Anatomy, pathology an staging work up of prostate cancer , importance of PSA score, gleason score, prostate cancer

1. Anat omy, Pat hology and st aging work up of
Prost at e Cancer
By Dr Anil Gupta
Moderator Dr Bhavana Rai

2. Anat omy
penis
Seminal
vesicle
Prostate
gland
scrotum
testis
urethra
Sperm
duct

3. bladder
Corpus
cavernosum
Corpus
spongiosum

4. Prost at e
● It is accessory gland of male
reproductive system
● In female represented by
periuretheral glands of skene
● Walnut shaped
● Weighs around 40 gram
● Gross anatomy
Apex
Base
Anterior surface
Posterior surface
Inferolateral surface
Base
Apex
Inferolateral

5. ● Covered by two layer
1) true capsule
- attached to prostate
- outside spread ECE→
2) false capsule
● Clinical importance

6. Relations
Superior
Inferior
Lateral
s

7. Relations
Anterior
Posterior

8. Cross Sectional
Anatomy

9. Anat omy of Uret hera

10. Blood Supply
Arterial supply
● Three main arteries:-
internal pudendal, inferior
vesical and middle rectal
arteries
● Clinical importance:- blood
loss during RP

11. Venous blood supply
Prostatic venous plexus lies
between the true and false
capsule
Deep dorsal vein of penis +
vesical veins
Vesico-prostatic plexus
Internal vertebral venous
plexus
BATESON'S
PLEXUS
( valveless)

12. Nerve Supply
● Controls urine flow
● Secretions discharged
after stimulation of S and
PS
● Radical prostectomy can
lead to erectile
dysfunction
● Nerve sparing radical
prostatectomy

13. Lymphatic drainage
● Regional lymph nodes
- Are nodes of true
pelvis( below bifurcation of
common iliac arteries)
-Pelvic, NOS
- Hypogastric
-Obturator
-Iliac (internal, externa)
- Sacral (lateral, presacral)

14. Met ast asis
● Osteoblastic bony mets (most common)
● Lung
● liver
● Distant lymph node
-Lie outside the confines of the true pelvis.
- Para-Aortic
-Common iliac
-Inguinal, deep & Superficial
-Supraclavicular
- Cervical
-Scalene
-Retroperitoneal, NOS

15. Lobar Classif icat ion
The prostatic urethra and theThe prostatic urethra and the
ejaculatory ducts divide prostateejaculatory ducts divide prostate
into 5 different lobesinto 5 different lobes
Anterior lobe:Anterior lobe:
-Anterior to urethra-Anterior to urethra
-Devoid of glandular tissue-Devoid of glandular tissue
Median or Middle lobe:Median or Middle lobe:
-Between urethra and ejaculatory-Between urethra and ejaculatory
ductsducts
-upper part is related to the-upper part is related to the
bladder trigonebladder trigone

16. Lateral lobes:
-Separated from each other
by prostatic urethra
-Continuous posteriorly
Posterior lobe:
-Posterior to urethra and
Below the ejaculatory ducts
-Palpable during DRE
1- Posterior lobe
2- Lateral lobe
3- Median lobe
4- Anterior lobe

17. Zone Classif icat ion
➢ Peripheral zone(PZ)-
-70% of glandular prostate
-most carcinomas arise from it
➢ Central zone:-
- 25% of the glandular prostate
➢ Transitional zone(TZ):-
-5% of glandular prostate
- BPH arises
➢ Anterior fibromuscular stroma :

18. ● Has three components;-
fibrous, muscular,
glandular
● lined by simple
columnar or
pseudostratified
epithelium
-neuroendocrine cells
-basal/stem cells

19. Size of t he gland
● Size changes with age.
● Grows rapidly during puberty, androgens in the body.
● A typical prostate is about 3 cm thick and 4 cm wide and
weighs about 20 grams,
● It can be much larger in older men.

