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- 1. - Large patientcohort prospective study with more than 500 patients and more than 5 years follow up have shown that CyberKnife is equally effective as long coures RT - SBRT/ CyberKnife is now standard of care treatment for localized prostate cancer - Outcome of CyberKnife treatment is similar to long course RT - Side-effect after Cyberknife is less than 1% in prostate cancer - CyberKnife is safe, out patient, short course treatment in both primary and metastatic diseases. - High dose radiation may be effective in many of the ‘radioresistant’ disease. CyberKnife in prostate cancer
- 2. • Most prevalentmalignancy in males in western community • 2nd MC cause of mortality in the west • Uncommon in Asians, probably shorter lifespan • In TMH, constitutes 2.4% of all registered pts in 2000 • In recent years, more early prostate cancer patients are diagnosed with prostate cancer • Prostate cancer is slow growing tumour, risk of bone metastasis is high in ‘high risk’ group patient Prostate cancer
- 3. Risk stratification RISK STRATIFICATION LOWRISK INTERMEDIATE HIGH T1,2a, PSA < 10 ng/ml, GS</=6 T2b, GS=7 T3,4,PSA>20ng/ml, GS>7 Wait & watch Surgery Radiation therapy HT Radiosurgery Combination Surgery Radiation therapy HT Radiosurgery Combination Surgery Radiation therapy HT Radiosurgery Combination
- 4. Radiotherapy Radiation techniques: 2D Planning ConformalRadiation therapy - 3D-CRT - IMRT - SBRT Target volume: CTV – prostate with capsule + SV T1 & small T2 with less PSA less GS only prostate is sufficient. PTV – 1 cm margin. Inclusion of pelvic lymph nodes still controversial.
- 5. Ca prostate Incidence ofpelvic LN metastasis at diagnosis Study T1a,b T1c T2a T2b,c T3 Pisansky 12/457 (2.6%) 15/456 (3.3%) 130/1206 (10.8%) 81/320 (25%) - Petros & Catalona 2/61 (3.3%) 33/425 (7.8%) 0 Sands 6/127 (5%) 41/243 (16.9%) 95/199 (47.7%) Van Poppel 2/40(5%) 18/199 (9%) 25/46 (54%) Hanks 1/21(5%) 38/135(28%) 48/95(50%)
- 6. Radiotherapy Radiation therapy schedules Conventionalfractionation: - 70Gy/ 35# / 7 wk - 2Gy/# - Acute rectal & bladder toxicity Hypofractionation schedule: - High dose per fraction, short course treatment - Equivalent loco-regional control Ultra-hypofractionation schedule: - Very short course, high dose per fraction - Usual treatment duration 5 to 7 days
- 7. Conformal Radiation therapy reducestoxicity • RCT • Royal Marsden Tait et al. Gr 2 or more 5 Vs 15%. • Rotterdam trial Koper et al. Grade 2 GI toxicity (32% vs. 19%, p = 0.02). • M.D. Anderson Storey et al. No dif but Dose 78 vs 70. • Nonrandomized trials • 15/27 improvement • Most pronounced when dose escalation was not used. • When dose escalation was used, no increased toxicity was demonstrated, except when the dose to the rectum >75 Gy. • No article suggested increased toxicity with 3D-CRT for similar doses delivered compared with conventional RT.
- 8. WPRT VS PORT:RTOGtrial 9413 • WP RT NCHT improves PFS compared with PO RT and NCHT or PO RT and AHT, and compared with WPRT + AHT in patients with a risk of LN involvement of 15%. •Median follow-up : 59.5 mnths • No OS advantage JCO 2003
- 9. Subset analysis ofRTOG 9413 •Median PFS was 5.2, 3.7, and 2.9 years ( p 0.02). •7-year PFS was 40%, 35%, and 27% •RT field size has a major impact on PFS, and it is advised that nodal treatment should be done in patients with a risk of LN inv >15% . Roach IJROBP 2006
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- 12. Author Study typePatient criteria Study details Results Kurban et al Prospective multi- institutional N= 4839 1986-95 T1-2 low risk prostate cancer No neo-adj HT RT dose 60-78 Gy 3DCRT planming Median FU 6.3 yrs 8-year PSA control rates were 72 to 93%. Dose >72 Gy had lower PSA relapse rate. Zietman MDACC Randomized N= 393 T1-2 disease PSA < 105ng/dl Arm 1: Conv RT 70.2 Gy Arm 2: Conv RT 79.2 Gy Median FU: 5.5 yrs 5-yr PSA rFS higher with dose escalation (61% vs 80%). 49% risk reduction in biochemical failure. Pollack et al MDACC Randomized N=301 Low risk prostate cancer Arm 1 (n=150): Conv RT 70 Gy Arm 2 (151): 3DCRT 78 Gy PSA rFS higher with dose escalation (70% versus 64%; p=0.03) Peeters et al Randomized Netherland N=669 T1-4 Arm 1 (n=150): Conv RT 68 Gy Arm 2 (151): Conv RT 78 Gy Median FU: 51 months 5-yr PSA relapse-free survival superior with high dose (64% vs. 54%; p = .02). Zelefsky et al Randomized MSKCC N=1100 1988-98 RT dose systematically increased from 64.8 to 86.4 Gy by increments of 5.4 Gy in consecutive groups of pts. 5-yr PSA rFS was higher with dose escalation in favorable, intermediate and unfavourable groups. Zelefsky et al Single arm N=561 1996-2000 RT dose: 81 Gy to PTV 8-yr PSA rFS for favorable-, intermediate-, and unfavorable- risk groups were 85%, 76%, 72% Prostate Cancer: Dose escalation studies
- 13. Intensity modulated radiationtherapy 76- 81 Gy at 2 Gy/# dose delivered Dose to target higher Rectal & Bladder dose is high High acute reactions Dose escalation methods IMRT/ 3DCRT
- 14. Toxicities after Radiationtherapy Rectal toxicity - Telengectasia - Bleeding - Bladder toxicity - Incontinence - Bleeding - Thimble bladder - Urethral stricture -Erectile dysfunction - Quality of life
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- 16. Author Study Patientcriteria Study details Results Martin Prospect ive PMH N= 92 June 2001- Mar 2004 60 Gy /20 fr/ 4 wks IMRT, FU: 38 mo 3 yr PSA relapse free was 76%. RTOG Gr ≥3 GI toxicity in 1 patient Kupelian Clevelan d Clinic N= 770 1998-2005 70 Gy; 2.5-Gy/fr/ 5 wks. FU: 45 mo 5 yr PSA relapse free of low, intermediate and high-risk disease was 95%, 85%, and 68%, respectively. