Radiation Therapy for Prostate Cancer. Resident Dept of Urology General Surgery Grand Round November 24, 2008

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1 Radiation Therapy for Prostate Cancer Amy Hou,, MD Resident Dept of Urology General Surgery Grand Round November 24, 2008

2 External Beam Radiation

3 Advances Improving Therapy Generation of linear accelerators and conformational techniques allowing delivery of high doses of radiation deep into pelvis while respecting normal tissue surrounding target Image guided techniques allowing for placement of radioactive sources directly into prostate, versus free-hand

4 Technique CT scan of pelvis in treatment position Planning target volume (PTV) Prostate +/- seminal vesicle Margin of 0 to 4-6mm 4 or more around the prostate Smaller margin on rectal side, due to fear of rectal toxicity Definition of rectal length/ volume varies

5 Conventional radiation therapy treatment portal (A). Prostate location inferred from the foley balloon, bladder and wire anal marker. Conformal radiation therapy treatment portal (B). 3D prostate reconstructed from planning CT scan.

6 IMRT Conformal dosing to the prostate During each beam angle, a part of the radiation field is blocked at a specified time to optimize treatment to prostate but limit dose to surrounding structures At any given time, multiple beams consecutively fired and converging on target organ

7

8 PSA Bounce 964 men treated with full dose EBRT alone for localized prostate cancer at MD Anderson PSA bounce defined as initial increase in serum [PSA] >= 0.5ng/ml, with return to pre-bounce baseline serum PSA no more than 60mo after EBRT

9 PSA Bounce - Results 12% (119 pts) with PSA bounce, mean time 18months after treatment No pretreatment factors or radiation dose could predict PSA bounce Had significantly higher biochemical disease- free survival than those without bounce (p=0.0001) 34.3% (334pts) with biochemical recurrence at median of 21 months after treatment

10 Time to PSA Bounce Rosser CJ, Kuban DA, et al. The PSA bounce phenomenon after EBR for clinically localized CaP. J Uro 2002; 168:

11 Dutch Multicenter Dose Escalation Trial Randomized, multicenter trial looking at dose escalation of EBRT for localized prostate cancer 669 patients between Median 70month followup in 68Gy vs 78Gy radiotherapy Neo/adjuvant hormone therapy allowed Balanced between both treatment arms

12 78Gy vs 68Gy Primary endpoint: Freedom from failure, clinical and biochemical ASTRO BF definition 3 consecutive rises in PSA Phoenix BF definition nadir PSA + 2mg/L Better 7year freedom from failure rates with 78 Gy by both definitions ASTRO: 54% vs 47%, p = 0.04 Phoenix: 56% vs 45%, p = 0.03 No statistically significant difference in FFCF and overall survival

13 Complications -78 Gy vs 68 Gy Grade 2 or greater GU toxicity Incidence similar in the two arms 40% vs 41%, p = 0.06 Gardner et al demonstrated a 59% GU toxicity rate in a 15year followup Grade 2 or greater GI toxicity Cumulative incidence greater in 78 Gy arm 35% vs 35%, p = 0.04 Rectal bleeding and fecal incontinence 2x more common

14 Al-Mamgani A, et al. Update of Dutch multicenter dose-escalation trial of radiotherapy for localized CaP. Int J Rad Onc Biol Phys 2008; 72(4):

15 Complications of Radiation Therapy GU (56% (MGH)) Urethral stricture Total incontinence Bladder cancer (5.6%)* Continues over time 13% of patients with acute urinary toxicity eventually developed chronic urinary toxicity vs 5% who did not GI Proctitis Fecal incontinence GI bleed Secondary GI cancer

16 Nieder AN, et al. Radiation therapy increases risk of bladder and rectal cancer. J Uro 2008; 180:

17

18 Brachytherapy Insertion of radioactive implants Via TRUS (Holm 1983), CT (Koutrevelis( 1998) or MRI (D Amico 1998) Under US visualization, 17 or 18-gauge needles inserted through template into prostate Metallic seeds containing radioactive isotope deployed as needles withdrawn Walsh, Retic,Vaughan, Wein, eds. Campbell s Urology, 8 th ed. 2002

19 Prostatic Template: Transperineal As described by Puthawala: 2 concentric rings with radii of 1-2cm guide holes Up to 18 metallic source guides, 17gauge, 20cm long Tips of guides usually 1cm above bladder neck Template fixed to perineum by silk suture Gunderson LL, Tepper JE, eds. Clinical Radiation Oncology, 2 nd ed. Elsevier 2007.

20 Prostatic Implants Permanent Iodine 125 Palladium 103 implants Shorter t1/2 vs I days vs 60days Lower energy 21KeV vs 27KeV Means slightly lower tissue penetrance,, made insignificant if seed to seed distances are 1.7cm or less

21 Patient placed in high lithotomy position with transrectal ultrasound probe fixed to the stepper device. Needle containing radioactive seeds inserted transperineally via a grid. Walsh et al. Campbell s Urology, 9 th ed.

22 Tranverse US image. Several seeds visible in anterior gland. Arrow pointing to target location for seed placement.

23 Parasagittal US image. Arrow demonstrates needle depth goes to the prostatic capsule before deploying radioactive seeds.

24 Intraoperative fluoroscopic image of the prostate demonstrating placement of palladium 103 seeds.

25 Toxicitities Urinary 37% with grade I toxicity in 1 st 60 days 68% resolution of grade II toxicity at 36mo 1-5% require CIC 2-3% overall significant urinary obstruction (refractory to medical mgmt) s/p brachytherapy Rectal 1-4% minor rectal bleeding Rate of toxicity related to dose and length of rectal wall receiving dose Wallner (1995): keep rectal dose to 85% of prescribed dose

26 Potency Zelefsky reported improved rates of potency over EBRT * 53% vs 43% (p= 0.52) Rate of potency decreases with longer followup 50% of potent men pre-treatment will be potent 6 years post-treatment treatment Zelefsky MJ, et al. Comparison of 5yr outcome and morbidity of 3DCR vs transperineal permanent I-125. J Clin Oncol 1999; 17:

27 Stock RG, Stone NN, Ianuzzi C. Sexual potency following interactive US-guided brachytherapy for CaP. Int J Radiat Oncol Biol Phys 1996; 35:

28 Comparison of treatments Cleveland Clinic, Kaiser Permanente Looked at 5 year biochemical relapse free survival T2b, T2c, gleason 7- intermediate risk CaP Open prostatectomy, laparoscopic prostatectomy, EBRT, or brachytherapy 79.9% vs 60.2% vs 85.7 % vs 89.5% (p<0.0001) Vassil AD, et al. A comparison of BRFS and initiation of salvage therapy in patients with intermediate risk CaP treated with open RP, lap RP, EBRT or PSI. IJ Rad Onc Biol Phys 2008; 72(1): s286.

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