20. Variat ion wit h age
Young age Old age

21. Fontwork WHAT

23. Funct ions
● It produces a thick, clear fluid that makes the semen more
fluid and protects and nourishes sperm cells in the semen.
● It also plays a part in controlling the flow of urine
● Prevents urine flow during ejaculation
● Secrete a watery mixture of prostate-specific antigen (PSA),
prostatic acid phosphatase, fibrinolysin, and amylase into the
prostatic sinuses

24. Diseases of Prost at e
● Prostatitis
● Benign Prostate Hypertrophy(BPH)
● Prostate Cancer
Prostatic cancer 18%
Prostatitis 2%
BPH 80%

25. CA PROSTATE

26. I nt roduct ion
● The number of new cases of prostate cancer was 129.4 per
100,000 men per year. The number of deaths is 20.7 per
100,000 men per year.
● Approximately 14.0 percent of men will be diagnosed with
prostate cancer at some point during their lifetime
● The highest rates of prostate cancer are in Scandinavia, where
it is the leading cause of male cancer death
● Histological cancers, found during autopsy are even more

29. Due to change in screening recommendations

30. ● Prostate is the second leading site of cancer among males in
large Indian cities like Delhi, Kolkatta, Pune
● Among the top ten leading sites of cancers in India
● 8th MC in men in India
● The incidence is increasing . Data shows that the number of
cases will become doubled by 2020
I ndia Scenario

32. In PGI Chandigarh
● Out of 10019 male diagnosed with cancer 251 are
prostate cancer(2.5%)
● 84.6% were adenocarcinoma
(ICMR 2011-2013)

33. Cause of rise of incidence
● Increase in life expectancy
● Adoption of newer lifestyles
● Screening using prostate specific antigen
(PSA)

34. Risk Fact ors
● Age: Increases with age
●
EthnicityEthnicity: More in African Black men
● Family history: Increases risk
● Number of affected relatives increases the relative risk, notably
if the cancer is found in younger relatives
● Genetic alterations: These six prostate cancer susceptibility
genes identified RNASEL, ELAC2, MSR1, AR, CYP17,
SRD5A2
BRCA1, BRCA2, HNPCC, HPC1
● Obesity: A/W aggressive prostatic cancer

35. Decreased risk
● Low fat diet
● Regular exercise
● Maintenance of normal BMI
● Prophylactic Dutasteride (5a reductase inhibhitor)- REDUCE
trial
- reduced risk of low grade cancer
- increased risk of high grade cancer
Not approved by FDA for chemoprevention

36. No role
● Vitamin E and Selenium, alone or in combination failed to
reduce incidence (SELECT) trial
● Vitamin D and Calcium ingestion did not show any effect
incidence and mortality
● Alcohol use, blood group, body hair distribution, sexual
activity, urban versus rural, and vasectomy do not affect risk
● Benign prostatic conditions
● No viral origin has been found

37. Pathogenesis
Prolonged exposure to testosterone and DHT

38. Progression

39. Prost at ic I nt raepit helial Neoplasia
● Defined as nuclear atypia and architectural derangement without
compromise of the basement membrane.
Low Grade
- minimal atypia
High Grade
- large nucleus with
variation in size,
prominent nucleoli
CA PROSTATE

40. Hist ologic sub t ype
● Acinar adenocarcinoma 9 out of 10
● Remaining 1 out of 10
-Ductal adenocarcinoma
-Transitional cell (or urothelial) cancer
-Squamous cell cancer
-Neuroendcrine carcinoma
-Small cell cancer
-Sarcomas and sarcomatoid cancers

41. Sympt oms
● Early prostate cancer is asymptomatic
(found incidentally or during autopsy)
● Advanced disease symptoms include
- bladder outlet obstruction
- pelvic pain and haematuria
- bone pain, malaise, anaemia or pancytopenia
- renal failure
- may be asymptomatic

42. Diagnost ic Work up

43. PSA
● Is a glycoprotein enzyme secreted into the seminal fluid
by the epithelial cells of prostate gland
● Found in blood in minute quantity
● Well established tumor marker that aids the diagnosis,
treatment and follow up of prostate cancer
● PSA era begins from 1986 when it was first commercially
available
● Is organ specific-- not disease specific
● Elevated prostatic injury, infarct, BPH and Ca prostate

