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Surgical Treatment for Local Recurrence of Prostate Cancer After Radiotherapy

Surgical Treatment for Local Recurrence of Prostate Cancer After Radiotherapy. How safe and effective is modern salvage radical prostatectomy? Karim Touijer, MD., James A. Eastham, MD Peter T. Scardino, MD Memorial Sloan-Kettering Cancer Center New York.

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Surgical Treatment for Local Recurrence of Prostate Cancer After Radiotherapy

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  1. Surgical Treatment for Local Recurrence of Prostate Cancer After Radiotherapy How safe and effective is modern salvage radical prostatectomy? Karim Touijer, MD., James A. Eastham, MD Peter T. Scardino, MD Memorial Sloan-Kettering Cancer Center New York

  2. A Multi-institutional Pooled Analysis of Radiation Therapy For Clinically Localized Prostate Cancer Shipley, JAMA 281:1598, 1999

  3. Without Salvage Therapy • Biochemical recurrence distant metastases • Post-irradiation patients at high risk of metastases: Rapid PSA doubling time High grade tumors 3 Years

  4. Rationale for Local Salvage Therapy • Positive prostate biopsy 2 years or more after EBRT ~ 30% to 50% • 32% after EBRT (78 Gy) Zelefsky et al IJROBP 41: 491, 1998 Pollack et al IJROBP 54: 677, 2002 • In case of rising PSA after EBRT with negative metastatic evaluation: 60% to 72% local persistence of disease on biopsy Zelefsky et al IJROBP 41: 491, 1998 Zagars et al IJROBP 33: 23, 1995

  5. Definition of Local Recurrence Cancer in a needle biopsy >2 yr after radiotherapyin a patient with a rising PSA. Caution • Difficult to distinguish radiation induced atypia from residual cancer with severe radiation changes. Gleason grading may be inaccurate unless there is abundant viable cancer. • PSA “bounce,” a temporary rise in PSA within the first 2-3 years after radiotherapy, may occur in 10-15% of patients. • With neoadjuvant androgen deprivation, PSA rise after cessation of hormonal therapy may occur before radiation-induced PSA nadir, resulting in a temporary rise in serum PSA.

  6. Management alternatives for local recurrence after radiotherapy • Expectant management (delayed hormonal therapy) • Androgen ablation (continuous or intermittent) • Salvage radical prostatectomy • Cystoprostatectomy with urinary diversion • Cryotherapy • Investigational techniques: hyperthermia (RITA, HIFU), gene therapy, photodynamic therapy.

  7. Salvage Radical Prostatectomy • 10-year PSA progression free probability = 30% - 43%. • 10-year cancer specific survival rates = 70% - 77% • Fewer than 500 cases reported

  8. Why is salvage radical prostatectomy not widely accepted? • High peri-operative morbidity • Doubts about long term efficacy

  9. Evaluation of candidates for salvage prostatectomy • Is the cancer potentially curable? • Is the patient appropriate? • Would the operation be safe?

  10. Evaluation for salvage prostatectomy • Is the cancer potentially curable? • Initial cancer (before radiation) surgically curable: T1-3a N0 M0 • Current cancer T1-3a, PSA < 10, no evidence of metastases: bone scan, CT or MRI of abdomen and pelvic LN, Prostascint monoclonal antibody or PET scan

  11. Evaluation for salvage prostatectomy • 2. Is the patient appropriate? • Good health, life expectancy >10 years • Highly motivated, willing to accept risks of salvage surgery

  12. Evaluation for salvage prostatectomy • 3. Would the operation be safe? • No evidence of radiation cystitis or proctitis

  13. Salvage RP in 100 consecutive patients • Between 1984 and 2003, 100 consecutive patients underwent salvage RP with curative intent for biopsy-confirmed, locally recurrent prostate cancer after external-beam radiotherapy or brachytherapy. • Disease progression after salvage RP was defined as a PSA level of 0.2 or greater or by the initiation of androgen-deprivation therapy (ADT). • Cancer mortality was attributed to patients with active clinical disease progression despite castration at time of death. • Cox logistic regression analysis evaluated pre- and postoperative predictors of these endpoints.

  14. Clinical Parameters in 100 Consecutive Patients (1985-2003)

  15. Follow up • The median follow-up after radiotherapy and salvage RP was 10 years (range, 3 to 24 years) and 5 years (range, 1 to 20 years), respectively • The median time between radiation and surgery was 4 years • 41 patients had preoperative PSA levels > 10 ng/mL, but the proportion of these patients has decreased significantly since 1993 (56% vs 13%, P=.001) • The median preoperative PSA doubling time was 13 months and 22 patients had a PSADT of 6 months or less.

  16. HOSPITALIZATION AND OPERATIVE DATA OF SALVAGE RP

  17. POSTOPERATIVE COMPLICATIONS OF SALVAGE RP

  18. RECOVERY OF CONTINENCE BY YEAR P = .33 1993-2003 1984-1992

  19. SEVERE URINARY CONTINENCE • 23 patients required insertion of artificial urinary sphincter for severe incontinence • Sphincter insertion rate did not improve over time (P= .92) • Good outcome after sphincter placement, only one patient required revision procedure

  20. RECOVERY OF POTENCY* 5-yr Recovery: 16% (4-28%) * Defined as erections satisfactory for intercourse +/- sildenafil 67 49 38 35 29 21

  21. RECOVERY OF ERECTIONS BY PREOPERATIVE POTENCY STATUS P < 0.0001 At Risk 24 18 13 12 7 4 40 30 24 22 20 16

  22. RECOVERY OF POTENCY • 5 of 7 patients (71%) who had bilateral nerve-sparing salvage RP are potent • Nerve grafting (n=18) was not associated with recovery of potency

  23. Progression Free Probability (PFP) after Salvage Radical Prostatectomy Median Time to PSA Failure after Surgery 6.1 Years None received adjuvant treatment before relapse 5-year PFP: 57% 10-year PFP: 38% 15-year-PFP: 29% Follow-up, median 9-yrs (1-19)

  24. Pathologic Outcomes after Salvage RP

  25. Long term cancer control:Standard versus salvage RP *Hull et al. J. Urol, 167: 528, 2002

  26. Cox logistic-regression (multivariable) analysis risk of risk factors for PSA progression after salvage radical prostatectomy

  27. Progression by Preoperative PSA level<4 vs. >4 and <10 vs. >10 ng/mL Log-Rank Test: 1 vs. 2: p= 0.02 1 vs. 3: p= 0.014 2 vs. 3: p= 0.79 1. PSA <4 ng/mL 3. PSA >10 ng/mL 2. PSA >4 & <10 ng/mL N=32 N=30 N=26 N=9 N=3 N=13 N=5 N=2 N=6

  28. Cancer Specific SurvivalMedian follow up from surgery 5 years (1 – 20)

  29. Cancer Specific Survival after Salvage RP:Preoperative Serum PSA

  30. Lessons Learned • Modern salvage radical prostatectomy is safe and major complications are much less common. • Long-term progression-free probability, by pathologic stage, is comparable to standard RP. • Continuing challenges: • High rate of incontinence, strictures • Long lag time between radiotherapy and salvage RP leads to high recurrence rate despite restricting surgical candidates to those with PSA <10 ng/mL.

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