2. INCIDENCE
• Common in western world
• One in six American men will be diagnosed
with prostate cancer during his lifetime
• Europe, the annual incidence rates were 214
per 1000 men
3.
4. DIAGNOSIS STAGING WORK UP
• DRE
• PSA
• TRUS
• getting a histological confirmation of prostate
cancer
5. DIGITAL RECTAL EXAMINATION
• simple, cost effective method
• Positive predictive value from 21% to 53%
• Good staging method
• sensitivity of 52% and specificity of 80%
• MAY UNDER/OVER ESTIMATE
J URO 1999;161:835-9
6. PROSTATE SPECIFIC ANTIGEN
• The normal PSA are <4 ng/ml
• threshold PSA level for detection of cancer is
4.0 ng/ml
• BUT 25% will have a normal or low PSA
• PSA <10 ng/ml - low risk of peri-prostatic
spread and metastases
7. PSA
• PSA >20 ng/ml-An increased risk of peri-
prostatic spread, seminal vesicle involvement
and distant metastases
• GENERAL RULES
• PSA >10 ng/ml indicates capsularpenetration
in more than 50% patients
• PSA >50 ng/ml – metastatic disease.
8. PSA
• prostate specific
• Not cancer specific
• BPH, prostatitis, tuberculosis etc
• borderline zone of 4-10ng/ml
9. FREE TO TOTAL
• < 0.15 -a higher Gleason score ,poorer
prognosis
• free to total PSA of <0.1 is most likely
• higher percentages with BPH
JAMA 1998;279(19);1542-7
10. Prostate biopsy
• Extended biopsy is more preferable
• cancer detection rate- 40%,
• sextant biopsy -20% to 25%
REV UROLOGY 2007 SUMMER,9(3):93-98
12. • Sextant biopsies -undersample most and miss
many
• Extended biopsies increase detection rates
decrease sampling error.
• Initial biopsies should include at least 12 cores
from the peripheral zone.
• repeat biopsies - anterior apical biopsies or
saturation approaches is recommended.
.
REV URO 2007 SUMMER;9(3)::93 98
17. TREATMENT
• NATURAL HISTORY OF PROSTATE CANCER IS
DIFFICULT TO PREDICT
• Men with similar stage ,glisson score,psa can
have markedly different outcome
19. high grade prostatic intraepithelial
neoplasia (PIN)
• Not an indication for treatment
• careful follow-up, early re-biopsy to rule out
invasive cancer
• No evidence at the present for early
treatment
20. Invasive prostatic adenocarcinoma
• Localized prostate cancer (T1 – T3a N0)
• Locally advanced disease (T3b-T4 N0)
• Metastatic disease: Any T, N+ or Any T, Any N
&distant metastasis (M+)
21. Localized prostate cancer (T1 – T3a N0)
• Low risk (cT1-T2a and Gleason score 2-6 and
PSA< 10)
• Intermediate risk (cT2b-T2c or Gleason score
= 7or PSA 10-20)
•
• High Risk (cT3a or Gleason score 8-10 or PSA >
20)
22. LOW RISK
• Very low risk
gleason score-2-6
T1c
psa<10ng/ml
fewer than 3prostate core biopsies positive
<=50% cancer in each core
psa density-<0.15ng/ml/gm
• Low risk
27. ACTIVE SURVEILLANCE(AS)
• Most men with good risk prostate cancer have
indolent and slow growing disease
• risk posed by cancer can be assessed with some
degree of certainty that delayed treatment will
be as curative as immediate treatment.
• attempt to avoid over-treatment in the majority
of patients
28. AS
• low-volume, low-grade carcinoma
• elderly patients or medical comorbidities with
limited life expectancy comply for
• regular follow up
29. AS
• PSA tests and a digital rectal examination
every 3 months for 2 years
• repeat biopsy 6-12 months after the initial
diagnosis and yearly when indicated
30. ASRADICAL RX
• PSA DT of < or = 3 years (based on a minimum
of 3 determinations over 6 months) are
offered radical intervention.
• re-biopsy score
• tumor volume
• stage progression
• patient preference
urol oncol 2006 jan -feb 24(1) 46-50
31. AS
• PSA doubling time
• re-biopsy score
• , tumor volume
• stage progression
• patient preference.