44. ● Age specific reference range
40 to 49 yr 2.5 ng/ml
50 to 59 yr 3.5 ng.ml
60 to 69 yr 4.5 ng/ml
70 to 79 yr 6.5 ng/ml
● Normal PSA for all age is taken as 0-4 ng/ml
● PSA >10 suggestive of cancer
● PSA > 35 is almost diagnostic of cancer
● Senstivity 85%
● Specificity 65-70%

45. ● Free PSA:bound PSA- Used if PSA in between 4 to 10
Biopsy should be done if free PSA ≤ 10%
● PSA density- PSA produced per gram of prostate <0.15
ng/ml, if >0.18 biopsy should be done
● PSA velocity – Before diagnosis rate of change of PSA
>0.75 risk of prostate cancer
>2.0 aggressive cancer

46. PSA in follow up
● Onset of PSA rise- ≤12 months more chances of
metastasis
● PSA doubling time- ≤ 12 months more chances of
metastasis
● PSA failure/ biochemical failure/ treatment failure-
“three consecutive rises in PSA after a nadir, with the date of
failure being the point half way between the nadir date and
the first rise” (earlier)
‘‘an increase of 2 ng/ml or more above the nadir PSA”
(ASTRO)
● PSA bounce- Transient increase in PSA of 0.1 to 0.5
ng/ml or 15% PSA from pretreatment after
Brachytherapy or EBRT---> mean time 18 months

47. Digit al Rect al Examinat ion
● Position -->sim's lateral
position/ modified lithotomy/
knee chest/ standing up
● Characteristics
-anal tone
- size
- shape
- surface
- consistency
- mobility
- Discrete nodule
- pain and tenderness
Prostate
cancer
DRE

48. Typical finding ca prostate-
Hard, nodular, asymmetrical
may or may not be raised
above the surface of gland and
is surrounded by compressible
prostatic tissue
May be normal
Senstivity 70%
Specificity 50%
Only 25-50% with abnormal
DRE have cancer
DRE + PSA - 87%
SDRE

49. TRUS guided biopsy
● Patient preparation
● Done under local
infiltration anaesthesia
● In left lateral decubtits/
lithotomy position

50. SEXTANT
BIOPSY:
• one core, bilaterally,
each from base, mid,
and apex.
• samples both PZ &
TZ.
EXTENDED CORE
BIOPSY SCHEMES

51. Complications
Often
● Hematuria (14 to 50%)
● Hematospermia (10 to 70%)
● Rectal bleeding
Sometimes
● Infection
Rarely
● Epididymitis
● Urinary incontinence
● hospitalization
● Confirmation of diagnosis
● OPD procedure
● Very less pain

52. Diagnost ic t riad f or early det ect ion

53. STAGING WORKUP

54. St aging work up
● Baseline work up
Haemogram/LFT/KFT/CXR
● Essential work up
PSA/Biopsy/Gleason scoring
● Complimentary work up
CT/MRI(becomes essential in higher clinical stage)
PET CT
Bone Scan( essential if bone mets suspected)
Molecular testing

55. Gleason Score
● Scoring on the basis of differentiation of
adenocarcinomas of prostate
● Done by Pathologist on H & E stained microsopic slides
● Done by calculating two pattern in a slide
● Each pattern is given score of 1 to 5 based on
differentiation
● Primary grade -Largest area covering the pattern is
Secondary grade- The highest grade
● Lowest score is 2 and highest is 10
● One of the strongest factor for invasiveness and
metastatic potential

56. ● Gleason grade 1
● Single, separate, closely
packed, uniform round
glands arranged in a
circumscribed nodule with
pushing borders

57. ● Gleason grade 2
● Like grade 1 but more
variability in gland shape and
more stroma separating
glands, such that glands are
separated by less than one
gland's width
● Less circumscribed at
periphery, although no
infiltration into stroma or
between benign glands

58. ● Gleason grade 3
● Single, separate, much more
variable glands
● Well formed, relatively
uniform glands infiltrating
between benign glands;
glands may be angulated or
compressed, separated by > 1
gland diameter

59. ● Gleason grade 4
● Patterns of Gleason grade 4 prostatic
adenocarcinoma:
● (a) Most common is small acinar structures,
some with well formed lumina, fusing into
cords or chains.
● (b) Papillary or cribriform tumors with
irregular / invasive edges

