carcinoma prostate from anatomy to management

1. Dr. Ayush Garg

2. Anatomy Of Prostate
• The prostate is a walnut-sized gland located in
front of the rectum and below the bladder.
• It surrounds the urethra, the tube-like channel
that carries urine and semen through the
penis.
• The primary function of the prostate is to
produce seminal fluid, the liquid in semen that
protects, supports, and helps transport sperm.

3. Base of the Prostate
The base is directed
upward near the
inferior surface of the
bladder. The greater
part of this surface is
directly continuous
with the bladder wall.
Apex of the Prostate
The apex is directed downward
and is in contact with the superior
fascia of the urogenital diaphragm.
Anatomy Of Prostate

4. Anatomy Of Prostate
• Blood supply
– Inferior vesical artery
• Derived from the internal iliac artery
• Supplies blood to the base of the bladder and prostate
• Capsular branches of the inferior vesical artery
– Help identify the pelvic plexus
• Nerve supply
– Neurovascular bundle
• Lies on either side of the prostate on the rectum
– Derived from the pelvic plexus , arising from the S2-4 and
T10-12 nerve roots
– Important for erectile function.

5. Prostatic Zonal Anatomy
• There are four zones
of the prostate :
 the peripheral zone
(PZ) ,
 transition zone (TZ) ,
 Central zone, and
 anterior fibromuscular
stroma zone.

6. • Peripheral zone (PZ)
– 70% of cancers
• Transitional zone (TZ)
– 20%
• TZ prostate cancers are
relatively nonaggressive
• PZ cancers are more
aggressive
– Tend to invade the peri-
prostatic tissues.

7. Lymphatic Drainage

8. Regional Lymph Nodes
• Pelvic
• Hypogastric
• Obturator
• Iliac (internal, external)
• Sacral (lateral, presacral, promontory
[Gerota's])

9. Metastatic Lymph Nodes
• Distant lymph nodes lie outside the confines of the
true pelvis.
• The distant lymph nodes include the following:
• Aortic (paraaortic lumbar)
• Common iliac
• Inguinal, deep
• Superficial inguinal (femoral)
• Supraclavicular
• Cervical
• Scalene
• Retroperitoneal

10. Epidemiology
 Second leading cause of cancer death in men from western
countries
 It is one of the 10 leading cancer sites in males in India,
accounting for about 4 % all male cancers
Age-adjusted annual incidence 176 per 100,000 in USA, whereas
only 7.1 in Mumbai and 4.3 in Bangalore (NCRP 1990-96)

11. Etiology
• Family history: 2-3 fold increased risk in men with a first
degree relative.
• Hereditary association: Early onset of disease and a
Mendelian autosomal dominant inheritance– accounting for
<10% of all cases but 40% in younger men in <55 years.
• Racial Factors: Striking differences in incidence and mortality
between the Black and White population, more common in
blacks.
• Environmental Factors: also responsible for ethnic differences,
as Asians migrating to USA have higher incidence of prostate
cancer.

12. Etiology
• Diet: one of the most important modifiable risk factors -- high
fat intake increases risk whereas diets rich in carotenoids
(tomato based products containing lycopene) and vitamin-E
are protective.
• No association with cigarette smoking, alcohol use, height
and weight and blood group.
• No data regarding viral origin.
• No convincing evidence that Vasectomy increases risk of
prostate cancer

13. Pathology
• Adenocarcinoma
– 95% of prostate cancers
• Developing in the acini of prostatic ducts
• Rare histopathologic types of prostate carcinoma
– Occur in approximately 5% of patients
– Include
• Small cell carcinoma
• Mucinous carcinoma
• Endometrioid cancer (prostatic ductal carcinoma)
• Transitional cell cancer
• Squamous cell carcinoma
• Basal cell carcinoma
• Adenoid cystic carcinoma (basaloid)
• Signet-ring cell carcinoma
• Neuroendocrine cancer

14. CLINICAL MANIFESTATIONS
• EARLY STAGE
• Asymptomatic
• Cancer is in the peripheral
zone
• LOCALLY ADVANCED DISEASE
• Obstructive / irritative
voiding
 Hesitancy
 Intermittent urinary stream
 Decreased force of stream
--- May have growth into
the urethra or bladder
neck
• Retention of urine
• Hematuria
• Hematospermia
• Renal failure
• Pelvic pain
• ADVANCED DISEASE (spread
to the regional pelvic lymph
nodes)
• Edema of the lower
extremities
• Pelvic and perineal
discomfort
• METASTATIC DISEASE
• Bone pain
• Spinal cord
compression symptoms
• Paraperesis

15. • Hematuria- prostatic urethra/ trigone involvement
• Hematospermia
• Extra prostatic spread- often asymptomatic/ extensive dis.
• Rectal involvement-
• Hematochezia
• Constipation
• Intermittent diarrhoea
• Abdomino-pelvic pain
• Renal impairment due to prolonged bladder outlet obstruction.
• Fluid retention/ electrolyte imbalance

16. • Involvement of neurovascular bundles/ GUD:
------- Impotence/ pelvic pain/ priapism
• Advanced disease- metastatic symptoms
– Bony- pain / pathological fracture/ Spinal tenderness
– Spinal cord compression- neurological deficits/ sensory-
motor changes/ bladder-bowel dysfunction
– Pelvic / Para aortic LAP- edema of abdominal wall,
genitalia or lower extremities/ mass abdomen
– Adrenal/ lung/ skin metastasis.
– PNS- SIADH/ Cushing syndrome.

