short notes about prostate cancer , epidemiology , histopathology and diagnosis

1. PROSTATE CANER
PREPARED BY
DR.AHMAD SHAMOUT
3RD YEAR RESIDENT
RADIOTHERAPY DEPARTMENT
AL-BASHEER HOSPITAL
M.O.H

2. • SEMINAR OUTLINE:
• BRIEF HISTORY ABOUT OUR HIGHLIGHTED
CASE
• EPID.&PATHOLOGICAL KEY POINTS
• HOW THE PATIENT BEING APPROACHED
• NARRATION OF THE PATIENTS
• MANAGEMENT OF THE HIGH RISK
PATIENTS
• MONITORING

3. CASE
• Mr. YOUSEF SA’AFEEN 65 YRS OLD MALE
PATIENT, PREVIOUSLY HEALTHY, NON-SMOKER
• PT STARTED TO HAVE POLYURIA, HESITENCY &
POOR STREAMING, AND DIAGNOSED TO HAVE
PROSTATIC CANCER (ADENOCARCINOMA).
G/S 4+5=9, PNI +VE, LVSI+VE, IPSA= 147ng/ml
PRESENTED ALSO WITH BONE METS.

4. EPIDEM. & PATH. KEYPOINTS

5. Prostatic plexuses
• The Prostatic Plexus is continued from the lower part of the pelvic
plexus. It lies within the fascial shell of the prostate.
• They are distributed to the prostate vesiculæ seminales and the
corpora cavernosa of the penis and urethra.
• The nerves supplying the corpora cavernosa consist of two sets, the
lesser and greater cavernous nerves, which arise from the forepart
of the prostatic plexus, and, after joining with branches from the
pudendal nerve, pass forward beneath the pubic arch. Injury to the
prostatic plexus (during prostatic resection for example) is highly
likely to cause erectile dysfunction. It is because of this relationship
that surgeons are careful to maintain the integrity of the prostatic
fascial shell so as to not interrupt the subsequent neuropathways to
the pudendal nerve

6. PELVIC LN

8. *Prostate is the largest accessory gland of
the male genital system. It is located in the
pelvis, with its base superior and its apex
inferior .It is a conical organ that surrounds
the prostatic urethra.
*MOST COMMON CANCER (NON CUT.) IN
MEN AND THE 2ND MOST COMMON
CAUSE OF CANCER RELATED DEATH.
*INCIDENCE: 95% OF PROS. CA OCCUR
BETWEEN 45-89YRS.
1/10000BELOW 40

9. • 1/103 40-59YRS
• 1/8 60-79
• RF: INC. LIFE EXPECTANCY, UTILIZATION OF
PSA AND SCREENING PROG.S, AFRICAN
AMERICAN, FAMILY HX, PROSTATIC PROBLEMS

10. • More than 95% of prostate cancers are adenocarcinomas,
and ~4% are transitional cell cancers .Others are
neuroendocrine carcinomas (small cell) and sarcomas.
• intraepithelial neoplasia (PIN) is a precursor lesion.
• PIN is cytologically similar to prostate cancer, but is
differentiated from cancer by the presence of an intact
basal membrane layer.
• PIN is generally classified into either high-grade PIN
(HGPIN) or low-grade PIN(LGPIN).
• The clinical importance of this distinction is that HGPIN is
associated with cancer in 80% of cases, while this ratio is
20% for LGPIN.
• Prostate cancer develops from the peripheral zone in 70%
of cases, from the central zone in 15–20% for central zone,
and from the transitional zone in 5–10%.
• Most prostate cancers are multifocal, and can be found in
different zones of prostate with various grades.

12. • 3 ZONES: PERIPHERAL Z.( 75% OF CACERS),
CENTRAL Z.(25%) & TRANSITIONAL Z.( INNER
PART AND PERI URETHRAL, HERE NO TURP
BECAUSE ITS MULTIFOCAL).
• 5 LOBES( 2 LAT.,1 POST., 1 ANT., 1 MEDIAN)
• POST. LOBE IT’S THE ONE FELT BY DRE.
• 50-80% OF TU. AT THE APEX & 85% OF PT.S
HAVE MULTIFOCAL DISEASE.
• AT THE APEX THE CAPSULE NOT WELL-
DEFINED SO ITS DIFFICULT TO ASSESS ECE.
• ECE IS COMMON AT THE POSTEROLATERAL
PART DUE TO PENETRATION BY NERVES

