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Post-operative Radiation Therapy following Radical Prostatectomy for Prostate Cancer. Stephen Ko, M.D. Mayo Clinic Jacksonville. Prostate Cancer. One third of patients undergo radical prostatectomy as initial therapy

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post operative radiation therapy following radical prostatectomy for prostate cancer

Post-operative Radiation Therapy following Radical Prostatectomy for Prostate Cancer

Stephen Ko, M.D.

Mayo Clinic Jacksonville

prostate cancer
Prostate Cancer
  • One third of patients undergo radical prostatectomy as initial therapy
  • 25-33% of patients are at risk of treatment failure following radical prostatectomy
  • 60-70% will develop metastatic disease within 10 years without further treatment
post operative radiation therapy following radical prostatectomy
Post-operative Radiation Therapy following Radical Prostatectomy
  • Adjuvant radiotherapy – presence of adverse factors – undetectable PSA
  • Salvage Radiotherapy – rising PSA
  • Salvage Radiotherapy – clinically apparent recurrent tumor in the prostatic fossa
adjuvant radiation therapy rationale
Adjuvant Radiation Therapy Rationale
  • Residual disease in the prostatic fossa is the primary cause of treatment failure
  • A substantial number of cells may be present before PSA is detectable
  • Greatest opportunity for cure exists when the cells are fewest in number and localized
adjuvant radiation therapy pathologic indications
Adjuvant Radiation Therapy Pathologic Indications
  • Extraprostatic extension
  • Seminal Vesicle invasion
  • Positive Surgical Margins
adjuvant radiation therapy prospective randomized clinical trials
Adjuvant Radiation Therapy Prospective Randomized Clinical Trials

Study No. Years Patients

SWOG 8794 1988-1997 425

EORTC 22911 1992-2001 1005

ARO 9602 1997-2004 268

adjuvant radiation therapy results
Adjuvant Radiation TherapyResults

*Statistically significant with RT

All numbers are in percentages

adjuvant radiation therapy results11
Adjuvant Radiation TherapyResults

*Statistically significant with RT

All numbers are in percentages

post operative radiation therapy following radical prostatectomy13
Post-operative Radiation Therapy following Radical Prostatectomy
  • Adjuvant radiotherapy – presence of adverse factors – undetectable PSA
  • Salvage Radiotherapy – rising PSA
  • Salvage Radiotherapy – clinically apparent recurrent tumor in the prostatic fossa
salvage radiotherapy
Salvage Radiotherapy
  • PSA Serum Half-Life = 3.1 days
  • PSA should be undetectable > 4 weeks after RP
  • Biochemical Relapse
    • AUA > 0.2, twice consecutively
    • Stephenson > 0.4, twice consecutively
radical prostatectomy biochemical relapse factors associated with metastatic disease and death
Radical Prostatectomy: Biochemical RelapseFactors Associated with Metastatic Disease and Death
  • Persistently elevated PSA after Prostatectomy
  • Shorter interval from surgery to biochemical relapse
  • Shorter PSA doubling time
  • Higher Gleason Scores
  • Higher GPSM Scores
  • Non-diploid tumor DNA
radical prostatectomy gpsm scoring algorithm
Radical Prostatectomy GPSM Scoring Algorithm

GPSM – Prostatectomy Gleason Score

+ 1 (Pre-op PSA 4-10)

+ 2 (Pre-op PSA 10.1-20)

+ 3 (Pre-op PSA >20)

+ 2 (+S.V. or +Nodes)

+ 2 (Positive Surgical Margins)

GPSM score of >10: Increased biochemical relapse; Increased risk of death

radical prostatectomy post op psa kinetics doubling time
Radical Prostatectomy:Post-op PSA kinetics (doubling time)
  • PSA Working Group Guidelines for PSAdt calculations
  • >3 PSA values which are >0.2 ng/ml and increasing within 12 months
  • Stable testosterone levels (not recovering from androgen suppression)
  • Relationship of PSAdt clinical relapse and mortality – continuum
radical prostatectomy psa doubling time
Radical Prostatectomy:PSA doubling time
  • Strongly associated with clinical relapse
  • PSAdt <3 months: Short life expectancy
  • PSAdt <12 months: 50-75% of patients with clinical relapse within 10 years
  • PSAdt <15 months: 90% deaths due to prostate cancer
  • PSAdt >15 months: 33% deaths due to prostate cancer
radical prostatectomy biochemical relapse
Radical Prostatectomy:Biochemical Relapse
  • Abnormal CT is rare with:
    • PSA < 5-10 ng/ml
    • PSAdt > 6-10 months
  • Abnormal bone scan is rare with:
    • PSA < 10 ng/ml
radical prostatectomy biochemical relapse mri findings
Radical Prostatectomy:Biochemical Relapse – MRI findings

Sensitivity Specificity Accuracy

  • Endorectal MR 84-95% 89-100% 86-94%
  • Local Recurrence averaged 1.5 cm in diameter
  • Patients typically had PSA levels > 2 ng/ml
biochemical relapse mri sites of recurrence
Biochemical RelapseMRI sites of Recurrence
  • Vesicourethral anastomosis: 44%
  • Retrovesicle space: 30%
  • Seminal vesicle region: 23%
salvage prostate bed radiation therapy prognostic factors
Salvage Prostate Bed Radiation Therapy Prognostic Factors
  • Prostatectomy Gleason Score
  • Tumor DNA ploidy
  • Persistently detectable post-op PSA
  • PSA level before prostatectomy
  • PSAdt postoperatively
  • Surgical Margin status
  • Seminal vesicle invasion
  • Pelvic lymph node involvement
  • Delay in initiation of salvage RT
salvage prostate bed radiation therapy prognostic scoring systems
Salvage Prostate Bed Radiation Therapy Prognostic Scoring Systems
  • Stephenson Nomogram
  • Mayo Scoring System
mayo scoring system29
Mayo Scoring System