17. STAGING OF PROSTATE CANCER

20. DIAGNOSTIC WORK-UP
• Laboratory
– Complete blood cell count, blood biochemistry
– Serum PSA (total, free, percentage free)
– Plasma acid phosphatases (prostatic/total)
• Radiographic imaging
– Transrectal ultrasonography (for biopsy guidance)
– Biopsy/Needle biopsy of prostate (transrectal,
transperineal)
– Chest radiograph (high risk for metastatic disease)
– Computed tomography of pelvis.
– Radioisotope bone scan
– Magnetic resonance imaging.
– PET CT Scan for metastasis in high risk cases

21. Diagnosis
• Signs and symptoms of Prostatism
• Abnormal DRE: although correlates poorly with the
volume and extent of cancer, an integral part of the
algorithm.
• Serum PSA: usually > 4 ng/ml
With increasing PSA level, chance of getting cancer
increases, but less likely to be organ confined.
• TRUS guided Biopsy:
1) to establish the diagnosis.
2) to report extent and grade of cancer in each core.
3) to document presence of PNI or ECE.

22. The Number of Cores Removed
• In 1990s 6 core biopsy was done but now 12 core biopsy is
done.
• Many different theories exist as to the “best” way to “sample”
the prostate so as to find any cancer that may be present.
• There are no “absolute” prostate biopsy guidelines.
• Cores from all major regions of the prostate so as to ensure
complete “geographic” coverage is done.
• Cores from any region of the prostate that felt suspicious
under DRE or TRUS is done.
• Biopsy sites included the
1. midlobe parasagittal plane
at the apex,
2. the midgland, and
3. the base bilaterally.

23. LABORATORY INVESTIGATIONS
• PROSTATE SPECIFIC ANTIGEN
– Serine protease glycoprotein secreted by prostatic epithelium
– Carcinoma specific
– Normal : 0.4 - 4 ng/ml (upper limit 2.6 ng/ml)
– t1/2 : 2.2― 3.2 ±0.1 days
– Mild elevation 4 ― 10 ng/ml
– Significant elevation >10 ng/ml
– Sensitivity ― 85%
– Specificity – 65-70%
– Estimated rate of cancer detection by PSA screening ― 1.8-
3.3%
– Carcinoma with normal PSA ― 25%

24. • Age specific PSA :
– Age PSA
40-50 0-2.5
60-70 0-4.5
70-80 0-6.5
• Pretreatment serum PSA is also predictive of EPE and
SVI :
PSA Rate of organ-confined disease
– 4 -10 ng/ml 53% - 70%
10 -20 ng/ml 31% - 56%
• Roach’s Probability of ECE, SVI and LNI:
– ECE+ = 3/2×PSA +(GS-3)×10
– SVI+ = PSA +(GS-6)×10
– LNI+ = 2/3×PSA +(GS-6)×10

25. Digital Rectal Examination
• Cornerstone of the physical examination/ instrumental in staging
• Sim’s lateral position.
– Organ palpation:
• Craniocaudal and transverse dimension
• Consistency / Mobility
• Any firm/ elevated area and its size.
• 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.
– Prostatic induration - BHP nodule/ calculi/ infection/
granulomatous prostatitis / infarction
– Specificity- 50% and Sensitivity- 70%
– Only 25-50% of men with an abnormal DRE have cancer.
– DRE + PSA specificity 87%

26. Prostate Anatomy on DRE

27. TRANRECTAL ULTRASONOGRAPHY(trus)
• TRUS of the prostate, first described by Wantanabe (1968)
• TRUS-guided systematic sextant biopsy protocol by Hodge
• Normal adult prostate : Symmetric, triangular, relatively homogenous structure
with an echogenic capsule
The mature average prostate is between 20 and 25 g and remains relatively constant until about age 50, when the gland enlarges in many men
( Griffiths, 1996 )
The paired seminal vesicles are positioned posteriorly at the base of the prostate.
They have a smooth, saccular appearance and should be symmetrical. Normal SV
measures 4.5 to 5.5 cm(l) and 2 cm (w)

28. • Extraprostatic extension
– Sensitivity-66% Specificity- 46% Accuracy- 58%
• Seminal vesicle invasion
– Echogenic abnormalities
– Ant. displacement and enlargement of SV

29. – TRUS-directed prostate needle biopsy remains the gold
standard for diagnosis of prostate cancer
– Guided biopsy of the prostate
• Recommendation: TRUS guided Bx in patients with PSA> 4 ng/ml
• To establish the diagnosis
• To report extent and grade of each core
• To document presence of Pelvic LN involvement and ECE
– Staging of clinically localized prostate cancer
– Guidance during the seed/interstitial brachytherapy
– Monitoring prostate cryotherapy
– Evaluation and aspiration of prostate abscess
– Monitoring the response to prostate cancer treatment

30. Gleason’s Score
• Donald F. Gleason in 1966 created a unique
grading system for prostatic carcinoma based
solely on the architectural pattern of the
tumor.

32. Gleason’s Score
• Prostate cancer has a pronounced morphological
heterogeneity and usually more than one histological
pattern is present.
• The primary and secondary pattern, i.e. the most
prevalent and the second most prevalent pattern are
added to obtain a Gleason score or sum.
• It is recommended that the primary and secondary
pattern as well as the score be reported, e.g. Gleason
score 3+4=7.
• If the tumour only has one pattern, Gleason score is
obtained by doubling that pattern, e.g. Gleason score
3+3=6.