13. APPROACH
• H&P:
-F.Hx: THE CLOSER THE EARLIER ONSET& THE
MORE FFECTED FAMILY MEMBERS THE HIGHER
THE RISK.
- MEDICATIONS
- DRE: TO ASSESS COSISTENCY OF PROSTATE,
SIZE, PRESENCE OF NODULES, INVOL. OF LAT.
SULCI OR SEMINAL VESICLE

14. DRE: WHEN TO BE WORRIED???

15. • PROSTATE CANCER: STONY HARD
• Benign prostatic hyperplasia (BPH), or an
enlarged prostate gland, is a common non-
cancerous condition in men over 50. The
enlargement is often detectable with a DRE.
• Previous prostate surgery produces a DRE where
the area of the prostate gland feels hard and flat.
The normal prostate landmarks are lost when the
prostate gland is completely or partially removed.
• Prostate infections: Acute bacterial prostatitis
usually produces an extremely tender, swollen
prostate gland that is partially or totally firm,
irregular and warm to the touch

16. • Prostatic or rectal calcifications (stones):
Although most prostatic calculi cannot be
found by means of DRE, some can. It is more
common to discover rectal calcifications,
small, hard deposits in the rectal blood
vessels. Rectal stones are unrelated to any
prostatic conditions.

17. • IF DRE +VE (regardless of psa) TRUS-
GUIDED Bx
• IF –VE DO PSA :
--- TPSA ≤2.5 & PSAV˂0.35ng/ml/year---- FU
WITH DRE & PSA ANNUALLY GIVEN THAT PSAV
˂0.35ng/ml/year OR GO TO BX
---2.6-4ng/ml------ bx WITH CONSIDERATION TO
AGE≥75,COMORBIDITY,PFPSA,FHX&ETHNICITY
---4-10NG/ML----BX----IF –VE---FU(6-12MO)
IF +VE ----TREAT AS CANCER

18. • WE CAN USE FPPSA AS FOLLOWING:
1. ≤10%-------Bx
2. 10%˂FFPSA≤25%-----FU(DRE &PSA)
3. >25%-----FU(ANNUAL DRE,PSA&FPPSA)
----IF PSA>10---- Bx

19. PSA
• PSA is a neutral serine protease that liquifies
seminal coagulate by hydrolyzing seminogelin
I and II, which are seminal vesicle proteins.
• Only a small portion of the PSA is found in its
free form, termed free-PSA (f-PSA), as most of
it is bound to alpha 2-macroglobulin (AMG)
and alpha 1-antichymotrypsin (ACT).
• The half-life of PSA is around 2.2–3.2 days,
and reaches its lowest level 2–3 weeks after
radical prostatectomy (RP).

20. PSA
• SENSITIVE BUT NOT SPECIFIC( 15% FALSE +VE)
• IT AN RISE IN MANY CASES AS:
INFECTIONS, BPH,RECENT DRE, RECENT
EJACULATION, AFTER PROSTATIC Bx(6-8MO),
RARELY IN PANCREATIC,PAROTID & BREAST CA.

21. PSA CLINICAL USES
1. DETECT PRIMARY OR RECURRENT TUMORS
OF VERY LOW VOLUMES.
2. USEFUL FOR FOLLO-UP.
3. SEARCHING FOR METS. IN ASYMP. PT WITH
PSA LESS THAN 10 NG/ML NOT INDICATED
ROUTINELY.
*25% OF PT.S WITH +VE Bx HAVE SERUM PSA
LESS THAN 4NG/ML.
* WHEN PSA COMBINED WITH TRUS-GUIDED Bx
CA IS DETECTED IN 20% OF PT.S WITH PSA 4-
10NG/ML & 60% WITH PSA MORE THAN 10%