32. Outcome
• AS- 85% would remain treatment-free at 5
years
• no patient died from prostate cancer.
solowey etal ..BJU INTRN 2008 JAN;101(2) 165-9
33. • 65% remained free of treatment at 8 years.
• The prostate cancer specific survival using this
approach was 99.3% at 8 years
urol oncol 2006 jan -feb 24(1) 46-50
34. Radical prostatectomy
• RP -removal of the entire prostate gland
between the urethra and the bladder, with
resection of both seminal vesicles
• is recommended for the organ confined
prostate cancer with life expectancy of >10
years
35. RP
• complete removal of cancer
• accurate pathological staging and allows
better planning for adjuvant therapy.
36. RP VS AS
j natl cancer inst 2008 aug 20;100(16) 1144-1154
37. RP VS AS
j natl cancer inst 2008 aug 20;100(16) 1144-1154
38. RP VS AS
j natl cancer inst 2008 aug 20;100(16) 1144-1154
40. RP
• Low risk
• Intermediate-risk Prostate Cancer and a life
expectancy of more than 10 years.
• prognosis -excellent when the tmr is confined
to the prostate based on pathological
examination
41. Pelvic node dissection
• Cut of-6%
• The sensitivity- 87.9%
• specificity- 54%
• negative predictive values-97.3%
• associated with the 6% cut off
int j radtn oncol biol phys 2012 jun;83(2) 624-9
42. Pelvic node dissection
• Importance-to determine adjuvant therapy
• Only ePLND
• removal of obturator, external iliac, and
hypogastric lymph nodes
int j radtn oncol biol phys 2012 jun;83(2) 624-9
44. RP in high risk prostate
• no consensus regarding the optimal treatment
of men with high-risk localized disease
• discouraged,because of increased risk of
positive surgical margins and lymph node
metastases and/or distant relapse
45. NAHT followed by RP
• THEOROTICAL ADVANTAGE
• potentially downstage locally advanced
tumors,
• thus making them more amenable achieving
negative margins at the time of surgical
resection
cochrane database syst rev.2006 octo18;(4):CD006019
46. • NHT have shown a significant decrease
• in positive surgical margins
• and lymph node metastasis,
• reductions in tumor size
• PSA levels
BUT
48. NAHT followed by RP
• Cochrane review(level of evidence: 1a)
• NAHT before RP does not provide a significant
OS advantage over prostatectomy alone
• NAHT before RP does not provide a significant
advantage in disease-free survival over
prostatectomy alone
cochrane database syst rev.2006 octo18;(4):CD006019
49. NAHT before RP does substantially
improve
• local pathological variables such as organ-
confined rates, pathological down staging,
positive surgical margins and rate of lymph
node involvement.
• NHT prior to prostatectomy is not
recommended
50. COMPLICATIONS OF RP
• mortality rate is 0-1.5%
• urinary fistulas are seen in 1.2-4% of patients
• urinary incontinence persists after one year in
7.7%
• Less complications procedure is performed in a
high-volume hospital and by a surgeon
51. • Erectile dysfunction used to occur in nearly all
patients
• nerve-sparing techniques can be applied in
early-stage disease
• nerve-sparing RP may have a higher chance of
local disease recurrence
52. RDIOTHERAPY
• No direct RCT between surgery vs RT
• Retrospective analysis not much of difference
between both modalities
• radical&palliative
• EBRT
• EBRT+BT
• BT
53. CONVENTIONAL EBRT
• Patient supine
• Hands over chest
• Immobilization –
• Four field BOX
• Shrinking field technique
54. • Superior border-L4-L5-to include the common
iliac nodes
• Inferior border-1.5 -2cm below the junction of
prostatic and membranous urethra –just
below the ischial tuberosities
• Lateral margin-1-2 c from the lateral boney
pelvis
55. • Anterior -pubic symphysis
• Posterior margin-S2-S3 junction to include the
pelvic and presacral nodes+sparing posterior
rectal wall
56.
57.
58. • Anterior -pubic symphysis
• Posterior margin-S2-S3 junction to include the
pelvic and presacral nodes+sparing posterior
rectal wall
59. Boost field
• Cystogram –
• supine ,catheter insitu-20 ml of contrast+10ml
of air introduced into bladder
• 20 ml of contrast into catheter balloon which
is pulled down to bladder base
• AP film in simulator-2cm margin is given with
bladder base as center
63. High risk
• minimum dose of 74 - 80 Gy is recommended
for high risk group(level of evidence : 1a)
64. • meta-analysis of data obtained exclusively
fromRCT’s provides evidence that high dose
RT is superior to conventional dose RT in
terms of preventing biochemical failure in low-
, intermediate-, and high-risk
• high dose RT should be offered to all patients
regardless of their risk status
int j Radiat Oncol Biol phys.2009 aug1;74(5):1405-18.
