CA PROSTATE int & high

1. MANAGEMENT OF
CARCINOMA PROSTATE
Reference :
1) NCCN
2) Perez and Brady’s principles and practice of
Radiation Oncology 7th edition

4. CLINICAL FEATURES
• Lower urinary tract symptoms - nocturia, urinary
frequency, urgency, decreased flow, incomplete
voiding, intermittent flow, or hesitancy and
occasionally erectile dysfunction .
• Bulky primary disease - urinary tract obstruction
or difficulty in passing stool or even bloody stool.
• With increasing PSA and Gleason score, the risk of
metastases increases.

5. • Metastatic spread is generally sequential,
proceeding from the prostate to the
periprostatic pelvic lymph nodes, but some
appear to spread directly to the common iliac
nodes and then to bone.
• Rarely, patients may present with renal failure,
lymphedema of the lower extremities, and
bone pain.

6. INTERMEDIATE RISK

8. FAVOURABLE
• Has all of the following :-
• 1 IRF
• Grade Group 1 / 2
• < 50 % Biopsy cores positive
UNFAVOURABLE
• Has 1 or more of the
following :-
• 2 or 3 IRF’s
• Grade group-3
• >= 50% Biopsy cores
positive.

9. FAVOURABLE INTERMEDIATE
Expected Survival >= 10 Years
• Active Surveillance
• EBRT / BT alone
• RP +/- PLND (If nodal
metastasis >=2 %)
Expected Survival <10 Years
• EBRT / BT Alone
• Observation

10. ACTIVE SURVEILLANCE
• Based on ProtecT trial
• Multiparametric MRI &/ or Prostate Biopsy &/or
Molecular tumour analysis.
• PSA – 6 monthly once
• DRE – Annually
• Repeat Biopsy –Annually
• Repeat MRI – Annually
(Unless clinically indicated not repeated )

11. OBSERVATION
• Involves monitoring the course of disease with
the intention to deliver palliative therapy for
symptoms or change in examination or PSA that
suggests that symptom is imminent.
• Selection of patients with indolent disease or
comorbidities that would impact the expected
survival is crucial

13. UNFAVOURABLE INTERMEDIATE

14. RADICAL PROSTATECTOMY
• Based on SPCG-4 & PIVOT Trial  RP is a
recommended treatment option if life
expectance is >=10 years.

17. HIGH & VERY RISK GROUP

18. Clinical and Pathological Features
(HIGH)
• Has no very high risk features and has atleast
one high risk feature:
T3a
Grade group-4 / 5
PSA >20 ng/ml

19. VERY HIGH RISK
• Has at least one of the following
T3b- T4
Primary Gleason pattern 5
2 – 3 high risk features
>4 cores with Grade 4 or 5

20. INITIAL THERAPY
Expected Survival >5 yrs / Symptomatic
• EBRT + ADT (1.5-3 yrs ) +/- Docetaxel (for very
high risk )
• EBRT + Brachytherapy + ADT (1-3 yrs)
• RP + PLND
Expected Survival <=5 yrs / Asymptomatic
• Observation
• ADT
• EBRT

22. • Undetectable PSA After RP / PSA Nadir after RT

25. RADIATION TECHNIQUES
• Highly conformal techniques should be used to
treat localized prostate cancer .
• Photon or Proton EBRT are highly effective.
• Accuracy of the treatment should be verified by
daily prostate localization with any of the
following :-
IGRT Using CT
USG
Implanted fiducials
Electromagnetic tracking / targeting .

26. IGRT
• Image-guided RT (IGRT) allows for the adjustment
of patient daily set up as well as the positional
correction of the radiation beams during radiation
delivery .
• A consequence of modern, high-conformality RT,
however, is the risk of a “geographic miss”.
• Geometric uncertainty include target delineation
error, patient setup uncertainty and target position
variation (both day-to-day interfraction motion and
intrafraction movement during the course of
treatment delivery

27. • Additionally, the use of IGRT allows for the
reduction of planning margins .
• Imaging methods :-
Non-radiation-based -ultrasound,
electromagnetic tracking, and MRI systems
integrated into the treatment room or
treatment machine.
 Radiation-based - static as well as real time
tracking, using either kV, MV, or hybrid
methods .

