David Spellberg, M.D., FACS Naples Urology Associates, P.A.

Background Stanford prostate CK program initiated 12/03 Naples prostate CK program initiated 2/05 Both programs focused on low-risk patients: T1c-T2a disease; PSA < 10.0; Gleason score < 7 Stanford data initially published in spring of 2009 (IJROBP); updated 2010 Naples data published in fall of 2009 (TCRT)

PATIENT DRIVEN NON-INVASIVE MINIMAL SIDE EFFECTS MINIMAL DISRUPTION OF LIFE EFFICACY

Patient lies comfortably on the couch while the CyberKnife robot moves, images and corrections automatically for movement Treatments typically last mins per session Most patients require no sedation allowing them to depart at the completion of their treatment CyberKnife Treatment Delivery

Delivery of hundreds of radiation beams to the prostate Precise control limits of dose to the rectal wall and urethra Prostate Radiosurgery

Prostate PTV: gland expanded 5 mm in each direction except posteriorly where it is expanded 3 mm

SEQUENCE OF EVENTS PATHOLOGY REVIEW CT/BS REVIEW DISCUSSION OF TREATMENT OPTIONS FIDUCIAL PLACEMENT CYBERKNIFE TREATMENT

FIDUCIAL PLACEMENT NPO IV SEDATION TRUS GUIDED TEMPLATE ANTIBIOTICS

Collective experience 2/05-4/08 (Naples) 59 EBRT + CK boost 164 monotherapy, 35Gy 168 monotherapy, 36.25Gy 7/08-12/09 (Tampa) 50 monotherapy, 36.25Gy

Acute Toxicity Scoring (IPSS/RAS/SHIM) Baseline, days 2 and 5, post-treatment day 10, 1 month and 4 months Acute effects generally return to baseline by 1 months Urinary symptoms more marked in patients with IPSS baseline scores >20 No urethral strictures/ persistent rectal bleeding observed

Toxicity No RTOG grade 3 rectal toxicity One RTOG grade 3 urinary toxicity (dysuria) No incontinence reported RTOG Grade IIIIIIIV Urinary 25% (10/41) 7% (3/41) 2.5% (1/41) 0% Rectal 13% (6/41) 2.5% (1/41) 0%

PSA Response to CyberKnife 97% biochemical control at 30 months

Kaplan-Meier biochemical disease-free survival curve after SBRT for prostate cancer. Median follow-up is 5-years. Three of the 41 patients recurred, at 33, 37 and 42 months post-treatment. Tick marks indicate censored patients.

Disease recurrences 4 pts. with biopsy-confirmed local relapse 2 pts. at 24 months post-CK 2 pts. at 36+ months post-CK 1 pt. with distant relapse at 6 months; no local failure

Treatment comparison Treatment option 5 yr. bDFS Prostatectomy IMRT LDR brachy HDR brachy SBRT* 76-92% 69-89% 83-88% 90-92% 93% *current study

 Dysuria in 20% at 1 month  Dysuria in 10% at 2 months  Dysuria in <1% at 24 months  Dysuria in 25% at 1 month  Dysuria in 18% at 2 months  Dysuria in 2% at 24 months Dysuria  Urinary incontinence reported in <1% at any time period  20% continent on catheter removal  50% continent at 1 month  80% continent at 3 months  50-95% of urinary 2yrs  90-95% of urinary continence 5yrs Urinary Incontinence  1 st treatments performed 2003  1 st treatments performed in 2000  Significant change in technique in 2004/05 with use of nerve sparing procedures Treatment Experience  Excellent PSA Response 4years)  Excellent PSA Response 5 years) PSA Response  Rectal toxicity 10% at 1 month  Rectal toxicity <5% at 1 year  Rectal toxicity <3% at 1 month  Rectal toxicity <1% at 1 year Rectal Toxicity  % return of EF by 1 month  48-81% EF preserved at 2 years  No EF data available at 5 years yet  50% return of EF by 6-8 months  50-87% EF preserved at 2 yrs  79-87% EF preserved at 5 yrs Erectile Function CyberKnifeda Vinci Treatment Comparisons

Sexual Function Urinary Toxicity CyberKnife ® Lap Prostatectomy Treatment Comparisons

Erectile Function Of 76 pts. evaluable at 2 yrs, 81% maintained “erections sufficient for intercourse” (based on question #2 of SHIM)

Summary CyberKnife SRS produces a reasonable early decline of PSA in low risk patients. Late toxicity, including erectile function preservation, appears comparable/superior to conventional radiation therapy. CyberKnife SRS is a noninvasive and convenient treatment option for patients with early stage prostate cancer.