65. DOSE
• 70 and 80 Gy
• Significant increase in the 5-year Biochemical
control rate
• low-14%
• Intermediate- 17.8%
• high-risk-19.2%
(Level of evidence :1a)
66. Prophylactic WPRT
• RCT -NO benefit from prophylactic irradiation of the pelvic
lymph nodes in high-risk cases (46-50 Gy).
• risk of LN involvement of 15% to 35% -benefited the most
from pelvic nodal RT
• less than 15% or
• more than 35%(higher distant metastasis) did not benefit
from pelvicnodal RT
• (level of evidence 2b )
67. WPRT VS PORT
int j Radiat Oncol Biol Phys.2007.NOVEMBER 1;69(3)646-655
68. INTERSTETIAL BRACHYTHERAPY
• Permanent
• Temporary
• Permanent-Ideal-are those with favorable risk
prognostic features who have a high likelihood
of organ-confined disease
69. • PSA levels 10ng/mL or less,
• Gleason scores less than 6-7,
• Clinical stages T1b- T2a
• prostate volume of < 50 cm3 and
• good International Prostatic Symptom Score
(IPSS)
70. International Prostate Symptom Score
• International Prostate Symptom Score
(IPSS) is an 8 question (7 symptom questions +
1 quality of life question)
71. IPSS result of 7 symptoms questions
Score Correlation[1]
0-7 Mildly symptomatic
8-19 Moderately symptomatic
20-35 Severely symptomatic
73. EBRT+BRACHY
• intermediate and highrisk patients with
localized prostate cancer
• I 125 seeds or Pd 103
• EBRT-45 to 50 Gy - conventional / conformal
75. • HDR brachytherapy-trans-perineal placement of
after-loading catheters in the prostate under
ultrasound guidance.
• CT-based treatment planning
• DOSE-4 to 6 Gy –each 24 to 36 hours using
192Ir.
Followed by EBRT
dose of 45 to 50.4 Gy using conventional
fractionation
76. HDR-advantage
• more easily optimize the delivery of RT to the
prostate
• reducing the potential for under-dosage ,
• reduces radiation exposure
• radiobiologically more efficacious in terms of
tumor cell kill for patients with increased
tumor bulk or adverse prognostic features.
.
77. EBRT vs EBRT+LDR vs EBRT+HDR
• EBRT+HDR - give better biochemical control&
better overall survival as compared to external
beam radiotherapy alone.
• biochemical control rates with LDR was
comparable to that of HDR
• overall survival was better with HDR
brachytherapy.
• (Level of evidence: 1a)
RADIOTHERAPY&ONCOLOGY(2009);VOLUME:93,ISSUE 2
78. POST OP RT
• Indication-positive surgical margins, seminal
vesicle invasion and/or extracapsular
extension
• recommended doses are 60-64Gy
• (level of evidence:1)
radiother oncol.2008 jul88(1)
80. POST OP RT
• Immediate vs late
• Immediate postoperative radiotherapy -well
tolerated, with
• grade 3-4 urinary toxicity of less than 3.5%
without significant differences regarding the
rate of incontinence and/or stricture of
anastomosis.
82. Androgen deprivation therapy
• Clinically localized disease
• Neo adjuvant/concomitant/adjuvant-prolongs
survival in radiation managed patients
• When ever used cab should use
• Indicated in all high risk + locally advanced +
metastatic disease(2-3 yrs)
• Short term androgen deprivation in
intermediate risk (4-6 months)
89. Surgery
• Lymph node-positive (N+) disease will mostly
be followed by systemic disease
progression, and all patients with significant
N+ disease will ultimately fail treatment.
90. RADIATION THERAPY
• INDICATION
• pelvic lymph node involvement lower than the
iliac regional nodes,
• younger than 80 years old
• WHO performance status 0-1 and
• no severe co-morbidity
91. • External beam irradiation plus immediate
long-term hormonal manipulation-
• (level of evidence : 1b)
92. DISTANT METASTATIC DISEASE
• Immediate hormone therapy is indicated
• should be offered early to all patients
• BOTH symptomatic and asymptomatic
• (level of evidence:1).
