Presentation on theme: "How safe and effective is modern salvage radical prostatectomy?"— Presentation transcript:
1 How safe and effective is modern salvage radical prostatectomy? Surgical Treatment for Local Recurrence of Prostate Cancer After RadiotherapyHow safe and effective is modern salvage radical prostatectomy?Karim Touijer, MD., James A. Eastham, MDPeter T. Scardino, MDMemorial Sloan-Kettering Cancer CenterNew York
2 A Multi-institutional Pooled Analysis of Radiation Therapy For Clinically Localized Prostate CancerShipley, JAMA 281:1598, 1999
3 Without Salvage Therapy Biochemical recurrence distant metastasesPost-irradiation patients at high risk of metastases:Rapid PSA doubling timeHigh grade tumors3 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, 1998Pollack et al IJROBP 54: 677, 2002In case of rising PSA after EBRT with negative metastatic evaluation: 60% to 72% local persistence of disease on biopsyZagars et al IJROBP 33: 23, 1995
5 Definition of Local Recurrence Cancer in a needle biopsy >2 yr after radiotherapy in a patient with a rising PSA.CautionDifficult 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 prostatectomyCystoprostatectomy with urinary diversionCryotherapyInvestigational 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 morbidityDoubts 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 M0Current 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 yearsHighly 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) Median age at RP (range)65.4 ( )Median PSA at RP (range)6.3 ( )Median time from RT to RP (range), months48.1 ( )Pre-RP clinical stage: 1992 TNMT1c27T2a12T2b29T2c23T3a9Pre-RP biopsy Gleason sumGleason 2-633Gleason 742Gleason 8-1016Radiation treatment effect
15 Follow upThe median follow-up after radiotherapy and salvage RP was 10 years (range, 3 to 24 years) and 5 years (range, 1 to 20 years), respectivelyThe median time between radiation and surgery was 4 years41 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 P-valueMean Operative Time, hours4.43.70.001Mean Estimated Blood Loss, mL91010350.19Mean Length of Stay, days9.6<
18 RECOVERY OF CONTINENCE BY YEAR P = .335-yr Recovery67% (49-84)45% (26-64)
19 SEVERE URINARY CONTINENCE 23 patients required insertion of artificial urinary sphincter for severe incontinenceSphincter insertion rate did not improve over time (P= .92)Good outcome after sphincter placement, only one patient required revision procedure
20 * Defined as erections satisfactory for intercourse RECOVERY OF POTENCY*Patients Evaluated66Median age, years65.8Potent preoperatively24 (36)NVB preservationBilateral7 (11)Unilateral17 (25)Nerve grafts8 (12)10 (15)5-yr Recovery: 16% (4-28%)* Defined as erections satisfactory for intercourse+/- sildenafil
21 RECOVERY OF ERECTIONS BY PREOPERATIVE POTENCY STATUS At Risk
22 RECOVERY OF POTENCY 5-Year Potency (95% CI) Overall (n=66) 16% (4-28%) Bilateral (n=7) or Unilateral NVB (n= 17) Preservation28% (2-54%)Potent Preoperatively (n=24)45% (16-75%)5 of 7 patients (71%) who had bilateral nerve-sparing salvage RP are potentNerve 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 YearsNone received adjuvant treatment before relapse5-year PFP: 57%10-year PFP: 38%15-year-PFP: 29%Follow-up, median 9-yrs (1-19)
24 Pathologic Outcomes after Salvage RP OverallN=100N=48N=52P-valueOrgan-confined32%17%46%0.002Extraprostatic extension45%67%25%0.005Seminal vesicle invasion38%50%27%0.03Positive surgical margin29%31%8%0.004Positive lymph nodes9%4%14%0.02
25 Long term cancer control: Standard versus salvage RP Standard RRP*Salvage RRPPFP:5-year10-yearOrgan Confined94.9%92.2%86.0%ECE76.3%71.4%61.6%41.0%SVI37.4%47.6%32.6%LN +18.5%7.4%60.0%-N=1,000N=100*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 Progression by Preoperative PSA level <4 vs. >4 and <10 vs. >10 ng/mLLog-Rank Test:1 vs. 2: p= 0.021 vs. 3: p= 0.0142 vs. 3: p= 0.791. PSA <4 ng/mL3. PSA >10 ng/mL2. PSA >4 & <10ng/mLN=32N=30N=26N=9N=3N=13N=5N=2N=6
28 Cancer Specific Survival Median follow up from surgery 5 years (1 – 20)
29 Cancer Specific Survival after Salvage RP: Preoperative Serum PSA
30 Lessons LearnedModern 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, stricturesLong lag time between radiotherapy and salvage RP leads to high recurrence rate despite restricting surgical candidates to those with PSA <10 ng/mL.