33. Grades
• Primary grade - assigned to the dominant pattern of
the tumor (has to be greater than 50% of the total
pattern seen).
• Secondary grade - assigned to the next-most
frequent pattern (has to be less than 50%, but at
least 5%, of the pattern of the total cancer observed)
• Gleason Score= Predominant pattern (1-5) +
Secondary pattern (1-5)
• Best Score=2, Worst Score=10

36. IMAGING
• CXR
– Pulmonary metastasis
– Miliary pattern
• Axial skeletal survey : Specific sites of bony pain
– Osteoblastic secondaries
• USG abdomen-pelvis:
 hydroureteronephrosis
 large post void residual urine volume
 retroperitoneal lymphadenopathy
 Liver mets.

37. CT SCAN
• Primary role
– Size determination of the gland
– Assess pelvic LN metastasis
– Treatment planning in RT
– Extra Prostatic Extension:
• 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

38. • Limitation of CT
– Lacks the soft tissue resolution needed to detect intraprotatic 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

39. 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

40. • Indications: High likelihood of capsular invasion and LN metastasis
– Abnormal DRE
– PSA>20
– Poorly differentiated ca
• Sensitivity to locate gland tumor- 79% and specificity- 55%
• LN detection- Low sensitivity but high specificity

41. MRSI (Magnetic Resonance Spectroscopic Imaging)
– Improved diagnostic accuracy of MRI both in localizing and staging and risk-
stratifying patients
– Specificity for tumor location (MRI + MRSI) ~ 91%.
– Accurate localization of prostate tumors and improved guided biopsy
– Combined MRI/MRSI enhances the assessment of both ECE and SVI and
capsular breech
– Predict tumor aggressiveness
– Distinguishing b/w tumor and post biopsy hemorrhage
– Detect residual cancer following t/t and follow-up
– Development of more focused therapy

42. 99Tc BONE SCAN
• Clinically apparent metastatic disease limited to bone in 80-85%
of patients of metastatic ca prostate
• Osteoblastic secondaries
• MC sites of metastasis
– Vertebral column- 74%
– Ribs- 70%
– Pelvis- 60%
– Femora- 44%
– Shoulder girdle-41%
Indications: Pretherapy
– Early stage disease-T1-T2 with
• PSA > 20 ng / ml
• GS≥ 8
• Bony pain
– T3-T4 –Symptomatic patients
– High grade tumor
– Base line: Elderly, patients with h/o arthritis, to document degenerative
changes that may later be interpreted as metastatic osseous disease and to
assess t/t effectiveness

43. What is a Prostate-Specific
Membrane Antigen (PSMA) study?
• PSMA studies are performed on newly diagnosed prostate
cancer patients to determine if the disease has spread to
pelvic lymph nodes.
• The study is also performed on patients who have had their
prostate gland removed and have an increase in prostate-
specific antigen (PSA) blood levels.
• PSMA is a membrane glycoprotein which is overexpressed
manifold on prostate cancers, and the expression increases
with Tumor Aggressiveness,
Androgen-independence,
Metastatic Disease,
Disease recurrence

44. • Ga-68 PSMA PET/CT Imaging identifies tumor cells expressing
PSMA antigen with excellent sensitivity & specificity, thereby
detecting lesions remaining unidentified by conventional
methods.
• The study involves a special molecule called a monoclonal
antibody developed in a laboratory and designed to bind to
the prostate-specific membrane antigen on cancer cells. This
antibody is paired with a radioactive material called
Gadolinium 68 that can be detected by a gamma camera.
When injected into the patient’s bloodstream, the radioactive
antibody travels and attaches to cancer cells.
• The gamma camera then produces three-dimensional images
of the tumor and its location inside the body.

45. Advantages/ Indications:
• PET Imaging with 68Ga-PSMA ligand can present lesions
suspicious for prostate cancer with excellent contrast and a
high detection rate even when the level of prostate specific
antigen is low
• PSMA expression allows the identification of benign and
malignant prostatic epithelium and may be a potentially
valuable marker in the treatment of patients with prostate
cancer
• 68Ga-PSMA PET has promising potential for restaging in
recurrence/ biochemical failure after definitive treatment of
prostate cancer
• PSMA PET could be used as a marker of patient response to
anti-androgen drugs

46. This 73-year-old man was recently diagnosed with prostate
cancer and has an elevated PSA. PET/CT shows the intense
activity in the prostate cancer (arrow) and the spread to the
left pelvic bone (b).

47. Treatment
• Depends on stage, patient's age and GC
• EARLY
• LOCALLY ADVANCED
• METASTATIC
• 3 risk group
Stage Initial PSA GS
– LOW RISK T1 –T2a <10 ng/ml ≤ 6
– INTERMEDIATE RISK Bulky T2b 10- 20 7
– HIGH RISK ≥ T2c >20 8-10
(D'Amico et al)
• Localized disease
– Observation
– Radical radiotherapy
– Radical prostatectomy
– Cryoablation
oLocally advanced disease
•Radical radiotherapy
•Hormonal therapy
oMetastatic disease
•Palliative RT
•Hormonal therapy
STAGE
PSA
GLEASONS SCORE

63. SURGERY

64. RADICALPROSTATECTOMY
Described by young et al. (1905) & popularized
by Jewett
Procedure:
Complete removal of prostate ,surrounding
capsule, seminal vesicle,ampulla, vasdeferens.
 Approaches
 Retropubic
 Transperineal
 Laproscopic
 1.pure
 2. robot assisted-(da
vinci robotic arm)-
• less blood loss
• 10 fold magnification
• three dimensional visualization.
• Watertight anastomosis eases early
removal of catheter.
o Selection:
• clinically localized prostate
ca (cT1-
cT3a,N0/Nx,M0/Mx)
• <60 yrs
• Good GC
• Life expectancy >10yrs
• No life threatening
ancillary disease
E
V
O
L
U
T
I
O
N

65.  WATCHFULWAITING  RADICAL
PROSTATECTOMY
RR 348 (AS) 347 (RP)
0.56 (CI-
0.36-0.88)
DEATH 50 30
0.6 (CI-0.42-
0.86)
METS LOWERRISK
OF
METASTASIS
Cumulative probability of developing metastatic disease
10 yrs after diagnosis 25% in conservatively managed
patients.
Cancer specific mortality 25% in the WWpatients.
Absolute & statistically significant increase in OS at 10
yrs for patients in surgery arm.
SCANDINAVIAN
TRIAL
695 men with
clinically
localized
cancer prostate
RP vs. watchful
waiting with
systematic treatment
deferred until
disease progresses.

