc7) or
(PSA10 and Gleason
sc8)

63

Radical retropubic
prostatectomy (RRP)

The varieties of RRP



Ascendens (retrograde) – perform
from prostate apex



Descendens (antegrade) – perform
from bladder neck (Petros J., Catalona
J. J.: J. Urol., 1991, 145, 994.)

64

The varieties of RRP



Nerve-sparing rrp



Anatomic rrp – Walsh & Donker



De Kernion – suture of penis deep dorsal

vein complex



Ruckle – early incision of endopelvic fascia



Unilateral nerve-sparing rrp



Broaden prostate excision



Stamey – „super radical prostatectomy”



Stephenson – „wide excision, non nerve-

sparing rrp”

65

Anatomical considerations



Endopelvic fascia



Puboprostatic ligaments



Neurovascular fascicles



Denonvillier’s fascia (lamina
ant.=prostatoperitoneal membrane)



Proust space



Arteries and veins

66

Postoperative procedure



Thrombo-embolic prophylaxis



Low molecule heparine



Prophylactic compress devices



Early setting on foot



Nutrition – 1st postoperative day



Bladder catheterisation: 7-21 days



Drains

67

Post-rrp complications



Morbidity and mortality: <1% (0,2%)



Intraoperative:



Haemorrhage (penile deep dorsal vein
complex, Santorini plexus,
lymphadenectomy)



Obturator nerve injuries



Rectal injuries (0%-5%)



Ureter injuries (0%-2%)

68

Post-rrp complications



Early postoperative



Delayed haemorrhage (<0,5%)



Urine leakage



Stercoral fistula



Limfocoele



Vein thrombosis (3%-12%,
asymptomatic even up to51%)



Lung embolism (2%-5%)

69

Post-rrp complications



Late postoperative



Urine incontinence



Complete: 0%-5%



Stress: 3%-20%



Erectile dysfunction (prognostic
factors: age, pT, nerve-sparing rp)



Urethro-vesical stricture

70

Radical perineal
prostatectomy



Indications:



T1b-T2, T1aG3



Without lymphadenectomy – sPSA<10
ng/ml and Gleason sc<7 (G1-2)



Prostate volume < 50 cc



Age < 70y, life-expectancy >15y



No coxarthrosis (lithotomy position)

71

Oncological results (John
Hopkins)



pT2 – 43%, focal pT3 – 15%, established pT3 – 42%,
SM+ 4,6%, pT3c – 2,4%, pN+ 2,8%



10y observations:



No PSA rise: 70%



Isolated PSA rise: 23%



Distant metastases: 7%



Local progression: 4%



10y observation without PSA rising probability:



pT1-2: 85%, focal pT3: 82%



Established pT3: Gleason sc 2-6: 54%, 7-10: 42%

72

Oncological radicality missing
procedures



Focal pT3, SM-: surveillance (sPSA, DRE, US,

TRUS, Bsc)



Established pT3, SV+, SM+, pN+:



Surveillance (?)



Early adjuvant teatment (?)



No local radicality (pT3, SM+) – RTX



Disseminated disease (pN+, SV+) – AHT



Progression up to 9-12 months, high Gleason sc:

general progression more probably – AHT



Progression > 12 months, low Gleason sc: local

progression more probably- RTX

73

Minimally invasive alternative
treatment options



Cryosurgical ablation (CSAP)



Brachytherapy by transperineal US-
guided radioisotopes implantation



High-intensity focused US (HIFU)



Radiofrequency interstitial tumour
ablation (RITA)

74

Surgical palliative treatment
of PC



Urine retention:



TUR-P (tunnelisation)



Urethral stents



Ureterohydronephrosis, anuria, uraemia



Percutaneous nephrostomy



Ureteral catheterisation



Haematuria



TUR-P



Baloon compression