22. PSA KINETICS
• TPSA:
• TPSA 4ng/ml is the clinical threshold, specifity
increase when PSA correlated with DRE

23. • FREE PSA PERCENTAGE: % OF PROTEIN-
UNBOUND PSA LESS THAN 0.15 ASS. WITH
PROST. CA.
• PSA DENSITY: PSA/GLAND VOLUME , ITS USED TO
IMPROVE THE +VE & -VE PREDICTIOVE VALUES
WHEN TPSA 4-10ng/ml
• PSA VELOCITY: RISE OF PSA AS A FUNCTION OF
TIME.
---- IF TPSA LESS THAN 4NG/ML PSAV OF
≥0.35ng/ml/y IS SUGGESTIVE OF CA.
---- IF TPSA 4-10ng/ml PSAV OF ≥0.75ng/ml/y is
suggestive
---- IF TPSA > 10ng/ml PSAV NOT USEFUL

24. • PT MUST BE ABSTINENT FOR 48 HRS.
• PAY ATTENTION TO MEDICATION THAT LOWER
PSA AS:
-----5ARI(FINSTERIDE& DUTASTERIDE)
----- KETOCONAZOLE

25. IMAGING
• An assortment of imaging technologies, including 2D,
3D,and Doppler ultrasound, CT, and MRI, has been
extensively evaluated in an attempt to improve
staging accuracy, but are not considered
replacements for DRE
• Among these tools, TRUS and MRI permit optimal
visualization of prostate anatomy relative to CT
• Surface and endorectal MRI coils can yield
complementary information, with the latter
providing fi ne resolution of the prostatic structures
and the former information on the adjacent organs
and regional lymph nodes

26. • T2-weighted sequences allow visualization of the
zonal anatomy, vas deferens and seminal vesicles,
neurovascular bundles, and penile bulb
• MRI allows detection of seminal vesicle invasion
and extraprostatic disease, although MRI staging
is made difficult by postbiopsy hemorrhage
• Anatomic T2-weighted MRI imaging is a sensitive
diagnostic and technique whose specifi city and
diagnostic accuracy can be enhanced by magnetic
resonance spectroscopy(MRS) and/or dynamic
contrast-enhanced techniques (DCE-MRI)

27. BIOPSY
• GOLD STANDARD METHOD FOR Dx.
• Bx IS TAKEN WITH ASSISSTANCE OF TRUS
• CANCER APPEAR HYPOECHOIC

28. • 30% OF CA APPEARS ISOECHO.
• WHEN PSA MORE THAN 4 THE EXPECTED
YEILD OF DX 24% BUT IF PSA MORE THAN 4
AND SUSP. DRE AND HYPOECHO. LESION THE
YEILD RISES TO 45%

29. TYPES OF BX
1. SEXTANTS: OBTAINIG SIX CORES FROM MID
LOBAR PERIPHERAL ZONE ALONE( FAILURE
RATE 10-30%)

30. • 1&5 LATERAL PERIPHERAL ZONES
• 2&4 MID PERIPHERAL ZONES
• 3 TRANSITIONAL ZONE

31. • HERE SEXTANTS TAKEN FROM AREAS 2&4
2.EXTENDED-PATTERN BX(12 CORES):
---- SEXTANT(6CORES)
----LPZ(6CORES)
----LESION-DIRECTED AT PALPABLE NODULE OR
SUSPICIOUS IMAGE

32. WHAT EXPECTED TO BE FOUND
1. TYPE OF PATHOLOGY
2. GRADE(G/S)
3. NO. & LENGTH OF EACH CORE
4. LENGTH OF TU IN EACH CORE
5. PNI
6. LVSI
7. STAINING

33. GLEASON SCORE
• Histological evaluation provides important
prognostic information in prostate cancer
• The Gleason score is based on the degree of
loss of the normal glandular tissue
architectures
• The classic Gleason scoring diagram
shows five basic tissue patterns that are
technically referred to as tumor grades

34. • microscopic determination of this loss of
normal glandular structure caused by the
cancer is abstractly represented by a
grade
• a number ranging from 1 to 5, with 5 being
the worst grade possible

36. 1. SMALL UNIFORM GLANDS CLOSELY PACKED
2. MORE SPACES BET. GLANDS
3. INFILTRATION OF CELLS AT THE GLANDS
MARGINS
4. IRREGULAR MASSES OF CELLS WITH FEW
GLANDS
5. SHEETS OF CELLS WITH LACK OF GLANDS

