0
Carcinoma prostate
Dr kiran p
Junior resident radiotherapy
INCIDENCE
• Common in western world
• One in six American men will be diagnosed
with prostate cancer during his lifetime
•...
DIAGNOSIS STAGING WORK UP
• DRE
• PSA
• TRUS
• getting a histological confirmation of prostate
cancer
DIGITAL RECTAL EXAMINATION
• simple, cost effective method
• Positive predictive value from 21% to 53%
• Good staging meth...
PROSTATE SPECIFIC ANTIGEN
• The normal PSA are <4 ng/ml
• threshold PSA level for detection of cancer is
4.0 ng/ml
• BUT 2...
PSA
• PSA >20 ng/ml-An increased risk of peri-
prostatic spread, seminal vesicle involvement
and distant metastases
• GENE...
PSA
• prostate specific
• Not cancer specific
• BPH, prostatitis, tuberculosis etc
• borderline zone of 4-10ng/ml
FREE TO TOTAL
• < 0.15 -a higher Gleason score ,poorer
prognosis
• free to total PSA of <0.1 is most likely
• higher perce...
Prostate biopsy
• Extended biopsy is more preferable
• cancer detection rate- 40%,
• sextant biopsy -20% to 25%
REV UROLOG...
BIOPSY
• Sextant biopsies -undersample most and miss
many
• Extended biopsies increase detection rates
decrease sampling error.
•...
CT/MRI
• T1&T2-with probability of LN
involvement>10%
• T3-T4
• DREsize, location, volume, local extension
• TRUS/Endorectal coil MRIlocal extension
• CT/ProstaScint Scanpre-op pelv...
Bone scan
• MRI superior?
• Indication
T1+PSA >20
T2+PSA>10
Gleason score >=8
T3&T4
Predictive models in Ca prostate
TREATMENT
• NATURAL HISTORY OF PROSTATE CANCER IS
DIFFICULT TO PREDICT
• Men with similar stage ,glisson score,psa can
hav...
OUTCOME WITH SCREENING
J natl Cancer inst.2009 March 18;101(6)
high grade prostatic intraepithelial
neoplasia (PIN)
• Not an indication for treatment
• careful follow-up, early re-biops...
Invasive prostatic adenocarcinoma
• Localized prostate cancer (T1 – T3a N0)
• Locally advanced disease (T3b-T4 N0)
• Metas...
Localized prostate cancer (T1 – T3a N0)
• Low risk (cT1-T2a and Gleason score 2-6 and
PSA< 10)
• Intermediate risk (cT2b-T...
LOW RISK
• Very low risk
gleason score-2-6
T1c
psa<10ng/ml
fewer than 3prostate core biopsies positive
<=50% cancer in eac...
Life expectancy -<5yr-any risk
• If asymptomatic –no further work up or
treatment
Very low risk
• Life expectancy -<20yrs-AS
• PSA -3MONTHLY
• DRE-6MONTHLY
• Repeat biopsy-yrly
Low risk
• cT1-T2a and Gleason score 2-6 and PSA< 1
• Life expectancy<10yr,>10yr
Life
expectancy
<10 yrs
AS
>10 yrs
AS
RADICAL
RX
SX RT
EBRT
BRACHY
ACTIVE SURVEILLANCE(AS)
• Most men with good risk prostate cancer have
indolent and slow growing disease
• risk posed by c...
AS
• low-volume, low-grade carcinoma
• elderly patients or medical comorbidities with
limited life expectancy comply for
•...
AS
• PSA tests and a digital rectal examination
every 3 months for 2 years
• repeat biopsy 6-12 months after the initial
d...
ASRADICAL RX
• PSA DT of < or = 3 years (based on a minimum
of 3 determinations over 6 months) are
offered radical interv...
AS
• PSA doubling time
• re-biopsy score
• , tumor volume
• stage progression
• patient preference.
Outcome
• AS- 85% would remain treatment-free at 5
years
• no patient died from prostate cancer.
solowey etal ..BJU INTRN ...
• 65% remained free of treatment at 8 years.
• The prostate cancer specific survival using this
approach was 99.3% at 8 ye...