66. Patient selection for pelvic lymph node dissection:
o Definitely men with pelvic node involvement fare poorly. So
controversy persists about PND.
o Low risk disease- Pelvic node involvement chance <5%.
o LN dissection: excision of fibrofatty tissue & lymphatic tissue
between bifurcation of common iliac artery superiorly to the
femoral canal inferiorly and to pelvic sidewall laterally.
Posteriorly to obturator nv.
o Extended LN: conventional LN with posteriorly obturator vessels
and iliac vein.
Current practice : to restrict PLND at time of RP to men with a
≥ 2% risk of positive nodes according to a contemporary
nomogram.

68. RADIOTHERAPY
 Adjuvant
 Radical
 Palliative
Techniques:
• Conventional
• 3D CRT
• IMRT & IGRT
• Proton Therapy
• Brachytherapy

69. Adjuvant RT
Indications:
Immediate- after RP with positive Sx margins,
SVI, poorly diff. ca (GS 8-10), LN mets
Delayed- ↑PSA level with no e/o distant mets,
clinically local recurrence and LN mets

70. Localization, Immobilization, and
Simulation
■ Patient preparation: full bladder and empty rectum minimizes dose
to critical
structures (bladder, small bowel, rectum).
■ Patient position: supine, with arms folded on the chest.
■ Immobilization:
■ Consider a body mold such as a vacuum-lock immobilization bag.
■ A knee bolster with the feet banded together provides a comfortable
and
reproducible position.
■ Simulation: CT scan from midabdomen to midfemur.
■ CT should include the L4-L5 intervertebral disk level superiorly to
below
the lesser trochanters inferiorly.

71. Conventonal
• For historical purposes, with conventional technique,
pelvic irradiation is usually treated with a four-field
box. The target volume usually includes the prostate,
seminal vesicles, obturator, and proximal internal and
external iliac nodal regions. Occasionally common iliac,
para-aortic, and even perirectal nodes are included in
the initial target.
• With CT planning, the prostate, seminal vesicles,
rectum, small bowel, bladder, pelvic vessels, and penile
bulb may be contoured to facilitate shielding of the
rectum and small bowel.

72. • Field size :
• Superior border-L5-S1
• Inferior border- 1.5-2 cm
distal to junction of
prostatic and
membranous urethra
(lower border of ischial
tuberosity)
• Lateral border- 1.5-2
cm lateral to bony
pelvis
• Common iliac LN treated
by 18X15 cm field
Corner blocks are usually placed at
all four corners to limit dose to the
small bowel and femoral heads.

73. • Anterior margin-0.5 to 1 cm posterior to
projected cortex of PS
• Posterior margin-S2-3 interspace to include the
upper presacral LNs

74. • Boost field
• Superior border extends to the top of
the acetabulum - 3-5 cm above pubis
• Anterior border-1.5 cm posterior to ant.
margin of pubic symphysis
• Posterior border- 2 cm behind the
rectal marker
• Inferior border- short of internal anal
sphincter or caudal to ischial tuberosity
• Laterally to include 2/3 of the obturator
foramen

75. SEQUELAE OF RT
• Conventional:
• Acute – 60% in 3rd week of RT
• Rectal - discomfort, tenesmus, diarrhoea
• Urinary- frequency, urgency, nocturia
• Urinary incontinence (any 0–60%, severe 2–15%)
• Late – 6 months/ later
• Chronic diarrhoea , proctitis, rectal-anal stricture
• Bleeding PR- 3.3%, bowel obst./ perforation- 0.6%
• Fatal complication- 0.2%
• Rectal toxicity is propotional to volume of rectal wall exposed to high dose
(any 2–100%, severe 0–20%)
• Erectile dysfunction (10–85%)

76. Target Volumes
CTV = entire prostate +/- seminal vesicles +/- LN.
■ Low-risk prostate cancer CTV = entire prostate only.
■ Intermediate-risk prostate cancer CTV = prostate + proximal 1 cm
of the bilateral seminal vesicles.
■ High-risk prostate cancer CTV = prostate + proximal 2 cm of the
bilateral seminal vesicles (consider entire seminal vesicles if grossly
involved) +/- LN regions.
■ Definition of the PTV
■ PTV margin depends on the immobilization technique and the
particular IGRT technology being used.
■ With CBCT IGRT, an 8 to 10 mm expansion is used, except
posteriorly, where a 5 to 8 mm margin is used. The PTV expands into
the rectum, whereas the CTV does not.

77. Representative pelvic lymph node clinical target volume (CTV) contours from RTOG
consensus computed tomography.
A, Common iliac and presacral CTV lymph node volumes (L5/S1).
B, External, internal, and presacral CTV lymph node volumes (S1-S3).
C, External and internal Iliac CTV lymph node volumes (below S3).
D, End of external iliac CTV lymph node volumes (at top of femoral head, boney
landmark for the inguinal ligament).
E, Obturator CTV lymph node volumes (above the top of the pubic symphysis).