60. ● Grade 5: two patterns
● 5a: Comedocarcinoma: papillary /
cribriform carcinomas with central
necrosis .
● 5b: Single-celled cancer, possibly
forming cords, possibly with vacuoles
(signet ring cells) but without
formation of a glandular lumen.
● Predicts higher rates of metastasis and
death

63. Current perspect ive of gleason
grading
● Score 6 or lower- watchful waiting
score 7 – critical decision making
score 8 or more- definitive therapy
● Rare use of assigning grade 1 or 2 in biopsy
● Gleason Index:- radical prostatectomy specimens with
multifocal disease, consisting of a dominant tumor referred to
as an index tumor, gleason score of index tumor is considered.

64. CT SCAN
●
Primary role
●
Size determination of the gland
●
Assess pelvic LN metastasis
●
Treatment planning in RT
●
EPE:
– Loss of periprostatic fat planes
– Bladder base deformity
– Obliteration of the normal angle b/w the SV and post. aspect of UB
●
LN involvement
– Abnormality in size
– Sensitivity 25%
– Reserved for patients with higher PSA values (>20-25 ng/ml)
– CT guided FNAC

65. ●
Limitation of CT
●
Lacks the soft tissue resolution needed to detect intraprostatic anatomic
changes due to primary tumor , capsular extension or SVI because the
neoplasm usually has the same attenuation as the normal prostate gland
●
Can't detect microscopic disease
●
False Positive- Artifact of Bx and plane b/w SV and UB base may be
obscured by rectal distension

66. MRI
●
Superior to CT in defining prostate apex, NVB and anterior rectal wall
●
Better delineation of periprostatic fat involvement
●
T1w- provides high contrast b/w water density
structures i.e. Prostate, SV and fat, NVB, perivesical
tissue and LNs
●
T2w fast spine echo- zonal anatomy, architecture of
SV
●
Ca Prostate: A focal, peripheral region of decreased signal intensity
surrounded by a normal(high intensity) peripheral zone
●
BHP: centrally located nodules of similar signal
●
Primary staging sensitivity- 69%
●
Endorectal surface coil MRI- accuracy of 54-72% staging the primary
and detects SVI and ECE

68. MRI for screening
Still in development phase
PIRADS 1 – Very low (clinically significant cancer is highly unlikely to be
present)
PIRADS 2 – Low (clinically significant cancer is unlikely to be present)
PIRADS 3 – Intermediate (the presence of clinically significant cancer is
equivocal)
PIRADS 4 – High (clinically significant cancer is likely to be present)
PIRADS 5 – Very high (clinically significant cancer is highly likely to be
present)

69. PET Scan
● Used in the assessment of
metastases, detect
intraprostatic cancer.
● PRINCIPLE:- measures
radiation from radioactive
atoms incorporated into
radiotracers that preferentially
accumulate at sites of tumor
● FDG PET is most commonly
used
● 18F-fluorocholine:-
- has higher uptake in cancer
sites
- less accumulation in the
bladder
- can differentiate with BPH

70. Mult iple
imaging
modalit ies
showing
prost at e
cancer

71. 99
Tc BONE SCAN
●
Clinically apparent metastatic disease limited to bone in 80-85%
of patients of metastatic ca prostate
●
A close correlation exists between pretreatment PSA level and
incidence of abnormal bone scan results
●
Osteoblastic secondaries
●
MC sites of metastasis
●
Vertebral column- 74%
●
Ribs- 70%
●
Pelvis- 60%
●
Femoral- 44%
●
Shoulder girdle-41%

72. STAGI NG

73. ●
AJCC 7th
edition staging is used
● Minimum work up required
- DRE
- Biopsy
- PSA
- CT/MRI/Bone scan- if higher clinical stage, gleason
score, bony pain
● For pathological classification:- total prostatectomy
including regional lymph node dissection with full
histologic evaluation

74. T – Pr imar y t umor
● TX – Primary tumor cannot be
assessed
● T0 – No evidence of primary tumor
● T1 – Clinically inapparent tumor not
palpable or visible by imaging
● T1a – Tumor incidental histologic
finding in 5% or less of tissue
resected
● T1b – Tumor incidental histologic
finding in greater than 5% of tissue
resected
● T1c – Tumor identified by needle
biopsy (due to elevated prostate-
specific antigen [PSA] level); tumors
found in 1 or both lobes by needle
biopsy but not palpable or reliably
visible by imaging