Radical prostatectomy
• RP -removal of the entire prostate gland
between the urethra and the bladder, with
resection of bo...
RP
• complete removal of cancer
• accurate pathological staging and allows
better planning for adjuvant therapy.
RP VS AS
j natl cancer inst 2008 aug 20;100(16) 1144-1154
RP VS AS
j natl cancer inst 2008 aug 20;100(16) 1144-1154
RP VS AS
j natl cancer inst 2008 aug 20;100(16) 1144-1154
RP
• Retro pubic
• Perineal
• Retro pubic-common, enables simultaneous
pelvic lymph node assessment
• Robotic assisted-mor...
RP
• Low risk
• Intermediate-risk Prostate Cancer and a life
expectancy of more than 10 years.
• prognosis -excellent when...
Pelvic node dissection
• Cut of-6%
• The sensitivity- 87.9%
• specificity- 54%
• negative predictive values-97.3%
• associ...
Pelvic node dissection
• Importance-to determine adjuvant therapy
• Only ePLND
• removal of obturator, external iliac, and...
Pelvic node dissection
• No use <10 nodes
• 28 nodesnodes
RP in high risk prostate
• no consensus regarding the optimal treatment
of men with high-risk localized disease
• discoura...
NAHT followed by RP
• THEOROTICAL ADVANTAGE
• potentially downstage locally advanced
tumors,
• thus making them more amena...
• NHT have shown a significant decrease
• in positive surgical margins
• and lymph node metastasis,
• reductions in tumor ...
• NO DIFFERENCE IN DESEASE FREE SURVIVAL
• OVERALL SURVIVAL
NAHT followed by RP
• Cochrane review(level of evidence: 1a)
• NAHT before RP does not provide a significant
OS advantage ...
NAHT before RP does substantially
improve
• local pathological variables such as organ-
confined rates, pathological down ...
COMPLICATIONS OF RP
• mortality rate is 0-1.5%
• urinary fistulas are seen in 1.2-4% of patients
• urinary incontinence pe...
• Erectile dysfunction used to occur in nearly all
patients
• nerve-sparing techniques can be applied in
early-stage disea...
RDIOTHERAPY
• No direct RCT between surgery vs RT
• Retrospective analysis not much of difference
between both modalities
...
CONVENTIONAL EBRT
• Patient supine
• Hands over chest
• Immobilization –
• Four field BOX
• Shrinking field technique
• Superior border-L4-L5-to include the common
iliac nodes
• Inferior border-1.5 -2cm below the junction of
prostatic and m...
• Anterior -pubic symphysis
• Posterior margin-S2-S3 junction to include the
pelvic and presacral nodes+sparing posterior
...
• Anterior -pubic symphysis
• Posterior margin-S2-S3 junction to include the
pelvic and presacral nodes+sparing posterior
...
Boost field
• Cystogram –
• supine ,catheter insitu-20 ml of contrast+10ml
of air introduced into bladder
• 20 ml of contr...
DOSE
• Conventional-60 to 70gy/1.8-2gy per fraction
DOSE escalation
• Depends on risk
• Low risk-a minimum dose of 70 - 74 Gy is
(external with / without brachytherapy)
• Ide...
Intermediate risk
• minimum dose of 74 - 76 Gy is recommended
for Int risk group(level of evidence : 2)
High risk
• minimum dose of 74 - 80 Gy is recommended
for high risk group(level of evidence : 1a)
• meta-analysis of data obtained exclusively
fromRCT’s provides evidence that high dose
RT is superior to conventional dos...
DOSE
• 70 and 80 Gy
• Significant increase in the 5-year Biochemical
control rate
• low-14%
• Intermediate- 17.8%
• high-r...
Prophylactic WPRT
• RCT -NO benefit from prophylactic irradiation of the pelvic
lymph nodes in high-risk cases (46-50 Gy)....
WPRT VS PORT
int j Radiat Oncol Biol Phys.2007.NOVEMBER 1;69(3)646-655
INTERSTETIAL BRACHYTHERAPY
• Permanent
• Temporary
• Permanent-Ideal-are those with favorable risk
prognostic features who...