37. HOW GS CALCULATED

38. • PRESENCE OF TERTIARY PATTERN OF (5)
SIGNIFICANTLY AFFECT PX ADVERSELY
• PT WITH LOW GS (4 OR LESS) SHOULD HAVE
BX REVIEW BECAUSE SOME PT.S WILL HAVE
NO CANCER BUT MOST OF THEM WILL HAVE
HIGHER GRADE CANCER
• PT WITH GS 7 AND WE FOUND A TERTIARY
PATTERN OF 5 WE MUST UPGRADE HIS GS TO
8

39. STAGING
• GATHERING ALL THESE DATA AND
PROCESSING IT CORRECTLY WE WILL BE ABLE
TO STAGE PT ACCURATELY AND NARRATE HIM
ACCORDING TO HIS CORRECT RISK GROUP IN
ORDER TO TREAT HIM WELL

43. NOMOGRAMS
• Partin nomograms predict pathologic stage (organ confined,
ECE,seminal vesicle invasion, or LN involvement) based on T stage,
GS, and pretreatment PSA
• Brignanti nomograms (using extended LN dissection) show higher
rates and support importance of obtaining larger # of LN (e.g., 28 to
detect 90%) to improve chance of detecting involvement
• Roach formulas estimate pathologic stage based on original Partin
data
• ECE = 3/2 × PSA + 10 × (GS-3)
• Seminal vesicle involvement = PSA + 10 × (GS-6)
• LN involvement = 2/3 × PSA + 10 × (GS-6)
• Kattan nomograms are computerized and predict primarily PSA
recurrence, but some also predict PFS as well as prostate cancer
specific mortality after RP, 3DCRT, or brachytherapy.

44. PATIENT NARRATION
• FOR TREATMENT PURPOSES PT.S
CATEGORIZED INTO 3 CATEGORIES:
A- CLINICALLY LOCALIZED
B- LOCALLY ADVANCED
C- METASTATIC

45. CLINICALLY LOCALIZED
• PT.S HERE ARE SUB-CATEGORIZED ACCORDING
TO RECURRENCE RISK INTO:
1- VERY LOW RISK GROUP:
---T1a
--- GS≤6
--- PSA˂ 10ng/ml
--- ˂3 +VE BX & ≤ 50% CANCER IN EACH ONE &
PSA DENSITY ˂ 0.15ng/ml/g

46. CLINICALLY LOCALIZED
2- LOW RISK:
--- T1-T2a
--- GS ≤6 &PSA˂10ng/ml
3-INTERMEDIATE RISK :
--- T2b,c OR
--- GS 7 OR
--- PSA 10-20ng/ml

47. CLINICALLY LOCALIZED
4. HIGH RISK GROUP:
--- T3a OR GS 8-10 OR PSA> 20

48. LOCALLY ADVANCED
• VERY HIGH RISK: T3b,T4

49. METASTATIC
• ANY T ,N1
• ANY T, ANY N, M1

50. TREATMENT OPTIONS
1--- SURGERY:
A-TURP-----> USED MAINLY FOR BPH NOT
RESPONDING TO MEDICATIONS.
B--- PROSTATECTOMY:
❶ RERTRO PUBIC RADICAL PROSTATECTOMY:
REMOVE PROSTATE THROUGH ABD. INCISION &
URETHRO-VESICAL ANASTOMOSIS, BLOOD
VESSEL TIED OFF&BILAT. NERVE BUNDLES
REMOVAL PLUS PLND.

51. TREATMENT OPTIONS
❷RADICAL PERINEAL PROSTATECTOMY: LESS
COMMON DUE TO DIFFICULT ACCESS TO LN
AND DIFFICULT TO AVOID NERVES
❸SUPRAPUBIC TRANS VESICAL PROST. OR
HRYNTSCHAK PROCEDURE
❹ROBOTICALLY-ASSISTED RADICAL
PROSTATECTOMY: --- LESS INVASIVE--- LESS BLD
LOSS--- RAPID RECOVERY BUT NO DIFFERENCE
IN ERECTILE FUNCTION RECOVER WITH RRP

52. TREATMENT OPTIONS
• ERECTILE FUNCTION RECOVERY DEPENDS ON:
----AGE AT RP
----PREOP. ERECTILE FUNCTION
----DEGREE OF NERNE PRESERVATION
*** C/I OF SURGERY:
---≥75 YRS
---LN METS.
---DISSEMENATED METS
---CO-MORBIDITIES