28. • intraprostatic radiopaque markers with daily in-
room imaging as this technique is low cost, is
easy to use, and provides limited interobserver
variability .
• Three radiopaque markers, such as gold seeds
or coils, are implanted into the periphery of the
prostate via a transrectal or transperineal
approach.
• The FMs remain stable within the prostate with
an average displacement of 1.01–2.8 mm

29. • The markers are a surrogate for the prostate
position and thus ensure that the prostate and
rectal interface is reproducibly identified even
with prostate rotation and deformation

31. DEFINITIVE RT
Favorable Intermediate
Risk
• Prophylactic lymph node RT ,
ADT is not performed
routinely unless there is
aggressive tumour behaviour.
Unfavorable
Intermediate
• Prophylactic Pelvic RT can
be given after assesment.
• ADT must be given unless
contraindicated.
• Duration of ADT can be
reduced if EBRT & BT is
administered.
• SBRT + ADT can be
administered.

32. HIGH and VERY HIGH RISK
• Prophylactic nodal radiation –considered.
• ADT is given unless contraindicated.
• Brachytherapy + ADT / SBRT +ADT can be
used .

33. DOSE ESCALATION

34. Conclusion
• This suggests that dose escalation alone
cannot replace hormones as a strategy to
improve cure, and that both may be necessary
in patients with intermediate- and high-risk
disease.

35. HYPOFRACTIONATION

36. ADJUVANT RT
SWOG-8794 randomly assigned 425 node-negative patients initially
treated with radical prostatectomy but found to have either PSM or
pT3 (ECE and/or SVI) disease to ART or observation.
Central pathology review was performed in 73% of patients, and
there was a 95% concordance with the community pathologist.
Ninety percent of patients had ECE or PSM.
Two-thirds of patients had a postoperative PSA <0.2 ng/mL.

37. RT consisted of 60 to 64 Gy.
Median PSA relapse-free survival was significantly longer with
ART (10.3 vs. 3.1 years; P <.001).
Updated results were recently published with a median follow-up of
12.6 years.
The 10-year distant metastasis-free survival (71% vs. 61%; HR
0.71; P = .016) and overall survival (74% vs. 66%; HR 0.72; P =
.023) were significantly improved with ART.
The median distant metastasis-free survival was prolonged from 12.9
to 14.7 years with ART, and overall survival from 13.3 to 15.2 years.

38. • As it stands, we have only retrospective data
that suggest that early salvage radiotherapy is
more effective than later salvage radiotherapy,
and this is likely due to reduced tumor
burden.
• Whether early salvage radiotherapy is as good
as adjuvant radiotherapy is unknown.

39. NODE POSITIVE
• In a subset analysis of RTOG-8531,
• 141 postoperative patients with histologically confirmed node-positive
disease were randomized to postoperative radiotherapy with
immediate or delayed hormonal therapy.
• In the immediate hormone arm, the hormones were commenced in the last
week of radiotherapy and continued indefinitely.
• This subgroup received 60 to 65 Gy (postprostatectomy) and 65 to 70 Gy
(radical treatment) with optional nodal irradiation.
• With a median follow-up of 6.5 years, updated results demonstrated that
immediate hormones improved 5-year biochemical progression-free
survival (54% vs. 10%; P <.0001).
• Multivariate analyses, immediate hormones was associated with improved
overall survival, biochemical PFS, distant metastasis-free survival.

40. • REGIONAL DISEASE
• Nodal irradiation must be given .
• Clinically Positive nodes must be dose escalated
as DVH parameters allow.
• ADT is required unless contraindicated .
• ABIRATERONE or fine particle Abiraterone can
be considered.

41. ADJUVANT RADIATION THERAPY
• Treatment is individualised based on age/ co-
morbidities /clinical and pathological information ,
PSA level and PSADT.
• Moloecular assay –if adverse features are present .
• Administered within 1 year of RP and after post-op
recovery is complete.
• Patients with positive margins may benefit the most
.

42. INDICATIONS
• Positive surgical margins
• Seminal vesicle invasion
• Extracapsular extension
• LN mets
• Poorly diffrentiated adenocarcinoma
• GS 8-10
• pT3 disease.