78. Dose/ Fractionation
Total prescription dose of 75.6 to 79.2 Gy in 1.8 to 2 Gy/fx for low
risk cancers and intermediate or high risk cases doses upto 81 Gy
provide improved PSA assessed disease control.
■ If treating LN prescribe initial 45 to 50.4 Gy/1.8 Gy/fx to the pelvis
(lymph nodes + prostate + seminal vesicles). Grossly positive lymph
nodes can be boosted to a higher dose.
● Boost the seminal vesicles to 54 to 66 Gy, pay attention to small
bowel position and potential for toxicity, and boost the prostate
alone to final prescription dose.

79. LANDMARK TRIALS
RTOG 9413 (2003)
Whole Pelvic RT
followed by Prostate
Boost versus Prostate
Only RT
4 months of Neo
Adjuvant Hormone
Therapy + Concurrent
Hormone Therapy or
4 months of Adjuvant
Hormone Therapy
Result
• Whole Pelvic RT + Neo Adjuvant Hormone arm had
59.6% of 4 years PSA relapse free survival better
than other arms.

80. • The delivery of radiotherapy has changed considerably
since the 1980s.
• For example, the integration of various forms of IGRT
for EBRT and brachytherapy, and delivery with IMRT for
EBRT planning, have enabled accurate dose escalation
to improve outcomes and reduce toxicity.
• Furthermore, radiobiological models have suggested
that prostate cancer cells are more sensitive to doses
delivered in larger fraction sizes than in smaller, more
frequent doses; normal tissues experience less toxicity
with such doses.

81. Target Volume Definition for EBRT:
Post-Prostatectomy
Definition of prostate bed CTV:
■ CTV = prostate bed +/- remnant seminal vesicles.
■ Contour the prostate bed inferiorly to below the urethrogram
beak and continue to the top of the pubic symphysis.
■ Extend the contours laterally to the medial edge of the sacro-
rectogenitopubic fascia bilaterally. Where this fascia is not visible
one may alternately use the medial border of the obturator
internus.
■ Anteriorly include the bladder up to the pubic symphysis with
gradual reduction posteriorly and superiorly to the bladder for 1
to 2 cm above the pubic symphysis.
■ Include at least 1 cm of the posterior bladder in the CTV.
Extend more superiorly for patients with pathological
involvement of the prostate base

82. ■ Include surgical clips around the prostate bed. Do not include
hemostasis clips higher in the pelvis if the seminal vesicles are
uninvolved.
■ Definition of the PTV.
■ PTV = 7 to 10 mm around the CTV. Posteriorly toward the
rectum, the margin may be reduced to 5 mm.
■ Tighter margins may be used with more advanced IGRT and
immobilization.
Dose/Fractionation
■ Doses of 64.8 to 70.2 Gy in 1.8 to 2 Gy per fx are used
postoperatively.
■ A distinction can be made between adjuvant (absence of
detectable disease) and salvage (presence of detectable disease)
as follows:
■ 64 to 66 Gy for adjuvant therapy

83. IMRT
GTV adenocarcinoma of the prostate is not visualized well and therefore is
not contoured separately.
TARGET LOW RISK INTERMEDIATE RISK HIG RISK
CTV1 PROSTAE +/-
PROXIMAL
SEMINAL
VESICLES
(74GY)
PROSTATE +PROX.
SEMINAL
VESICLE(76-78GY)
PROSTATE=GROSS ETRACAPSULAR
DISEASE &PROX.SEMINL VESICAL(76-
78GY)
CTV2 -- DISTAL SEMINAL
VESICALS(56 GY)
DISTAL SEMINAL VESICLES AND
LN(56 GY)

84. Prostate Motion
To see:
Interfractional motion: Movement on daily basis.
Intrafractional motion: Movement during treatment.
Is the positional relationship between the prostate and
bony anatomy static?
Interfractional 3D displacement of prostate and bony anatomy
were 5.6 &4.4 prior to localization,2.8 &4.4 mm After post
localization system.---thus bony landmarks is not sufficient for
accurate localization of the gland.
Hence came the role of Fiducial Gold Seed markers with daily
electronic portal imaging

85. Dose Escalation
■ A hypofractionated regimen of 70 Gy/2.5 Gy/fx may be
considered. Other hypofractionated schedules include
70.2 Gy/2.7 Gy/fx,
62 Gy/3.1 Gy/fx (4 fx/week), or
51.6 Gy/4.3 Gy/fx.

86. Dose Escalation in CA Prostate
Phase III randomized trial from MD Anderson
Hospital (2008)
Arms 8 years
Biochemical
Control
PSA Relapse
Free Survival
I 70 Gy
Conventional
63% 64%
II 78 Gy
Conventional
+ 3D Boost
88% 70%
Kuban DA, Tucker SL, Dong L et al (2008) Long-term results of the MD Anderson randomized
dose-escalation trial for prostate cancer. Int J Radiat Oncol Biol Phys 70:67 –74

87. RTOG 94-06
Dose escalation using 3D CRT
5 Sequential Dose Levels 5 years PSA Relapse free
survival
68.4 Gy @ 1.8Gy/# 68%
73.8 Gy @ 1.8Gy/# 73%
79.2 Gy @ 1.8Gy/# 67%
74 Gy @ 2Gy/# 84%
78 Gy @ 2Gy/# 80%
79.2 Gy given in 1.8 Gy/day was the maximally
well-tolerated dose. Toxicities were significantly higher
with 78 Gy given in 2.0 Gy/day than the 79.2 Gy dose level.