• PSA levels 10ng/mL or less,
• Gleason scores less than 6-7,
• Clinical stages T1b- T2a
• prostate volume of < 50 cm3 and...
International Prostate Symptom Score
• International Prostate Symptom Score
(IPSS) is an 8 question (7 symptom questions +...
IPSS result of 7 symptoms questions
Score Correlation[1]
0-7 Mildly symptomatic
8-19 Moderately symptomatic
20-35 Severely...
• not recommended for patients with locally
advanced disease
EBRT+BRACHY
• intermediate and highrisk patients with
localized prostate cancer
• I 125 seeds or Pd 103
• EBRT-45 to 50 Gy...
• low-dose-rate boost -dose 90-100 Gy for
103Pd implants
• 110 Gy for 125I implants
• HDR brachytherapy-trans-perineal placement of
after-loading catheters in the prostate under
ultrasound guidance.
• CT-ba...
HDR-advantage
• more easily optimize the delivery of RT to the
prostate
• reducing the potential for under-dosage ,
• redu...
EBRT vs EBRT+LDR vs EBRT+HDR
• EBRT+HDR - give better biochemical control&
better overall survival as compared to external...
POST OP RT
• Indication-positive surgical margins, seminal
vesicle invasion and/or extracapsular
extension
• recommended d...
evidence
POST OP RT
• Immediate vs late
• Immediate postoperative radiotherapy -well
tolerated, with
• grade 3-4 urinary toxicity o...
• immediate post-operative radiotherapy -
better
• five-year clinical or biological survival:
• Immediate- 72.2% vs 51.8% ...
Androgen deprivation therapy
• Clinically localized disease
• Neo adjuvant/concomitant/adjuvant-prolongs
survival in radia...
Adverse effect
• Hot flushes
• vasomotor instability
• Osteoporosis
• Obesity insulin resistance
• Greater risk of DM, car...
locally advance Prostate Cancer
(T3b-T4)
• Neo-adjuvant hormone therapy followed by
Radical radiation therapy
• Neo-adjuva...
Treatment of Metastatic Disease
• a) Metastatic nodal (N+) disease
• b) Distant Metastatic (M+) disease
Metastatic nodal (N+) disease
Treatment Options include:
Hormanet therapy
Watchful waiting (WW)
Surgery
Radiation therapy
HORMONE THERAPY
• mainstay of treatment -of long term hormonal
therapy
• local therapy- with radiation therapy
preferred
Watchful waiting (WW)
• Elderly patients
Surgery
• Lymph node-positive (N+) disease will mostly
be followed by systemic disease
progression, and all patients with ...
RADIATION THERAPY
• INDICATION
• pelvic lymph node involvement lower than the
iliac regional nodes,
• younger than 80 year...
• External beam irradiation plus immediate
long-term hormonal manipulation-
• (level of evidence : 1b)
DISTANT METASTATIC DISEASE
• Immediate hormone therapy is indicated
• should be offered early to all patients
• BOTH sympt...
• Response rate-85%
• median duration of response of 18 months
• median survival of 36 months.
• median survival of 36 mon...
osseous metastases:
• Surgical intervention-Decompressive surgery
in spinal cord compression
• Pathological fracture of we...
RADIATION THERAPY
• EBRT-for painful or unstable skeletal
metastases
• DOSE -800 CGY –SINGLE fraction(Level of
evidence: 1...
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 ...
• overall response
• 8-Gy
Complete -15%
partial response - 50%
• 30-Gy
Complete- 18%
Partial- 48% in the arm
Hemibody radiation
• Multiple symptomatic skeletal metastases
• 8 Gy for UHBI& 6 Gy for LHBI
Systemic radionuclide therapy
• Strontium89
• Samarium153
• improve bone pains in upto 70% patients
Bisphosphanates
• reduce bone pains
• skeletal-related events including fractures
• inhibit
osteoclast-mediated bone resor...
• reduce pain
• provide total pain relief
• Effect more important- HRPC
• Decreases pathological fractures-10%
• skeletal ...
HORMONAL THERAPY
• Androgen deprivation- suppressing the
secretion of testicular androgens –
surgical
medical castration
•...