43. ADVANTAGES
• Increased local control
• Eradicating microscopic periprostatic disease
• Decreased distant mets
• Improved survival

44. SALVAGE RADIATION THERAPY
• Indications :- Undetectable PSA that becomes
subsequently detectable and increases on 2
measurements or a PSA that is persistantly
detectable after RP .
• Treatment is more effective when pre-treatment
PSA Is low and PSAdt is long .

45. RAVES TRIAL
SRT spares approximately half of men
from pelvic radiotherapy, and is
associated with significantly lower levels
of GU toxicity.

48. BRACHYTHERAPY
• As per NCCN –
• Recommended only in low-risk or favourable
intermediate risk( MONOTHERAPY)
• Unfavourable intermediate risk – EBRT + BT +/-
Androgen Deprivation therapy – Based on
ASCENDE-RT trial
• High risk – Dose Escalation – Highly beneficial.

50. • HDR Brachytherapy –Absolute and radiobiological
dose escalation – high tumour control and low
toxicity .
• Dose rate - >=12 Gy /h.
• Boost schedules vary from 9-15 Gy in a single
fraction to 26 Gy in 4 fractions .
• 5 year Biochemical disease control –
Low risk – 85-100 %
Intermediate – 83-98%
High risk – 51- 96%

51. • Patient Evaluation
• Sexual function assessment.
• Gastrointestinal / Rectal function assessment.
• Urinary function assessment .
• Serum PSA
• Biopsy and HPE report
• MRI / CT – With Endorectal coil is preferred for
extracapsular extension.
• Bone Scan

52. • PRIOR PROSTATE RADIATION
• HDR Monotherapy - Salvage treatment for local
failure after EBRT / Permanent Seed
Brachytherapy –Promising results in patients
who don’t fit the criteria for salvage
prostatectomy .

55. CONTRAINDICATIONS

56. SEEDS AND IMPLANTATION
 PERMANENT
• Iodine 125
• Palladium 103
• Cesium 131
 TEMPORARY
• Iridium 192
• Cesium 137

57. • APPROACHES :
Perineal approach-
• Needles are introduced above the anus and are
guided into the prostate with the index finger in
the rectum
 Suprapubic Cystotomy Approach-
• The needles are placed directly in the prostate
through the open bladder with a finger in rectum
guiding the placement
 Retropubic approach-
• This approach is used most extensively, though it’s
a more difficult procedure.

58. ANDROGEN DEPRIVATION THERAPY

59. • ADT acts by reducing the level of androgen
hormones, to prevent the prostate cancer cells from
growing
 INDICATIONS
• Intermediate unfavorable prostate cancer
• High risk and Very High Risk Prostate Cancer
• Metastatic Prostate Cancer
• In recurrence after RT or Surgery
• Most patients with T3 are, at the present time,
treated with NAHT followed by RT

60. • Prolongs survival in selected patients.
LHRH Agonist alone
Goserelin , Histrelin , Leuprolide or Triptorelin .
LHRH Agonist + First generation Antiandrogen
Nilutamide, Flutamide or Bicalutamide
LHRH Antagonist
Degarelix

62. TIMING OF ADT
• Intermediate Risk:
• NACT : 3 to 6 months + Concurrent +/- Adjuvant : 6
months
• High and Very High Risk :
NACT : 3 to 6 months + Concurrent +/- Adjuvant : 24
to 36 months
• Metastatic : Gold Standard for metastasis at time of
presentation

63. CASTRATION RESISTANT PROSTATE
CANCER
Defined by disease progression despite
androgen depletion therapy (ADT) and may
present as :
o Continuous rise in serum prostate-specific antigen
(PSA) levels
o Progression of pre-existing disease
o Appearance of new metastases

64. Second Line Hormonal Therapy
ABIRATERONE ACETATE:
• 1000MG DAILY(250 Mg 4 tabs daily)
• Taken with Prednisone 5mg BD
• FDA approved 1st line therapy in asymptomatic
CRPC
• 2nd line therapy after failure of docetaxel
ENZALUTAMIDE:
• Inhibits signaling of androgen receptor
• Poor PS
• Given with GNRH Agonists

66. FOLLOW UP SCHEDULE
• First follow-up : 3 months
• Years 0–1 : Every 3 –4 months
• Years 2–5 : Every 6 months
• Years 5+ : Annually