Introduction

Unfavorable intermediate-risk group

• >10y EPS
  • RP +/- PLND if prob. of LN meta >2%
  • EBRT + ADT (4-6mo)
  • EBRT + ADT (4-6mo) + brachytherapy boost

High- or very-high-risk group

• >5y EPS or symptomatic
  • EBRT + ADT (1.5~3y)
  • EBRT + ADT (1~3y)+ brachytherapy boost
  • EBRT + ADT (2y) + docetaxel 6 cycles (for very-high-risk only)
  • EBRT + ADT (2y) + abiraterone (for very-high-risk only)
  • RP + PLND

Favorable intermediate risk

Has all of the following:

• Has 1 intermediate risk factors (IRFs):
  • cT2b-cT2c
  • Grade group 2 or 3
  • PSA 10-20ng/mL
• Grade Group 1 or 2
• <50% Bx cores positive (eg, <6 of 12 cores)

• EPS 5-10y
• Observation
• EBRT or brachytherapy
• EPS >10y
• Active surveillance
• EBRT or brachytherapy
• RP ± PLND if predicted probability of LN(+) ?2%
• Adverse features and LN(-): EBRT ± ADT or Monitoring, consider early RT for detectable and rising PSA
• LN (+): ADT ± EBRT or Monitoring, consider early RT for detectable and rising PSA

Unfavorable intermediate risk

Has ?1 of the following:

• 2 or 3 IRFs
• Grade group 3
• ?50% Bx cores positive (eg, ?6 of 12 cores)

• EPS 5-10y
• Observation
• EBRT + ADT (4-6mo) or EBRT + brachytherapy ± ADT (4-6mon)
• EPS >10y
• EBRT + ADT (4-6mo) or EBRT + brachytherapy ± ADT (4-6mon)
• RP ± PLND if predicted probability of LN(+) ?2%
• Adverse features and LN(-): EBRT ± ADT or Monitoring, consider early RT for detectable and rising PSA
• LN (+): ADT ± EBRT or Monitoring, consider early for detectable and rising PSA

High risk

Has exactly 1 high-risk feature:

• cT3a
• Grade Group 4or 5
• PSA >20ng/mL

Very high risk

Has ?1 of the following:

• cT3b-cT4
• Primary gleason pattern 5
• 2 or 3 high-risk features
• More than 4 cores with Grade Group 4 or 5

Clinical presentation

Definitions of intermediate- and high-risk disease

Management of pelvic lymph nodal disease: the rationale and evidence

Regional risk group (Any T, N1, M0)

• Initial therapy
  • EBRT + ADT (2yr) +/- abiraterone
  • ADT +/- abiraterone
  • RP + PLND
    • No adverse features
    • Adverse feature(s) & N meta (-): EBRT +/- ADT
    • N meta (+): ADT +/- EBRT or monitoring

Radiation therapy techniques: regional and local

EBRT

• Dose
  • intermediate- & high- risk: >74Gy (in 2 Gy/fx)
• Node+ pts
  • EBRT+long-term AS confers an OS benefit

Brachytherapy

• LDR brachy alone
  • Not appropriate for high-risk Dz, but may be considered for highly selected pts with intermediate-risk Dz.
  • Worse 5-yr bPFS compared to RP and EBRT alone
• neoadj AS + LDR brachy
  • To cytoreduce large prostates. But failed to to show improvement in outcomes.
• Brachytherapy boost

Pelvic nodal RT

• – None showed a cancer control benefit

RT dose for low risk

• Standard course: 79.2Gy/1.8Gy per fx (44fxs), 78Gy/2Gy/fxx (39fxs)
• Hypofractionate: 70Gy/2.5Gy per fx (28fxs), 60Gy/3.0Gy pepr fx (20fs)
• SBRT: 36-40Gy in 5fxs of 7.25-8Gy, (swedish) 42.7 Gy in 7fxs of 6.1Gy
• Brachy
  • LDR: I-125 (145Gy), Pd-103(125Gy), Cs-131 (115Gy)
  • HDR (4fxs): Ir-192 (13.5 Gy x 2 implants or 9.5Gy BID x 2 implants)

Technical considerations for external beam radiation

Androgen deprivation therapy and RT: evidence and indications

• Usually started 2 mos prior to the start of EBRT.
• Generally prescribed for the 1st 2-4 wks with a GnRH analog.

Neoadj AS prior to RP

• decreased +margin and LN+ rates
• but since long-term bFS rates do not appear to be improved, it’s not commonly used.

Adj AS after RP

• in node+ Dz, immediate adj AS after RP improves OS.

Adj ADT after RT

• improved OS in those with a GS of 8-10

With dose-escalated RT

• Long-term ADT improved biochemical and overall survival.

Side effects (esp. bicalutamide)

• Breast tenderness, gynecomastia (50%)
• Loss of libido, diarrhea, hepatotoxicity

Sequencing, optimal timing, and duration of ADT and radiation therapy

Postoperative (after a radical prostatectomy) radiation therapy

Conclusions and recommendations