75. ●T3 – Tumor extending through the
prostatic capsule; no invasion into the
prostatic apex or into, but not beyond, the
prostatic capsule
●T3a – Extracapsular extension (unilateral
or bilateral)
●T3b – Tumor invading seminal vesicle(s)
● T2 – Tumor confined within prostate
● T2a – Tumor involving less than half a lobe
● T2b – Tumor involving 1 lobe or less
● T2c – Tumor involving both lobes

76. ● T4 – Tumor fixed or invading
adjacent structures other than
seminal vesicles (eg, bladder
neck, external sphincter,
rectum, levator muscles, pelvic
wall)

77. Pat hological T st age
pT2 Organ confined
pT2a- Unilateral, one-half of one side or less
pT2b -Unilateral, involving more than one-half of side but
not both sides
pT2c -Bilateral disease
pT3- Extraprostatic extension
pT3a- Extraprostatic extension or microscopic invasion
of bladder neck**
pT3b- Seminal vesicle invasion
pT4- Invasion
Resection margins should be mentioned
There is no pT1

78. N St age – Lymph Nodes
● NX – Regional lymph
nodes (cannot be
assessed)
● N0 – No regional lymph
node metastasis
● N1 – Metastasis in
regional lymph node or
nodes
Pathological N stage is same

79. M st age- Met ast asis
● PM1c – More than 1 site of
metastasis present
● MX – Distant metastasis
cannot be assessed
● M0 – No distant metastasis
● M1 – Distant metastasis
● M1a – Non regional lymph
node(s)
● M1b – Bone(s)
● M1c – Other site(s)

80. Composit e St aging

82. RI SK STRATI FI CATI ON

83. D' amico Risk St rat if icat ion
● First one to give concept
● Predicts about chances of
recurrence after treatment
● Low risk- T1-T2a and GS
≤6 and PSA ≤10
● Intermediate risk- T2b
and/or GS =7 and/or PSA
>10–20
● High risk- ≥T2c or PSA
>20 or GS 8–10
● Does not take into
account other parameters

84. ● Uses Gleason score, serum PSA, and clinical
stage – to predict whether the tumor will be
confined to the prostate

85. The UCSF-CAPRA score
● UCSF developed the Cancer
of the Prostate Risk
Assessment score
● 0-2 low risk
3-5 intermediate risk
6-10 high risk

86. NCCN Risk cat egories

87. SCREENI NG

88. Screening
● The primary endpoint of screening:-
➢ The goal is not to detect more carcinomas, but reduction
in mortality from Pca.
➢ Improving the quality of life (QALY)
Done by checking serum PSA
- if >4.1, biopsy is done

89. AUA recommendations for screening
● No screening <40 yr
● No routine screening for average risk between 40 to 54 yr,
only for high risk
● Routine screening from 55 to 69 yr with shared decision
making
● 2 yr gap in between
● No screening for any man with life expectancy < 10yrs
● No screening >70yr

90. I s Screening really needed?
Out of 1000 screening (age 55-69)
210-230 would undergo
biopsy
100-120 negative
(1/3rd
will develop biopsy
related complication)
110 positive
(50 would develop
treatment related
complication, 1
would die)
0-1 death would be avoided

91. ● Harms
- unnecessary biopsies
- complications of biopsy
- overtreatment
- psychological
- needs huge investment from government
● Benefits
- Early detection and diagnosis
- incidence of metastatic disease at presentation declined
● US Preventative Service Task Force's does not
recommend prostate cancer screening

92. Conclusion
● CA Prostate is cancer of elderly
● It is slow growing, many remains latent for years
● Incidence rising
● Screening still controversial
● Diagnostic Triad: - PSA, DRE, TRUS guided biopsy
● Gleason score and PSA is taken into account for staging
by AJCC
● Management depends on stage, Risk Stratification, Life
expectancy, patient's preference and availabilty
● “Patient does not die due to prostate cancer ,they die
with it”

93. Thank you.... :)