• When two modalities can be combined-
complete (or maximal or total) androgen
blockade (CAB).
b/l orchidectomy
• Simple&quickest way to achieve a castration
level
• Usually- obtained in less than 12 hours
• main draw...
Long acting LHRH agonist
• Currently the predominant forms of ADT
• Synthetic analogues of LHRH
• interfere with the hypot...
• consequently elevate testosterone
• testosterone surge or ‘flare up’ phenomenon
• begins 2-3 days of first injection and...
• detrimental effects- flare phenomenon
increased bone pain, acute bladder outlet
obstruction,obstructive renal failure, s...
Anti androgens
• compete with testosterone and DHT for
binding sites on their receptors in the prostate
cell nucleus
• pro...
• steroidal anti-androgens additional
progestational properties with central
inhibition of the pituitary gland
• M1 patien...
Intermittent Vs Continuous Androgen
Deprivation
• long-term CAB- which stimulates prostate cell
apoptosis
• fails to elimi...
Androgen-independent progression
• begin early after the administration of HT
• Coinciding with the cessation of androgen-...
Biochemical relapse after local therapy
• RP- undetectable within 3 weeks
• Persistently elevated PSA- PSA-producing
tissu...
• RARELY-undifferentiated tumors- local
treatment failure and distant metastases-
undetectable PSA levels
• 50%-50%-local ...
RADIATION THERAPY
• PSA nadir of less than 0.5 ng/mL
• Interval for nadir varying some times very
long-3yrs
• biochemical ...
LOCAL RECCURRENCE
• prostatic biopsy demonstrating malignant
cells18 months or longer after initial
radiotherapy
• PLUS as...
HRPC-hormone refractory prostate
cancer
• Serum castration levels of testosterone (< 50
ng/dL, or < 1.7 nmol/L)
• 3 consec...
management
• anti-androgen withdrawal
• addition of ant androgens
• anti-androgen replacement
• estrogenic compounds,
• ad...
• 1/3 will respond to anti androgen withdrawal
> 50% PSA decrease in 4 moths
• flutamide was replaced by bicalutamide and
...
Cytotoxic chemotherapy
• Docetaxel containing CT-progress within 6 to8
months
• So toxicity should balanced with benefit
ROLE OF RT
• Conventional-four field box f/b boost to
prostate and seminal vessicle-but rectal and
bladder toxicities more
• 3 Dimensional Conformal techniques.
• Multi-leaf collimators to “shape” fields
• Reduced toxicities but no selective “sp...
Intensity modulated Radiotherapy
• Multiple non-coplanar beams ->
• Inverse planning -> different
• intensities -> highly ...
Image Guided RT (IGRT)
• EPID, USG with Fiducial markers etc
• Recently , CBCT-kV or MV ,
• Tomotherapy ,Cyberknife etc
Conformal RT
• 3DCRTIMRT boost /IMRT alone
Respiratory motion
• Superior –inferior-2.9+/-1.7
• Anterior-posterior-1.6+/-1.1
• ABS :monotherapy :T1c-T2a, GS<7,PSA≤10
• + EBRT : T≥2c, GS ≥7, PSA >10
• C/I :metastases, gross seminal vesicle J
• invo...
Permanent seed implants
• IODINE(I 125) & PALLADIUM (Pd 103 )
• Preplanned Transperineal
• Implantation (Seattle Method)
•...
HDR-BRACHY
• After loading catheters under trus guidence
• I192
• After EBRT-9.5 GY-two fractions
• Monotherapy-9.5GY bid ...
LDR BRACHYTHERAPY
HDR BRACHYTHERAPY
RT in Combined Approach
• Surgery + Adjuvant RT (Ind: ECE ,Margin+ or SVI)
• SWOG 8794 : 431pts: Observation Vs. RT 60- 64...
• 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...
• PSA & DRE :every 6 months for 5yrs,then annually.
• PSA FAILURE
• Phoenix definition : current ASTRO/RTOG
• EBRT with/wi...
Treatment related toxicities
• Late toxicities :
• Urinary stricture : <4 %
• If prior TURP/prostatectomy
• 4-9 % stricture/stress incontinence
• Post ...