88. Dose Escalation using Proton
Porton Radiation Oncology Group 95-09
(2005,2008)
• 393 patients, T1b-T2b and PSA <15, 58% low, 33%
intermediate risk. No ADT
• 70.2 vs 79.2 Gy with proton boost after 50.4 Gy -
photon to P&SV.
• Median follow up 5.5 years.
• 5-year RFS: Low risk: 84→98%
• Intermediate-risk: 79→91%
• No OS diff

89. SBRT
• King et al reported 35-36.2 Gy in 5# resulted
in 5 years relapse free survival of 93% with
decreased rectal and urinary toxicity.
• MSKCC Phase I randomized trial is
undergoing for SBRT using Image Guided
IMRT.
• 5 mm margin around prostate and 3 mm
margin at rectal junction.

92. SEQUELAE OF RT
• 3DCRT/ IMRT
• Acute and late urinary toxicities similar, grade 3
hematuria-0.5%
• Stricture -4% and incontinence- 2% (h/o prior TURP)

93. Brachytherapy
It is also a dose escalation method when
combined with EBRT.
Low Risk Disease: Brachy only
High Risk Disease: EBRT + Brachy

94. • LDR Brachy
• As Brachy only: I125 144 Gy, Pd103 125 Gy.
• After EBRT 40-50 Gy: I125 110 Gy, Pd103 90 Gy.
• Goals LDR Toxicity
• V100: 95-99% Acute Urinary Retention
• V150: <70% Rectal Toxicty
• V200: <20% Erectile Dysfunction
• D90: 90-100%

95. • HDR Brachy
• As Brachy only: 9.5Gy twice daily for 2 days or
10.5Gy in 3# over one day.
• After EBRT: 9.5Gy in 2# over one session.
• Goals
• V100: 90-96%
• V150: <40%
• D90: >90%

96. General Inclusion Criteria:
• Clinical Stage T1-T3b and selectedT4
• Gleason score 2-10
• PSA No upper limit, but in almost all cases, patient doesnot
have documented distant metastasis (TxN0M0)
Exclusion Criteria:
 Relative Contraindications
• Severe urinary obstructive symptoms
• Extensive TURP defect or TURP within 6 month
• Collagen vascular disease
 Absolute Contraindications
• Unable to undergo anesthesia (general, spinal, epidural, or local)
• Unable to lay flat

97. IODINE125 PALLADIUM103
T1/2 (days) 59.4 16.97
Energy(keV) 27.4 21
Form Seeds Seeds
Implant type Permanent Permanent
Dose rate 7 19
Mean 0.42 1.3
activity/seed
Monotherapy 145Gy mPD 125Gy mPD
dose
+EBRT dose 110Gy mPD 100Gy mPD
TVL(mm) Pb 0.01 0.03
• A randomized trial
shows no different
between two arms
using two different
isotopes.
• Pd induced radiation
prostatitis is higher
than I 125 but it also
recover sooner than
that.

98. Advantages of EBRT + Brachy
• Better BED than IMRT
• Less dose to nearby critical structures
• Overall treatment time is less than 8 weeks,
hence patient is more compliant
• No issue of prostate motion

100. • Pre Planning and Ultrasound:
• Obtaining images of the entire prostate,
with 5mm spacing between slices;
• Transfer these images via cable or VCR to
the planning system
• Determination of the volume (in cubic
centimeters) of the prostate, using the
HWL (Height x Width x Length) x
Factor(0.523) for the prostate;
• Identifying in advance the technical
feasibility of the implant (anterior
urethral defects,pubic arch
interference or micro macro
calcifications).
• Drawing the boundary of the prostate:
A new file is created, corresponding to the patient inquestion;
-A coordinate system is created from the information of the "template"
images superimposed on the TRUS (transrectal ultrasound);
-Radiotherapist draws the boundaries of the prostate, seminal vesicles,
rectumand ureter in each section of the TRUS;
- Prostate volume is determined by the volumetric reconstruction of the
U.S. Distribution and quantity of seeds mCi.

101. • Preparation of material for the implant:
The charge physicist needs to control and verify the seeds that reach for
each patient. It is recommended that the physicist verify at least 10% of the
batch using a well chamber and the measure has a limit of 5% difference
between the measured activity and the certificate.
• Standards for sterilization of seeds:
The seeds are sterilized in an autoclave system the temperature of 121
centigrade and a pressure of 15 psi for 15 to 30 minutes, or the
temperature of 133 Centigrade and pressure of 30 psi for about 3 minutes
(“flash”).
- After sterilization, using Geiger monitor to check radioactivity inside of the
autoclave.
• Positioning the patient on the table:
supine and lithotomy position with legs flexed according to the
survey pre-planning.
• Anesthesia, monitoring and premedication

102. Images of the prostate via ultrasound
-Choose the largest cross section of the prostate, by transrectal
ultrasound,
as the target volume.
-Transrectal ultrasound images has a 5 mm separation of each other,
and each image is overlap with the image developed by the planning
system. It is used to call this planing image as a TEMPLATE IMAGE.
- Transfer images to the planning system identifying the prostate, urethra
and
rectum.
-Revaluate of prostate volume and calculating the number of seeds
and needles.
Insertion of needles and seeds
-Insertion of the needles is by the urologist, according to the shape
and size of the prostate and activity of the seeds under the guidance
of radiotherapist.
- Identify of each needle in the template and each length to be loaded;
-Insert of two needles, via trans perineum, approximately 1 to 1.2 cm in
the direction of the urethra after 4 and 8 hours as stabilizers.