93. • Response rate-85%
• median duration of response of 18 months
• median survival of 36 months.
• median survival of 36 months
• ranges between 28 and 53 months
• >10 yrs-only 7%
94. osseous metastases:
• Surgical intervention-Decompressive surgery
in spinal cord compression
• Pathological fracture of weight bearing bones
in patients with reasonable life-expectancy
95. RADIATION THERAPY
• EBRT-for painful or unstable skeletal
metastases
• DOSE -800 CGY –SINGLE fraction(Level of
evidence: 1b)
• Fractionated RT for bone metastases may be
considered-spinal cord compression
96. 30/10 vs 800 single
• acute toxicity was more frequent in the 30-Gy
arm
30/10-17%
8-Gy arm 10%
Late toxicity-rare in both arms & is same
4%-in both arms
J Natl Cancer Inst.2005 jun 1;97(11)
97. • overall response
• 8-Gy
Complete -15%
partial response - 50%
• 30-Gy
Complete- 18%
Partial- 48% in the arm
100. Bisphosphanates
• reduce bone pains
• skeletal-related events including fractures
• inhibit
osteoclast-mediated bone resorption and
osteoclast precursors
effective-HRPC
response rate of 70-80%
101. • reduce pain
• provide total pain relief
• Effect more important- HRPC
• Decreases pathological fractures-10%
• skeletal related events-11%
• time to first skeletal-related event-prolonged
• Toxicity-osteo necrosis jaw necrosis,
102. HORMONAL THERAPY
• Androgen deprivation- suppressing the
secretion of testicular androgens –
surgical
medical castration
• Anti-androgens -inhibiting the action of the
circulating androgens at the level of their
receptor in prostate cells
103. • When two modalities can be combined-
complete (or maximal or total) androgen
blockade (CAB).
104. b/l orchidectomy
• Simple&quickest way to achieve a castration
level
• Usually- obtained in less than 12 hours
• main drawback- negative psychological effect
105. Long acting LHRH agonist
• Currently the predominant forms of ADT
• Synthetic analogues of LHRH
• interfere with the hypothalamic-pituitary-
gonadal axis
• initially stimulate pituitary LHRH receptors
• inducing a transient rise in LH and FSH release
106. • consequently elevate testosterone
• testosterone surge or ‘flare up’ phenomenon
• begins 2-3 days of first injection and lasts
through first week
• comparable efficacy to orchiectomy (level of
evidence: 1a)
• Currently standard of care in hormonal
therapy
107. • detrimental effects- flare phenomenon
increased bone pain, acute bladder outlet
obstruction,obstructive renal failure, spinal
cord compression
• fatal cardiovascular events due to hyper-
coagulation status
108. Anti androgens
• compete with testosterone and DHT for
binding sites on their receptors in the prostate
cell nucleus
• promoting apoptosis and inhibiting Prostate
Cancer growth
• Steroidal& non steroidal
• Both competes with androgen at receptor but
109. • steroidal anti-androgens additional
progestational properties with central
inhibition of the pituitary gland
• M1 patients, an improvement in OS with
castration
• M0 patients no significant difference in OS
110. Intermittent Vs Continuous Androgen
Deprivation
• long-term CAB- which stimulates prostate cell
apoptosis
• fails to eliminate the entire malignant cell
population
• after a variable period-tumor invariably
relapse- averaging 24 months
• Androgenindependent state of growth
111. Androgen-independent progression
• begin early after the administration of HT
• Coinciding with the cessation of androgen-
induced differentiation of stem cells
• cyclical ADT can make a clone –still
sussceptable to ADT
112. Biochemical relapse after local therapy
• RP- undetectable within 3 weeks
• Persistently elevated PSA- PSA-producing
tissue remains in the body
