Salvage Radical Prostatectomy RJ Karnes MD FACS ViceChair

Salvage Radical Prostatectomy RJ Karnes MD, FACS Vice-Chair Associate Professor and Consultant Dept. of Urology/Urologic Oncology Mayo Clinic-Rochester

Professor Horst Zincke 1937 -2011 "He was a man, take him for all in all, I shall not look upon his like again. "

Radiation Recurrence? • Most radiation failures treated with “palliative” hormonal therapy (HT) • CAPSURE: 63% treated - recurrent or • secondary treatment at mean f/u of 38 months (93% HT) Long-term HT not without side effects • Agarwal, Cancer, 2008 • Better definition? • ASTRO: 2 ng/ml >from nadir; predictive of progression not local recurrence • Nadir PSA above 1 or 1. 5 ng/ml-probably worrisome?

Local Recurrence: Chance for Cure? • EORTC Bolla trial= ~20% LR only (EBRT and EBRT + ADT) • Lancet Oncology 2010 • Even at dosages to 78 Gy almost 1/3 will have a positive biopsy at 2 years • Predictive of progression compared to negative biopsy • Crook J • Late wave of metastasis from local persistence • Coen et al, Shipley, JCO 2002

My workup • Radiographic imaging: • CT scan • Bone scan • Endorectal coil MRI (3 Tesla) • Investigational: 11 C-choline PET/CT scan (PPV >95%)

CT Scan

MRI-Endorectal coil

My workup (after “OK” imaging) Standard 12 core TRUS prostate biopsy including 2 cores of SVs (seminal vesicles) • Severe treatment effect= Behave like – • Wait at least 12 -24 months • Office flexible cystoscopy (anatomy, high risk disease, secondary bladder cancer) • Rare-Urodynamic study • Colonoscopy within 5 years • Stoma counseling/marking/enema bowel prep

Pattern of Spread: Importance of Seminal Vesicles • Sanctuary

Brachytherapy Failures Treated by Surgery n=9 • All specimens whole mounted and stepsectioned • Iodine or Palladium seeds collected and counted

Benign Cancer

Rt SV • Prostate map created for each specimen R Lt SV P A A P P P A A Base L A = Anterior P = Posterior Apex 33 Seeds Gleason 4+3 Tx Vol=12. 5 cc p. T 3 b. N 0

Results

Results 5 Seminal Vesicle Involvement (n=6) Count 4 3 2 1 0 T 2 a. N 0 T 2 b. N 0 T 3 a. N 0 T 3 b. N 1 T 4 Nx Pathologic Stage Importance of Seminal Vesicles!

Kill Zone Seed

Kill Zone Cancer “Re-Growth” Seed

Oncologic Outcomes

“Ideal” Surgical Candidate…. not unlike radiation naive • >10 year life expectancy • Coping skills • PSA < 10 ng/ml • Lower Gleason score (non 8 -10) • c. T 1 -T 2 • c. N • However I do not rule out others…. .

Mayo Clinic • Before 2000, Largest series n=108 (106 EBRT), `66 -`96 • p. T 2 39%, p. Tx. N+ 18%, R 1 36% • 10 yr BCR(PSA)-free 34% • 10 yr Cancer specific survival (CSS) 70% • Amling, J Urol 1999 • Update to 2000, n=138 (127 EBRT), Median F/U 84 mths. Median age 65 yo • 10 yr CSS 77% • Ward, J Urol 2005

International Collaboration • Salvage Radical Prostatectomy (SRP)

Overall N=392 Interval between XRT and SRP (months) Year of SRP 1985 to 1994 1995 to 1999 2000 to 2004 2005 to 2009 Age at SRP (years) PSA before SRP (ng/ml), n=371 Biopsy Gleason before SRP ≤ 6 7 ≥ 8 Unknown/Not graded Clinical stage before SRP T 1 T 2 T 3 Unknown 41 (27, 58) 78 (20%) 73 (19%) 113 (29%) 128 (33%) 65 (60, 69) 5. 0 (2. 6, 8. 0) 109 (28%) 77 (20%) 97 (25%) 87 (22%) 166 (42%) 76 (19%) 63 (16%) Chade D, Eur Urol, 2011

Overall N=392 Pathology Gleason ≤ 6 7 ≥ 8 Unknown/Not graded R 1/SMS Negative Positive Unknown p. T 3 a/ECE No Yes Unknown p. T 3 b/SVI No Yes Unknown Lymph node status Not done/Negative Positive 54 (14%) 144 (37%) 99 (25%) 95 (24%) 294 (75%) 96 (24%) 2 (1%) 208 (53%) 181 (46%) 3 (1%) 270 (69%) 118 (30%) 4 (1%) 336 (86%) 56 (14%)

Results BCR Metastasis Death Number of events 186 62 37 Median follow up for event-free patients 5 -year event-free probability % 3. 6 4. 4 48 (95% CI 42, 53) 37 (95% CI 30, 43) 82 (95% CI 77, 86) 76 (95% CI 69, 81) 92 (95% CI 88, 95) 83 (95% CI 77, 88) 10 -year event-free probability %

Results • Low risk subgroup: biopsy Gleason score before SRP ≤ 7 and pre-SRP PSA ≤ 4 ng/ml • 96 pts (25%) • 35 pts BCR, 4 metastases, 1 death from PCa • BCR-free probability • 62% (95% CI 49%, 72%) at 5 years • 46% (95% CI 31%, 60%) at 10 years.