Future directions
• Dose escalation
• 70.2 Gy Vs. 79.2Gy :T1b-T2b,High dose less likely to have
local failure , HR=.57, 10...
summery
• Role of Radiotherapy in Ca Prostate is time-
tested.
• All stages and risk groups are benefitted with
RT.
• In f...
Thank you
Carcinoma prostate
Carcinoma prostate
Carcinoma prostate
Carcinoma prostate
Carcinoma prostate
Carcinoma prostate
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  1. 1. Carcinoma prostate Dr kiran p Junior resident radiotherapy
  2. 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. 3. DIAGNOSIS STAGING WORK UP • DRE • PSA • TRUS • getting a histological confirmation of prostate cancer
  4. 4. 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
  5. 5. 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
  6. 6. 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.
  7. 7. PSA • prostate specific • Not cancer specific • BPH, prostatitis, tuberculosis etc • borderline zone of 4-10ng/ml
  8. 8. 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
  9. 9. Prostate biopsy • Extended biopsy is more preferable • cancer detection rate- 40%, • sextant biopsy -20% to 25% REV UROLOGY 2007 SUMMER,9(3):93-98
  10. 10. BIOPSY
  11. 11. • 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
  12. 12. CT/MRI • T1&T2-with probability of LN involvement>10% • T3-T4
  13. 13. • DREsize, location, volume, local extension • TRUS/Endorectal coil MRIlocal extension • CT/ProstaScint Scanpre-op pelvic node assessment • Bone Scanmets
  14. 14. Bone scan • MRI superior? • Indication T1+PSA >20 T2+PSA>10 Gleason score >=8 T3&T4
  15. 15. Predictive models in Ca prostate
  16. 16. TREATMENT • NATURAL HISTORY OF PROSTATE CANCER IS DIFFICULT TO PREDICT • Men with similar stage ,glisson score,psa can have markedly different outcome
  17. 17. OUTCOME WITH SCREENING J natl Cancer inst.2009 March 18;101(6)
  18. 18. 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
  19. 19. 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+)
  20. 20. 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)
  21. 21. 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
  22. 22. Life expectancy -<5yr-any risk • If asymptomatic –no further work up or treatment
  23. 23. Very low risk • Life expectancy -<20yrs-AS • PSA -3MONTHLY • DRE-6MONTHLY • Repeat biopsy-yrly
  24. 24. Low risk • cT1-T2a and Gleason score 2-6 and PSA< 1 • Life expectancy<10yr,>10yr
  25. 25. Life expectancy <10 yrs AS >10 yrs AS RADICAL RX SX RT EBRT BRACHY
  26. 26. 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
  27. 27. AS • low-volume, low-grade carcinoma • elderly patients or medical comorbidities with limited life expectancy comply for • regular follow up
  28. 28. 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
  29. 29. ASRADICAL 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
  30. 30. AS • PSA doubling time • re-biopsy score • , tumor volume • stage progression • patient preference.
  31. 31. 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
  32. 32. • 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
  33. 33. 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
  34. 34. RP • complete removal of cancer • accurate pathological staging and allows better planning for adjuvant therapy.