53. TREATMENT OPTIONS
C...PLND

54. 2.Androgendeprivation therapy
$$$ produce symptomatic relief in 80% of pt.s &
the improvement is dramatic.
Types :
1---medical castration
2---surgical castration

55. ADT
1--- medical cast. :
*** LHRH ANALOGS/GNRH ANALOGS
a.AGONISTS :LEUPROLIDE&GOSERELIN:
PIT. GNRH AGONIST ACTING BY INTERRUPTING
NORMAL PULSATILE STIMULATION AND
DESENSITISATION OF GNRH RCP, LEADING TO
DOWNREGULATION OF LH AND FSH WHICH
LEADS TO HYPOGONADISM and DRAMATIC
DECREASE IN ESTRADIOL (F.) & TESTOS. (M.)

56. ADT
b. ANTAGONISTS
--- ABARELIX
--- DEGARELIX
--- ABIRATERONE (ZYTIGA): Drugs such as LHRH
agonists can stop the testicles from making
androgens, but other cells in the body,
including prostate cancer cells themselves, can
still make small amounts, which may fuel
cancer growth. Abiraterone blocks an enzyme
called CYP17, which helps stop these cells
from making certain hormones, including
androgens.

57. ADT
***ANTIANDROGERN:
---flutamide (euxelin 250mg)1×3
---bicalutamide (casodex 50mg)1×1
$$$ BOTH ARE ORALNON STEROIDAL AA WHERE
THEY COMPETE TESTOSTERONE AND ITS
POWERFUL METABOLITE DHT FOR THE
AND.RCP. PREVENT THEM FROM
STIMULATION THE GROWTH OF PROSTATE
CANCER CELLS

58. ADT
***OTHERS:
--- PROGESTIN (MEGESTROL)
--- AND. SYNTHESIS INHIBITORS
(KETOCONAZOLE)
--- CORTICOSTEROIDS

59. ADT
2. SURGICAL CASTRATION
$$$ ORCHIECTOMY: RAPID FALL IN
TESTOSTERONE LEVEL AND ITS IRREVERSIBLE.
+++ USED FOR ADVANCED DISEASE
PARTICULARLY IN NON COMPLIANT PT., OR IN
PT WHO NEEDS EMERGENCY BLOCKADE FOR
SPINAL CORD COMPRESSION

60. ADT
@@@ TESTOSTERONE FLARE SYNDROME:LHRH
agonists cause what is known as a “flare”
reaction because of an initial transient rise in
testosterone over the first three weeks after
the shot is given. This can result in a variety of
symptoms, ranging from bone pain to urinary
frequency or difficulty plus spinal cord
compression

61. ADT
• SIDE EFFECTS:Orchiectomy, LHRH analogs, and
LHRH antagonists can all cause similar side
effects due to changes in the levels of hormones
such as testosterone and estrogen. These side
effects can include:
• Reduced or absent libido (sexual desire)
• Impotence (erectile dysfunction)
• Shrinking of testicles and penis

62. ADT
• Breast tenderness and growth of breast tissue
• Osteoporosis (bone thinning), which can lead
to broken bones
• Anemia (low red blood cell counts)
• Decreased mental sharpness
• Loss of muscle mass
• Weight gain
• Fatigue
• Increased cholesterol
• Depression

63. TREATMENT OPTIONS
3. CHEMOTHERAPY:MAINLY RESERVED FOR
CRPC PATIENTS.
--- RGIMENS
A. Docetaxel +prednisolone
B. Mitoxantrone + prednisolone
C. Cabazitaxel+prednisolone
D. Vinorelbine

64. TREATMENT OPTIONS
4. Immunotherapy:
---Sipuleucel-T (provenge:autologus dendritic
cell vaccine).
×××Used for crpc with these criteria :
### good pf (ECOG 0-1)
### estimated life expectancy > 6mo
### no hepatic mets
### no or minimal symptoms

65. TREATMENT OPTIONS
5. Other agents : denosumab and zolendronic
acid
### Used in crpc who have bone mets to prevent
skeletal complications
### must pay attention to creatinine clearance
and calcium level
### S/E: OSTEONECROSIS ESPECIALLY WITH PT
WHO HAVE TOOTH EXTRACTION, poor dental
hygiene or dental appliances