Multivariable Cox proportional hazards regression to evaluate predictors of biochemical recurrence and metastases following salvage prostatectomy. Outcome: biochemical recurrence Outcome: metastases Hazard Ratio 95% CI P Value Preoperative model (n=371) Log PSA before SRP (ng/ml) Biopsy Gleason before SRP ≤ 6 1. 19 1. 02, 1. 38 0. 028 1. 39 1. 07, 1. 81 0. 015 Reference 0. 006 Reference Referenc 0. 004 7 ≥ 8 Unknown/Not graded 1. 70 2. 20 1. 62 1. 10, 2. 64 1. 41, 3. 42 1. 06, 2. 47 2. 28 4. 74 2. 45 0. 88, 5. 95 1. 97, 11. 4 1. 02, 5. 86 Reference Referenc 1. 19 1. 14 0. 87 0. 78, 1. 83 0. 70, 1. 86 0. 49, 1. 55 1. 58 2. 03 0. 88 0. 60, 4. 10 0. 74, 5. 58 0. 23, 3. 31 Clinical stage before SRP T 1 T 2 T 3 Unknown 0. 6 0. 3

Multivariable Cox proportional hazards regression to evaluate predictors of biochemical recurrence and metastases following salvage prostatectomy. Outcome: biochemical recurrence Outcome: metastases Hazard Ratio 95% CI P Value Postoperative model (n=369) Log PSA before SRP (ng/ml) Pathology Gleason at SRP ≤ 6 1. 22 1. 05, 1. 42 0. 01 1. 57 1. 19, 2. 06 0. 001 Reference 0. 002 Reference 0. 001 7 ≥ 8 Unknown/Not graded 1. 54 2. 61 1. 55 0. 92, 2. 59 1. 53, 4. 44 0. 90, 2. 67 0. 73 2. 69 1. 06 0. 28, 1. 88 1. 11, 6. 49 0. 41, 2. 73 Extracapsular extension Seminal vesical invasion Lymph node involvement 1. 07 1. 29 0. 95 0. 76, 1. 49 0. 91, 1. 83 0. 64, 1. 40 1. 55 1. 21 1. 91 0. 85, 2. 84 0. 67, 2. 17 1. 07, 3. 41 0. 7 0. 15 0. 8 0. 15 0. 029

Functional Outcomes • Urinary Incontinence • 0 ppd= 21 -90% • Artificial Urinary Sphincter @ 6 mths/stabilization • Erectile Function • Pre-op EF=9 -50% • Sufficient for intercourse 0 -20% • Bladder neck contracture <10 -20% • Rectal injury <10%

Cryo does not treat LNI and SVI Pisters, J Urol, 2009

Surgical Technique: RP+EPLND • Catheter in for 3 weeks and assess with cystogram • 5 point anastomosis (2 -0 Monocryl) over 20 Fr catheter • Prepare perineum for possible Vest sutures

HIGH RISK PROSTATE CANCER SURGICAL TECHNIQUE: EXTENDED PELVIC NODE DISSECTION Spermatic Cord Common Iliac Hypogastric (Internal Iliac)

General Approach • EBRT only • Assess tissue/fat plane at bladder neck if developed then approach similar to radiation naïve, i. e. retrograde otherwise antegrade • Brachytherapy or Combined • Antegrade (take down bladder first) • Non-nerve sparing

Wide Local Excision Resection Rt NVB Beyond Prostate Apex Pararectal Fat

Wide Local Excision Rhabdosphincter Peri/Pararectal Fat

Wide Local Excision versus Bilateral Nerve Sparing Edge of pelvic fascia lateral to resected NVB Superior pedicle resected to tip of SV NVB preserved Superior pedicle preserved (pelvic plexus)

Wide Resection Specimen

Wide Local Excision versus Bilateral Nerve Sparing Resected NVB Superior pedicle resected to tip of SV NVB Superior pedicle preserved (pelvic plexus)

Conclusions • Importance of staging (p. T 3 b and p. Tx. N+) • Technically challenging • Reasonable morbidity? • Survival outcomes acceptable • Diagnose earlier? • Goal-Cure; Avoid long-term hormonal therapy