103. Put the needle on the edge first and place them top to bottom.
- Check the positioning of each needle with sagittal images of the ultrasound.
-The needles placed in the periphery are spaced between 0.5 to 1.0 cm and 0.5
cm inside the periphery of the prostate. The typical number of needles in the
periphery is 9 to12 needles.
-The needles placed in the "Line 1" (the lowest) are separated by 1.0 cm and
about 0.5 cm from the anterior rectal wall mucosa.
-The needles in the central region of the prostate are placed at least 1.0 cm
apart from the urethra. The typical number of needles in the central region is 3
to 5.
-The standard distribution of the loads is 75% -80% of the total activity inthe
periphery and 20% -25% in the center.

104. Placement of seeds
-Guided by fluoroscopy and ultrasound at the time the surgery;
-Using the Mick applicator for the loading of individual seeds in each
needle according to the pre-planning and the eventual corrections in the time
of implantation.
-Check the seed deposition with the help of sagittal ultrasound image to the
last needle;
-The physicist and radiotherapist individually confer the number, distribution
and spacing of each seed needle immediately prior to their placement, as well
as checking the needle by fluoroscopy.
-At the end of seed deposition, potentially cold
areas identified by fluoroscopy and ultrasound
should be filled with seeds individually

105. • Cystoscopy is performed by an urologist at the end of
the introduction of seeds into the prostate.
• Radiometric survey of the room and the
patient
- Counting the number of remaining seeds and
deployed to confirm the number of seeds initially
loaded in magazines.
- Monitor the environment, professionals and the
patient with the monitor Geiger Muller,

106. Dose analysis
A quantitative dose analysis must be carried out for each patientpost
implantation.

107. Prescribed dose
1.The recommended prescription doses for Iodine-125 are 145 Gy and 110 Gy for
monotherapy and boost implants, respectively.
2.The prescription of minimum peripheral dose (mPD) is intended to cover the CTV,
and is the reference dose for the treatment.
3.X-ray CT examination is performed immediately after implant and 3 to 5 weeks
after.
4.The patient is scanned in a supine position usually with bladder contrasting. Slices with
thickness of 3 mm or less are acquired from 2 cm cephalad to the base of the gland to
2 cm caudad to the apex.
5.All of the seeds used in the implant should be encompassed in the scan.
6.ETVs (-Evaluation Treatment Volume) are determined from this scan, as the location of
the urethra and the rectum.
7.Due to the difficulty in CT visualization of the urethra, use of Foley catheterization is
strongly recommended.
8. The urethra and the rectum contours are drawn as the outer surface of the Foley
catheter and the rectal wall, respectively.
9.The CT images are used to create a post-implant treatment plan (post plan). An AP
or anterior oblique pelvic radiograph is used to verify the number of sources and this will
be recorded.
10. A surview chest CT image is obtained to check any pulmonary migration of the
source.

108. Post-Treatment Evaluation
•Biochemical assessment:
Serial PSA determinations – baseline at 3-6 months and then every6
months and/or as per institutional protocol
• Physical examination: Role of routine DRE is controversial
•Quality of Life: Urinary, bowel, and sexual function should be
prospectively assessed
•Post-Treatment Biopsy: Should be reserved for protocol settings or in
clinical situations where salvage local therapy is being considered

109. Painful bony mets:
1.External-beam radiation therapy:
20Gy/5# or 30Gy/10# & 8Gy in single fraction
↓ pain/ stabilizes bone/ ↓ chances of pathological #
2. bisphosphonates:
3. RANKL inhibitors: denosumab

110. CHEMOTHERAPY

111. 1.Docetaxel
2.Mitoxantrone.
TAX 327
1006 patients in 24 countries with HRPC
were randomized to one of three
chemotherapy regimens:
Docetaxel every 3 weeks (with
prednisone10 mg) for 10 cycles
Docetaxel every week (with prednisone
10 mg) for 5 cycles
Mitoxantrone every 3 weeks (with
prednisone 10mg) for 10 cycles
Patients who received Docetaxel every 3 weeks (with prednisone)
experienced:
• Improvement in median survival of 2 months (18.9m vs. 16.5 months)
• Greater PSA decline (45% vs. 32%)
• Improvement in Pain (35% vs. 22%)
• S/E were manageable

112. SWOG 9916
N=770 men
Dose used: Docetaxel (60mg/m2) & estramustine(280 mg orally 3
times daily from days 1 through 5) vs. mitoxantrone(12mg/m2) and
95 mg twice daily)
overall survival favored docetaxel (18.9 months compared with 16
months for mitoxantrone).
20% reduction in mortality in docetaxel &estramustine arm
Median time to progression significantly superior in the same
arm(6.3 vs.3.2 months)
Results Of SWOG & TAX 327 Confirms The Efficacy Of Docetaxel.
But Only Question Is That Only 2 Months Survival Increment IsBy
Use Of Docetaxel.

113. Salvage treatment after first-line docetaxel
All patients who receive docetaxel-based chemotherapy for CRPC will progress, thus,
there
have been many clinical trials investigating the role of salvage chemotherapy.
Several groups have used second-line intermittent docetaxel re-treatment in patients
who had clearly responded to first-line docetaxel.
Newer drugs:
• Cabazitaxel
1. a taxane derivative
2. Positive results have been published from, phase III trial (TROPIC
trial) comparing cabazitaxel + prednisone vs. mitoxantrone +
prednisone in 755 patients with CRPC, who had progressed after or
during docetaxel-based chemotherapy .
3.An OS benefit (15.1 vs. 12.7 months, p < 0.0001) was observed in
the cabazitaxel arm. As well as PFS (2.8 vs. 1.4 months, p < 0.000).
4.Treatment-associated WHO grade 3/4 side effects developed
significantly more often in the cabazitaxel arm, particularly neutropenia
and sepsis.

