2/14/09. Why Discuss this topic? Managing Local Recurrences after Radiation Failure. PROSTATE CANCER Second Treatment

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1 Why Discuss this topic? Mack Roach III, MD Professor and Chair Radiation Oncology UCSF Managing Local Recurrences after Radiation Failure 1. ~15 to 75% of CaP pts recur after definitive RT. 2. Heterogeneous group of patients including: a) Those with slow failures b) Those with rapid failures c) Those with false positives post RT & RP 3. Local recurrences with/without regional or distant a) Suitable for local/regional salvage therapies? b) Suitable for following carefully PROSTATE CANCER Second Treatment Secondary Treatment After Radiation RP RT Cryo AD Percent < 12 mo. Lee et al. JCO 15: ,

2 Roach Salvage Prostatectomy INSTITUTION NO. PTS COMMENTS Duke ' % NED "old" Stanford ' NED, 55% Incont Mayo Clnic '92 14 "Stages" too high UCLA ' pretx PSA data Wayne State '94 13 PSAs too high Baylor ' % NED at 5 yrs Lee et al. JCO 15: , 1997 Mayo Clinic % DFS at 10 yrs. after XRT? Salvage Brachytherapy Permanent Brachytherapy as Salvage Treatment for Recurrent Prostate Cancer Beyer Urol 54: , pts : I Gy, /Pd Gy DFS = 67% PSA < or = 10 vs 25% DFS = 83% if low grade vs 30% high grade Incontinence 24% 2

3 Salvage Brachytherapy Salvage Brachytherapy for Localized Prostate Cancer After Radiotherapy Failure. Grado et al. J Urol 53: 2-10, pts : I125 /Pd-103 median fu 64.1 mo. 5 Year DFS = 34%, DSS = 79% 4% rectal ulcers, 6% incont. & persistent pain 2% colostomy Salvage Brachytherapy for Localized Prostate Cancer after Radiotherapy Failure Grado et al. Urology 53,1:1-10:1999 Actuarial biochemical disease-free survival. (n=49) Diease-Free Survival (%) % Cl Survival 95% Cl Months Magnetic resonance image-guided salvage brachytherapy after radiation in select men who initially presented with favorable-risk prostate cancer: a prospective phase 2 study Nguyen et al. Cancer 110: , 2007 BACKGROUND: The authors prospectively evaluated the late gastrointestinal (GI) and genitourinary (GU) toxicity and prostate-specific antigen (PSA) control of magnetic resonance imaging (MRI)-guided brachytherapy used as salvage for radiation therapy (RT) failure. 3

4 Magnetic resonance image-guided salvage brachytherapy after radiation in select men who initially presented with favorable-risk prostate cancer: a prospective phase 2 study Nguyen et al. Cancer 110: , 2007 METHODS: October , 25 men with a rising PSA and +Bx, at least 2 years post: EBRT (n=13) or brachytherapy (n=12) GS < or =7, PSA < 10 ng/ml, negative pelvic and bone imaging studies), Received MRI-guided salvage brachytherapy to a MPD of 137 gray on a phase 1/2 protocol. Magnetic resonance image-guided salvage brachytherapy after radiation in select men who initially presented with favorable-risk prostate cancer: a prospective phase 2 study Nguyen et al. Cancer 110: , 2007 RESULTS: Med fu 47 mos. the 4-yr est. of grade 3 or 4 GI or GU toxicity was 30% 13% of patients required a colostomy and/or urostomy to repair a fistula. An interval < 4.5 yrs between RT courses associated with a HR of 12 (p= 0.02) for grade 3 or 4 toxicity and 25 (p= 0.04) for colostomy and/or urostomy. Methods Feasibility of high-dose-rate brachytherapy salvage for local prostate cancer recurrence after radiotherapy: The University of California-San Francisco experience Brian Lee, Katsuto Shinohara, Vivian Weinberg, Alexander Gottschalk, Jean Pouliot, Mack Roach III, and I-Chow Hsu, Retrospectively evaluate salvage HDR for locally recurrent prostate ca after EBRT. Treated post primary EBRT for biopsy proven local recurrence and Negative mets w/u. All patients were treated with 36 Gy in 6 fractions using 2 HDR prostate implants, separated by 1 week. Eleven pts received NHT immediately pre-salvage. Primary outcomes: ASTRO definition. IJROBP 67: Methods Feasibility of high-dose-rate brachytherapy salvage for local prostate cancer recurrence after radiotherapy: The University of California-San Francisco experience Brian Lee, Katsuto Shinohara, Vivian Weinberg, Alexander Gottschalk, Jean Pouliot, Mack Roach III, I-Chow Hsu, Results: 89% 2 yr BNED 13 pts (>50%) achieved a PSA nadir </ =0.1 ng/ml, but others still declining. 2 PSA failures, (both PSA nadirs >/=1), and have subsequently been found to have distant metastases. 18 patients reported Grade 1 to 2 genitourinary symptoms by 3 months post salvage. 3 pts developed Grade 3 GU toxicity. Max observed GI tox was Grade 2; all cases spontaneously resolved. Conclusions: Salvage HDR prostate brachytherapy appears to be feasible and effective. IJROBP 67:

