Download
post operative radiation therapy following radical prostatectomy for prostate cancer n.
Skip this Video
Loading SlideShow in 5 Seconds..
Post-operative Radiation Therapy following Radical Prostatectomy for Prostate Cancer PowerPoint Presentation
Download Presentation
Post-operative Radiation Therapy following Radical Prostatectomy for Prostate Cancer

Post-operative Radiation Therapy following Radical Prostatectomy for Prostate Cancer

1171 Views Download Presentation
Download Presentation

Post-operative Radiation Therapy following Radical Prostatectomy for Prostate Cancer

- - - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript

  1. Post-operative Radiation Therapy following Radical Prostatectomy for Prostate Cancer Stephen Ko, M.D. Mayo Clinic Jacksonville

  2. 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

  3. 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

  4. 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

  5. Adjuvant Radiation Therapy Declining in Utilization 12% 1998-2000 7% 2004-2005

  6. Adjuvant Radiation Therapy Pathologic Indications • Extraprostatic extension • Seminal Vesicle invasion • Positive Surgical Margins

  7. 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

  8. Adjuvant Radiation TherapyEligibility

  9. Adjuvant Radiation TherapyEndpoints

  10. Adjuvant Radiation TherapyResults *Statistically significant with RT All numbers are in percentages

  11. Adjuvant Radiation TherapyResults *Statistically significant with RT All numbers are in percentages

  12. Radical Prostatectomy Adjuvant Androgen Suppression

  13. 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

  14. 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

  15. 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

  16. 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

  17. GPSM Scoring Outcomes

  18. 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

  19. 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

  20. 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

  21. 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

  22. Biochemical RelapseMRI sites of Recurrence • Vesicourethral anastomosis: 44% • Retrovesicle space: 30% • Seminal vesicle region: 23%

  23. Biochemical Relapse:Salvage Prostate Bed Radiation Therapy Results

  24. 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

  25. Salvage Prostate Bed Radiation Therapy Prognostic Scoring Systems • Stephenson Nomogram • Mayo Scoring System

  26. Stephenson Nomogram

  27. Stephenson Algorithm

  28. Mayo Scoring System

  29. Mayo Scoring System Points 5y BCR 0-1 69% 2 53% 3 26% 4-5 6%

  30. Dose Response Analysis

  31. Dose Response PSA <0.6

  32. Dose Response >0.6

  33. 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

  34. 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

  35. 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

  36. Radical ProstatectomyClinically-Apparent Local Recurrence

  37. RTOG guidelines salvage RT

  38. Positive apical margin + bCR

  39. ECE + SVI

  40. Dose Constraints

  41. 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

  42. 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

  43. Post-op Prostate Bed Radiation Therapy Early Adverse Effects • Dysuria • Urgency/Frequency • Proctalgia • Increased daily stools • Hematochezia

  44. Post-op Prostate Bed Radiation Therapy Early Adverse Effects • Prognostic Factors • Rectal dose • Pelvic nodal RT • Diabetes Mellitus • Hemorrhoids • Androgen Suppression • Anticoagulant Use

  45. 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%

  46. 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%

  47. 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%)

  48. 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

  49. 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

  50. 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