114. Phase 2 trials of docetaxel + atrasentan/
bevacizumab/bortezomid/capecitabine/calcitriol/thalidomide
have been completed.
 Randomized phase 2 trial of thalidomide/docetaxel
Phase 2 trial of docetaxel/calcitriol (ASCENT) strongly favoring survivalbenefit.
Mature results are anticipated within the next 3 to 5 years.
SPARC: phase III, randomized, placebo-controlled trial uses Satraplatin: novel
oral platinum compound Associated with significant PFS improvements in
chemotherapy-naive patients with hormone-refractory prostate cancer.
Immunologic Therapies
Sipuleucel-T is a product freshly prepared for each treatment course consisting of
leukapheresed mononuclear cells pulsed ex vivo with a GM-CSF/prostatic acid
phosphatase fusion protein. Patients are cytopheresed and dendritic cell precursors
isolated prior to fusion protein exposure. Two small randomized phase 3 trials have
been conducted with Sipuleucel-T, 9901 and 9902A.
Anti CTLA-4 antibody is in clinical trial
PROSTVAC-VF TRICOM VACCINE has reported phase 2 data & further studies will ensue.

115. HORMONAL THERAPY
MECHANISMS OF ANDROGEN AXIS BLOCKADE

116. The androgen-signaling axis and
its inhibitors. Testicular androgen
synthesis is regulated by the
gonadotropin-releasing
hormone (GnRH)–LH axis,
whereas adrenal androgen
synthesis is regulated by the
corticotrophin-releasing
hormone (CRH)-ACTH axis. GnRH
agonists and corticosteroids
inhibit stimulation of the testes
and adrenals, respectively.
Abiraterone inhibits CYP17, a
critical enzyme in androgen
synthesis. Bicalutamide,
flutamide, and nilutamide
competitively inhibit the binding
of androgens to androgen
receptors; enzalutamide also
blocks the translocation
of the ligand bound AR complex to the nucleus and from binding to DNA. DHEA,
dehydroepiandrosterone; DHEA-S, dehydroepiandrosterone sulphate; DHT,
dihydrotestosterone; AR, androgen receptor; ARE, androgen-response element.

118. • Male sex hormones (testosterone, androgens) are critical to growth of prostate cancer
• Normalization of PSA < 4ng/ml - 60-70%
• Tumor masses will decrease by half or more in 30-50%
• Improvement in symptoms (bone pain, urinary obstruction)- 60%
• There are four general forms of ADT:
Ablation of
androgen source
Inhibition of
LHRH or LH
Inhibition of androgen
synthesis
Antiandrogens
Orchiectomy DES
Leuprolide
Aminogluthemide Cyprotene acetate
Goserelin Ketoconazole Flutamide
Triptorelin Biclutamide
Histrelin Nilutamide
Cetrorelix
Abarelix

119. Side-effects of hormonal therapy
• Castration
• Loss of libido
• Erectile dysfunction
• Hot flashes (55–80% duringADT)
• Gynaecomastia and breast pain Increase in body fat
• Decrease in bone mineral density
• Osteoporosis
• Muscle wasting
• Anaemia (severe in 13% CAB)
• Cognitive decline
• Oestrogens
• Cardiovascular toxic effects (AMI, CHF, CVA, DVT, pulmonary embolism)
• LHRH agonists
• Flare phenomenon due to initial rise of testosterone
• Might worsen symptoms
• Costly

120. Enzalutamide :
• A novel anti-androgen that blocks AR binding, nuclear
translocation and transcription.
• Enzalutamide is used as a once-daily oral treatment.
• AFFIRM study in 2012 randomized 1,199 patients with metastatic
CRPC in a 2/1 fashion between enzalutamide or placebo. (The
patients had progressed after docetaxel treatment).
• After a median follow-up of 14.4 months, the median survival in
the enzalutamide group was 18.4 months compared to 13.6 months
in the placebo arm (HR: 0.63, p < 0.001). This led to the
recommendation that the study be halted and unblinded.
• The benefit was observed irrespective of age, baseline pain
intensity, and type of progression.

121. • CYP17 inhibitor.
• It is used once daily combined with prednisone twice daily (10 mg/ day).
• large phase III COU-AA-301 trial used a total of 1,195 patients with metastatic
CRPC were randomised in a 1/1 fashion between abiraterone acetate or placebo,
In patients with progressive disease after docetaxel therapy the median survival
in the abiraterone group was 15.8 months compared to 11.2 months in the placebo
arm (HR: 0.74, p < 0.001).
• The benefit was observed irrespective of age, baseline pain intensity, and type of
progression.
• most common grade 3/4 side effects did not differ significantly but
mineralocorticoid-related side effects were more frequent in the abiraterone
group, mainly grade 1/2 (fluid retention, oedema or hypokalaemia).
• As of today, the choice between third-line hormonal treatment
(using enzalutamide or abiraterone) or second line
chemotherapy (cabazitaxel) remains unclear with no clear
decision-making findings published.
Abiraterone Acetate

122. • Bone-seeking radiopharmaceuticals (samarium-153-
EDTMP, strontium-89):
Three radiopharmaceuticals are currently FDA-approved for the
palliative treatment of painful bone metastases
1. phosphorus-32 2.strontium-89 3.samarium-153-EDTMP.
Myelosuppression is the predominate toxicity associated with all of the bone
seeking radioisotopes.

123. Schedule Frequency
First follow up 4-6 weeks after RT
0-1 years Every 3-4 months
2-5 years Every 6 months
5+ years Annually
Examination
History & Physical
Examination
Complete History & Physical
Examination
Annual DRE
Laboratory Tests PSA every 6-12 months for 5
years and then annually
Imaging Studies Based on clinical indication
only
Follow Up

124. THANK YOU!