  35. 35. RP VS AS j natl cancer inst 2008 aug 20;100(16) 1144-1154
  36. 36. RP VS AS j natl cancer inst 2008 aug 20;100(16) 1144-1154
  37. 37. RP VS AS j natl cancer inst 2008 aug 20;100(16) 1144-1154
  38. 38. RP • Retro pubic • Perineal • Retro pubic-common, enables simultaneous pelvic lymph node assessment • Robotic assisted-more magnification –reduce morbidity
  39. 39. 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
  40. 40. 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
  41. 41. 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
  42. 42. Pelvic node dissection • No use <10 nodes • 28 nodesnodes
  43. 43. 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
  44. 44. 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
  45. 45. • NHT have shown a significant decrease • in positive surgical margins • and lymph node metastasis, • reductions in tumor size • PSA levels BUT
  46. 46. • NO DIFFERENCE IN DESEASE FREE SURVIVAL • OVERALL SURVIVAL
  47. 47. 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
  48. 48. 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
  49. 49. 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
  50. 50. • 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
  51. 51. RDIOTHERAPY • No direct RCT between surgery vs RT • Retrospective analysis not much of difference between both modalities • radical&palliative • EBRT • EBRT+BT • BT
  52. 52. CONVENTIONAL EBRT • Patient supine • Hands over chest • Immobilization – • Four field BOX • Shrinking field technique
  53. 53. • 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
  54. 54. • Anterior -pubic symphysis • Posterior margin-S2-S3 junction to include the pelvic and presacral nodes+sparing posterior rectal wall
  55. 55. • Anterior -pubic symphysis • Posterior margin-S2-S3 junction to include the pelvic and presacral nodes+sparing posterior rectal wall
  56. 56. 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
  57. 57. DOSE • Conventional-60 to 70gy/1.8-2gy per fraction
  58. 58. DOSE escalation • Depends on risk • Low risk-a minimum dose of 70 - 74 Gy is (external with / without brachytherapy) • Ideal-75-79 GY for low risk • Intermediate &high risk-can extent to 81GY. • (level of evidence : 2)
  59. 59. Intermediate risk • minimum dose of 74 - 76 Gy is recommended for Int risk group(level of evidence : 2)
  60. 60. High risk • minimum dose of 74 - 80 Gy is recommended for high risk group(level of evidence : 1a)
  61. 61. • 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.
  62. 62. 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)
  63. 63. 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 )
  64. 64. WPRT VS PORT int j Radiat Oncol Biol Phys.2007.NOVEMBER 1;69(3)646-655
  65. 65. INTERSTETIAL BRACHYTHERAPY • Permanent • Temporary • Permanent-Ideal-are those with favorable risk prognostic features who have a high likelihood of organ-confined disease
  66. 66. • 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)
  67. 67. International Prostate Symptom Score • International Prostate Symptom Score (IPSS) is an 8 question (7 symptom questions + 1 quality of life question)
  68. 68. IPSS result of 7 symptoms questions Score Correlation[1] 0-7 Mildly symptomatic 8-19 Moderately symptomatic 20-35 Severely symptomatic
  69. 69. • not recommended for patients with locally advanced disease
  70. 70. EBRT+BRACHY • intermediate and highrisk patients with localized prostate cancer • I 125 seeds or Pd 103 • EBRT-45 to 50 Gy - conventional / conformal
  71. 71. • low-dose-rate boost -dose 90-100 Gy for 103Pd implants • 110 Gy for 125I implants
  72. 72. • 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
  73. 73. 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. .
  74. 74. 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
  75. 75. 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)
  76. 76. evidence
  77. 77. 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.
  78. 78. • immediate post-operative radiotherapy - better • five-year clinical or biological survival: • Immediate- 72.2% vs 51.8% (p < 0.0001)
  79. 79. 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)
  80. 80. Adverse effect • Hot flushes • vasomotor instability • Osteoporosis • Obesity insulin resistance • Greater risk of DM, cardiac diseses
  81. 81. locally advance Prostate Cancer (T3b-T4) • Neo-adjuvant hormone therapy followed by Radical radiation therapy • Neo-adjuvant hormone therapy followed by Radical prostatectomy • Hormonal therapy alone • Watchful waiting - Elderly patients with limited life expectancy
  82. 82. Treatment of Metastatic Disease • a) Metastatic nodal (N+) disease • b) Distant Metastatic (M+) disease
  83. 83. Metastatic nodal (N+) disease Treatment Options include: Hormanet therapy Watchful waiting (WW) Surgery Radiation therapy
  84. 84. HORMONE THERAPY • mainstay of treatment -of long term hormonal therapy • local therapy- with radiation therapy preferred
  85. 85. Watchful waiting (WW) • Elderly patients
  86. 86. 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.
  87. 87. 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
  88. 88. • External beam irradiation plus immediate long-term hormonal manipulation- • (level of evidence : 1b)
  89. 89. DISTANT METASTATIC DISEASE • Immediate hormone therapy is indicated • should be offered early to all patients • BOTH symptomatic and asymptomatic • (level of evidence:1).