5 Salvage Permanent Perineal Radioactive Seed Implantation For The Treatment of Localized Prostate Adenocarcinoma Recurrence After External Beam Radiation David S. Aaronson, Ichiro Yamasaki, Alexander Gottschalk, Joycelyn Speight, I-Chow Hsu, Barby Pickett, Mack Roach III, Katsuto Shinohara Retrospective single institution cross-sectional design. Inclusion/Exclusion: Treated with primary EBRT for biopsy proven local recurrence 2 yrs after initial Tx Negative metastat w/u. Primary outcomes: biochemical relapse free survival (Phoenix definition). Methods (In Press BJU 2009) Methods Salvage Permanent Perineal Radioactive Seed Implantation For The Treatment of Localized Prostate Adenocarcinoma Recurrence After External Beam Radiation David S. Aaronson, Ichiro Yamasaki, Alexander Gottschalk, Joycelyn Speight, I-Chow Hsu, Barby Pickett, Mack Roach III, Katsuto Shinohara Secondary outcomes: IPSS IIEF Complications: Common Terminology Criteria for Adverse Events (version 3). Pre-planned I-125 or Pd-103 radioactive seeds transperineally placed using ultrasound guidance. (In Press BJU 2009) Results Patient Characteristics Table 1. Clinical Characteristics of the Study Cohort Prior to Salvage Therapy (N = 24) Characteristics No. of patients (%) Median age at salvage therapy [range], 66 (54-88) Median initial PSA [range], ng/ml 9.9 [3.2-69] 0 to < 4 2 (8) 4 to < (46) >10 10 (42) Unknown 1 (4) Initial Gleason score 3+3 = 6 9 (38) 3+4 = 7 2 (8) 4+3 = 7 6 (25) 4+4 = 8 2 (8) 4+5 = 9 1 (4) Unknown 4 (16) Initial clinical tumor (T) classification T1c 11 (46) T2 11(46) Unknown 2 (8) Initial RT received EBRT ( Gy) 23 (96) EBRT+Ir192 LDR 1 (4) Median interval between EBRT [range], 4.4years [ ] < 2 0 (0) 2 to < 5 15 (62) >5 9 (38) Median PSA at salvage [range], ng/ml 3.41 [0.3-10] 0 to < 4 17 (71) 4 to < 10 6 (25) >10 1 (4) Results: PSA control & Survival Table 2: Cancer specific survival and biochemical relapse free survival. Cancer specific death: 1(4%) *Biochemical failure: 3(12%) *Definition: PSA nadir ng/ml Biochemical relapse free survival 1 year (n=17): 95.5% 2 years (n=10): 89.5% 3 years (n=6): 89.5% *PSA indicates prostate specific antigen; EBRT, external beam radiation therapy; Gy, grays 5

6 Results Results Results: Survival Results: Last PSA at follow-up Frequency 60% 50% 40% 30% 20% 50% 21% 17% 13% 10% < >0.5 on hormones PSA range Results-Complications Complication Rates, Common Terminology Criteria for Adverse Events (version 3) Complication Grade Hematochezia Grade 1: 2, after 17 mos Grade 3: 1, after 17 mos Hematuria Grade 2: 5, after 9 mos (med) Urethral Stricture Grade 2: 1, after 15 mos Urinary Incontin Grade 2: 1 6

7 MRSI Imaging after Brachytherapy Example of poorly covered apex MRSI Imaging after Brachytherapy Example of poorly covered apex 7

8 Pre-Salvage MRSI Imaging & CT Post Brachytherapy Example of poorly covered apex Conclusions At UCSF to date we have found that with careful pt selection and planning salvage brachytherapy has a high early control rate and acceptable toxicity Only Centers with sophisticated imaging and planning expertise should consider this option? Acknowledgements David S. Aaronson M.D. Ichiro Yamasaki M.D. Alexander Gottschalk M.D. Joycelyn Speight M.D. I-Chow Hsu M.D. Barby Pickett Katsuto Shinohara M.D. Brian Lee M.D., PhD Vivian Weinberg PhD John Kurhanewicz PhD 8

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