Points 5y BCR

0-1 69%

2 53%

3 26%

4-5 6%

salvage radiation therapy androgen suppression
Salvage Radiation Therapy +/- Androgen Suppression
  • RTOG 9601 – Prostate fossa
    • RT + placebo
    • RT + bicalutamide
  • RTOG 0534
    • Prostate fossa RT
    • Prostate fossa RT with androgen suppression
    • Prostate fossa + Node RT with androgen suppression
  • Japan Clinical Oncology Group 0401
    • Prostate fossa RT
    • Prostate fossa RT + bicalutamide
  • Medical Research Council PR 10
    • Prostate fossa RT
    • Prostate fossa RT + 6 months androgen suppression
    • Prostate fossa RT + 2 years androgen suppression
salvage radiation therapy consensus based guidelines
Salvage Radiation TherapyConsensus Based Guidelines
  • Organizations which support offering salvage RT to all men with a detectable PSA
    • NCCN
    • European Association of Urology
    • European Society of Medical Oncology
    • Australian and New Zealand Radiation Oncology Genito-Urinary Group
post operative radiation therapy following radical prostatectomy35
Post-operative Radiation Therapy following Radical Prostatectomy
  • Adjuvant radiotherapy – presence of adverse factors – undetectable PSA
  • Salvage Radiotherapy – rising PSA
  • Salvage Radiotherapy – clinically apparent recurrent tumor in the prostatic fossa
post op prostate bed radiation therapy adverse effects
Post-op Prostate Bed Radiation Therapy Adverse Effects
  • Early: During RT or within 90 days of RT completion
  • Late: Effects which occur or persist after 90 days of RT completion
post op prostate bed radiation therapy adverse effects42
Post-op Prostate Bed Radiation Therapy Adverse Effects
  • Prognostic Factors
    • Antecedent Surgery
    • RT Treatment Planning
    • RT Treatment Techniques
    • RT Dose Volumetric Perimeters
    • Imaging and localization methods
post op prostate bed radiation therapy early adverse effects
Post-op Prostate Bed Radiation Therapy Early Adverse Effects
  • Dysuria
  • Urgency/Frequency
  • Proctalgia
  • Increased daily stools
  • Hematochezia
post op prostate bed radiation therapy early adverse effects44
Post-op Prostate Bed Radiation Therapy Early Adverse Effects
  • Prognostic Factors
    • Rectal dose
    • Pelvic nodal RT
    • Diabetes Mellitus
    • Hemorrhoids
    • Androgen Suppression
    • Anticoagulant Use
post op prostate bed radiation therapy late adverse effects
Post-op Prostate Bed Radiation Therapy Late Adverse Effects
  • Late grade >2 adverse events is <20% at 5 years
  • Prevalence is considerably less as many adverse events are not chronic
  • Severe events are <1%
post op prostate bed radiation therapy late adverse gi effects
Post-op Prostate Bed Radiation Therapy Late Adverse GI Effects
  • Increased or urgent stools/tenesmus
  • Proctalgia
  • Hematochezia
  • Mucous discharge
  • Rectal stricture
  • Fecal incontinence (0.2%)
  • Five-year incidence of >2 GI events is <5%
  • Severe GI events are uncommon <1%
post op prostate bed radiation therapy late adverse gu effects
Post-op Prostate Bed Radiation Therapy Late Adverse GU Effects
  • Difficult to accurately attribute late GU effects causality because both surgery and RT contribute
  • Incidence of grade >2 late effects is approximately 10%
  • Bladder Neck Contracture
  • Urethral stricture 5%
  • Dysuria
  • Transient hemturia (5%)
post op prostate bed radiation therapy late adverse gu effects48
Post-op Prostate Bed Radiation Therapy Late Adverse GU Effects
  • Urinary incontinence is comparable to surgery alone
  • If urinary incontinence occurs, it is typically of mild, stress-induced nature
  • RT does not appear to diminish erectile dysfunction in men who undergo nerve-sparing prostatectomy
post op prostate bed radiation therapy late side effects
Post-op Prostate Bed Radiation Therapy –Late Side Effects
  • Mayo Clinic Jacksonville
  • Retrospectively reviewed 308 patients who received salvage radiation therapy for a detectable PSA after prostatectomy
    • Aim: Evaluate the nature and severity of late GI and GU toxicity associated with salvage radiation therapy
post op prostate bed radiation therapy late side effects50
Post-op Prostate Bed Radiation Therapy –Late Side Effects

Mayo Clinic Jacksonville

  • GU toxicity
    • Grade 2: 7.7%
    • Grade 3-4: 1%
      • Included 3 patients with cystitis
    • 14 of 18 patients who developed urethral strictures required dilatation
    • 3.4% of patients had worsening urinary control
post op prostate bed radiation therapy late side effects51
Post-op Prostate Bed Radiation Therapy –Late Side Effects

Mayo Clinic Jacksonville

  • GI toxicity
    • Grade 2: 1.3%
    • Grade 3-4: 0.3%
      • Included one patient that required a diverting colostomy
post op prostate bed patient reported quality of life
Post-op Prostate Bed Patient Reported Quality of Life
  • Pinkawa et al. (Modern salvage RT technology)
    • Reduced urinary frequency and bother only at end of RT
    • Reduced bowel function and bother was reported through 2 months, but not thereafter