MANAGEMENT OF CARCINOMA
PROSTATE
Reference :
1) NCCN 2022
2) Perez and Brady’s principles and practice of
Radiation Oncology 7th edition
Risk Stratification
Very Low Risk
• Expected Patient survival:
More than 20 years :
• Active Surveillance ( Preferred)
• Radiation Therapy
• Radical Prostatectomy
Very Low Risk
• Expected Patient survival:
More than 10-20 years :
Active Surveillance
• Expected Patient survival:
Less than 10 years :
Observation
Low Risk
• Expected Patient survival:
More than 10 years :
• Active Surveillance ( Preferred)
• Radiation Therapy
• Radical Prostatectomy
Less than 10 years:
Observation
INTERMEDIATE RISK
IRF : Intermediate Risk factor
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
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
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
UNFAVOURABLE INTERMEDIATE
RADICAL PROSTATECTOMY
• Based on SPCG-4 & PIVOT Trial  RP is a recommended treatment
option if life expectance is >=10 years.
HIGH & very RISK GROUP
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
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
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
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 .
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.
• 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 .
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.
HIGH and VERY HIGH RISK
• Prophylactic nodal radiation –considered.
• ADT is given unless contraindicated.
• Brachytherapy + ADT / SBRT +ADT can be used .
DOSE ESCALATION
HYPOFRACTIONATION
ADJUVANT RADIATION THERAPY
• Treatment is individualized based on age/ co-morbidities /clinical and
pathological information , PSA level and PSADT.
• Molecular 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 .
INDICATIONS- Adjuvant RT
• Positive surgical margins
• Seminal vesicle invasion
• Extracapsular extension
• LN mets
• Poorly diffrentiated adenocarcinoma
• GS 8-10
• pT3 disease.
BRACHYTHERAPY
As per NCCN –
• Recommended only in low-risk or favorable intermediate
risk( MONOTHERAPY)
• Unfavorable intermediate risk – EBRT + BT +/- Androgen
Deprivation therapy – Based on ASCENDE-RT trial
• High risk – Dose Escalation – Highly beneficial.
HDR Brachytherapy –Absolute and radiobiological dose escalation –
high tumor 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%
CONTRAINDICATIONS
SEEDS AND IMPLANTATION
PERMANENT
• Iodine 125
• Palladium 103
• Cesium 131
TEMPORARY
• Iridium 192
• Cesium 137
ANDROGEN DEPRIVATION THERAPY
• 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
• 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
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
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
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
FOLLOW UP SCHEDULE
• First follow-up : 3 months
• Years 0–1 : Every 3 –4 months
• Years 2–5 : Every 6 months
• Years 5+ : Annually

Carcinoma Prostate

  • 1.
    MANAGEMENT OF CARCINOMA PROSTATE Reference: 1) NCCN 2022 2) Perez and Brady’s principles and practice of Radiation Oncology 7th edition
  • 4.
  • 5.
    Very Low Risk •Expected Patient survival: More than 20 years : • Active Surveillance ( Preferred) • Radiation Therapy • Radical Prostatectomy
  • 6.
    Very Low Risk •Expected Patient survival: More than 10-20 years : Active Surveillance • Expected Patient survival: Less than 10 years : Observation
  • 7.
    Low Risk • ExpectedPatient survival: More than 10 years : • Active Surveillance ( Preferred) • Radiation Therapy • Radical Prostatectomy Less than 10 years: Observation
  • 8.
  • 9.
    IRF : IntermediateRisk factor
  • 10.
    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
  • 11.
    ACTIVE SURVEILLANCE • Basedon ProtecT trial • Multiparametric MRI &/ or Prostate Biopsy &/or Molecular tumour analysis. • PSA – 6 monthly once • DRE – Annually • Repeat Biopsy –Annually • Repeat MRI – Annually
  • 12.
    OBSERVATION • Involves monitoringthe 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
  • 14.
  • 15.
    RADICAL PROSTATECTOMY • Basedon SPCG-4 & PIVOT Trial  RP is a recommended treatment option if life expectance is >=10 years.
  • 16.
    HIGH & veryRISK GROUP
  • 17.
    Clinical and PathologicalFeatures (HIGH) • Has no very high risk features and has atleast one high risk feature: T3a Grade group-4 / 5 PSA >20 ng/ml
  • 18.
    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
  • 19.
    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
  • 21.
    RADIATION TECHNIQUES • Highlyconformal 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 .
  • 22.
    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.
  • 23.
    • Additionally, theuse 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 .
  • 24.
    DEFINITIVE RT Favorable IntermediateRisk • 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.
  • 25.
    HIGH and VERYHIGH RISK • Prophylactic nodal radiation –considered. • ADT is given unless contraindicated. • Brachytherapy + ADT / SBRT +ADT can be used .
  • 26.
  • 27.
  • 28.
    ADJUVANT RADIATION THERAPY •Treatment is individualized based on age/ co-morbidities /clinical and pathological information , PSA level and PSADT. • Molecular 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 .
  • 29.
    INDICATIONS- Adjuvant RT •Positive surgical margins • Seminal vesicle invasion • Extracapsular extension • LN mets • Poorly diffrentiated adenocarcinoma • GS 8-10 • pT3 disease.
  • 30.
    BRACHYTHERAPY As per NCCN– • Recommended only in low-risk or favorable intermediate risk( MONOTHERAPY) • Unfavorable intermediate risk – EBRT + BT +/- Androgen Deprivation therapy – Based on ASCENDE-RT trial • High risk – Dose Escalation – Highly beneficial.
  • 31.
    HDR Brachytherapy –Absoluteand radiobiological dose escalation – high tumor 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%
  • 34.
  • 35.
    SEEDS AND IMPLANTATION PERMANENT •Iodine 125 • Palladium 103 • Cesium 131 TEMPORARY • Iridium 192 • Cesium 137
  • 36.
  • 37.
    • ADT actsby 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
  • 38.
    • Prolongs survivalin selected patients. LHRH Agonist alone Goserelin , Histrelin , Leuprolide or Triptorelin . LHRH Agonist + First generation Antiandrogen Nilutamide, Flutamide or Bicalutamide LHRH Antagonist Degarelix
  • 40.
    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
  • 41.
    CASTRATION RESISTANT PROSTATECANCER 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
  • 42.
    Second Line HormonalTherapy 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
  • 43.
    FOLLOW UP SCHEDULE •First follow-up : 3 months • Years 0–1 : Every 3 –4 months • Years 2–5 : Every 6 months • Years 5+ : Annually