• rapidly increasing PSA level- distant
metastases(first 2yrs)
• slowly increasing-local reccurrence
• two consecutive values of 0.2 ng/mL or
greater
113. • RARELY-undifferentiated tumors- local
treatment failure and distant metastases-
undetectable PSA levels
• 50%-50%-local failure-distant mets
114. RADIATION THERAPY
• PSA nadir of less than 0.5 ng/mL
• Interval for nadir varying some times very
long-3yrs
• biochemical failure-Rising PSA->2ng/ml-above
nadir psa
• Three consecutive PSA rises
• late and slowly rising PSA is a sign of local
failure
115. LOCAL RECCURRENCE
• prostatic biopsy demonstrating malignant
cells18 months or longer after initial
radiotherapy
• PLUS associated psa elvation
• No mets detected-MRI,CT,BONE SCAN
116. HRPC-hormone refractory prostate
cancer
• Serum castration levels of testosterone (< 50
ng/dL, or < 1.7 nmol/L)
• 3 consecutive rises of PSA, 1 week
apart, resulting in two 50% increases over the
nadir, with a PSA > 2 ng/mL
• PSA progression, despite secondary hormonal
manipulations
118. • 1/3 will respond to anti androgen withdrawal
> 50% PSA decrease in 4 moths
• flutamide was replaced by bicalutamide and
vice versa
• Aminoglutethimide, ketoconazole and
corticosteroids-also have some role with –anti
androgen therapy
• DES-20-80% response rate but more
complication
133. RT in Combined Approach
• Surgery + Adjuvant RT (Ind: ECE ,Margin+ or SVI)
• SWOG 8794 : 431pts: Observation Vs. RT 60- 64Gy
• 15yr OS:38->46%,bF:77->55%,LF:22%->8%.
• QOL worse initially , later better.
• EORTC 22911 : 1005 pts : Obsn Vs. RT 60Gy
• 5yr OS: No diff,bPFS:5374%,LRF: 15 5%,
• No significant diff in toxicities-02
• Salvage RT after RP: beneficial if PSA-DT< 6-10month
• LN-,lower pre-RT PSA,GS<8.
• Increases Prostate cancer Specific Survival.
•
134. • RT + short term HT (STHT)
• 3-6 months of HT improves bPFS by 15-25% and CSS
by 3-8% Vs. No HT.
• TTROG(Denha et al.2005),Crook et al.( 2004),RTOG
9413, Lavadiere et al
• D’Amico et al and RTOG 8610 trials showed 10-15%
OS benefit.
• RT + long term HT
• For high risk patients, HT for >2-3 yrs improves OS
by 10-15% ,CSS by 5% and DFS by 20-30% Vs. no HT or
4-6 month HT.
• (RTOG 8531,EORTC 22863,RTOG 9202,EORTC
22961)
•
135. • PSA & DRE :every 6 months for 5yrs,then annually.
• PSA FAILURE
• Phoenix definition : current ASTRO/RTOG
• EBRT with/without short term HT
• - a rise by ≥2 ng/mL above the nadir PSA.
• PSA nadir : After RP : 3 weeks
• EBRT:2-3yrs
• Brachytherapy : 3-4 yrs
• PSA bounce : transient PSA rises(<2ng/ml)
• EBRT & Brachytherapy:20%
• (9-14mnths)
137. • Late toxicities :
• Urinary stricture : <4 %
• If prior TURP/prostatectomy
• 4-9 % stricture/stress incontinence
• Post treatment Impotence :
• Brachy (24%),EBRT + Brachy (40%),EBRT alone(45%), Nerve
Sparing RP(66%), Non Nerve sparing RP (75%).
• Robinson JW et al. Int J Radiat Oncol Biol Phys
2002;54:1063-1068.
• Perioperative complications : Obstructive symptoms (10%), Urinary
incontinence (1-3%),rectal injury (1-5%)
• Second cancers :(SEER, Tward 2008) No significant difference ,
• RP Vs. EBRT
138. Future directions
• Dose escalation
• 70.2 Gy Vs. 79.2Gy :T1b-T2b,High dose less likely to have
local failure , HR=.57, 10yr BF: 32.4% Vs. 16% in high dose.
Zietman et al JCO 2010 Mar 1;28(7):1106-11
• Proton Therapy
• Molecular agents & New chemotherapy agents
• Immunotherapy Sipuleucel-T-relative reduction of 22% in
the risk of death NEJM 2010 Jul 29;363(5):411-22
139. summery
• Role of Radiotherapy in Ca Prostate is time-
tested.
• All stages and risk groups are benefitted with
RT.
• In future , Radiobiology research , Molecular
Pathways and Technological innovations are
the keys to enhance the treatment.