  90. 90. • 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%
  91. 91. osseous metastases: • Surgical intervention-Decompressive surgery in spinal cord compression • Pathological fracture of weight bearing bones in patients with reasonable life-expectancy
  92. 92. 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
  93. 93. 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)
  94. 94. • overall response • 8-Gy Complete -15% partial response - 50% • 30-Gy Complete- 18% Partial- 48% in the arm
  95. 95. Hemibody radiation • Multiple symptomatic skeletal metastases • 8 Gy for UHBI& 6 Gy for LHBI
  96. 96. Systemic radionuclide therapy • Strontium89 • Samarium153 • improve bone pains in upto 70% patients
  97. 97. Bisphosphanates • reduce bone pains • skeletal-related events including fractures • inhibit osteoclast-mediated bone resorption and osteoclast precursors effective-HRPC response rate of 70-80%
  98. 98. • 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,
  99. 99. 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
  100. 100. • When two modalities can be combined- complete (or maximal or total) androgen blockade (CAB).
  101. 101. b/l orchidectomy • Simple&quickest way to achieve a castration level • Usually- obtained in less than 12 hours • main drawback- negative psychological effect
  102. 102. 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
  103. 103. • 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
  104. 104. • 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
  105. 105. 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
  106. 106. • 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
  107. 107. 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
  108. 108. 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
  109. 109. 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
  110. 110. • RARELY-undifferentiated tumors- local treatment failure and distant metastases- undetectable PSA levels • 50%-50%-local failure-distant mets
  111. 111. 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
  112. 112. LOCAL RECCURRENCE • prostatic biopsy demonstrating malignant cells18 months or longer after initial radiotherapy • PLUS associated psa elvation • No mets detected-MRI,CT,BONE SCAN
  113. 113. 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
  114. 114. management • anti-androgen withdrawal • addition of ant androgens • anti-androgen replacement • estrogenic compounds, • adrenolytic agents
  115. 115. • 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
  116. 116. Cytotoxic chemotherapy • Docetaxel containing CT-progress within 6 to8 months • So toxicity should balanced with benefit
  117. 117. ROLE OF RT • Conventional-four field box f/b boost to prostate and seminal vessicle-but rectal and bladder toxicities more
  118. 118. • 3 Dimensional Conformal techniques. • Multi-leaf collimators to “shape” fields • Reduced toxicities but no selective “sparing” possible
  119. 119. Intensity modulated Radiotherapy • Multiple non-coplanar beams -> • Inverse planning -> different • intensities -> highly conformal dose • distribution with normal tissue • sparing.
  120. 120. Image Guided RT (IGRT) • EPID, USG with Fiducial markers etc • Recently , CBCT-kV or MV , • Tomotherapy ,Cyberknife etc
  121. 121. Conformal RT • 3DCRTIMRT boost /IMRT alone
  122. 122. Respiratory motion • Superior –inferior-2.9+/-1.7 • Anterior-posterior-1.6+/-1.1
  123. 123. • ABS :monotherapy :T1c-T2a, GS<7,PSA≤10 • + EBRT : T≥2c, GS ≥7, PSA >10 • C/I :metastases, gross seminal vesicle J • involvement, large T3 disease.
  124. 124. Permanent seed implants • IODINE(I 125) & PALLADIUM (Pd 103 ) • Preplanned Transperineal • Implantation (Seattle Method) • TRUS guided • Intra-operative Planning Techniques • TRUS guided needle placement f/b intra-op • CT/MRI >Contouring > optimization > seeds. • LDR DOSE • Monotherapy : I-125 144 Gy; Pd-103 125 Gy. • After 40–50 Gy EBRT: I-125 110 Gy; Pd-103 90 Gy.
  125. 125. HDR-BRACHY • After loading catheters under trus guidence • I192 • After EBRT-9.5 GY-two fractions • Monotherapy-9.5GY bid X 2 days 10.5 gy X 3
  126. 126. LDR BRACHYTHERAPY HDR BRACHYTHERAPY
  127. 127. 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:5374%,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. •
  128. 128. • 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) •
  129. 129. • 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)
  130. 130. Treatment related toxicities
  131. 131. • 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
  132. 132. 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
  133. 133. 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.
  134. 134. Thank you
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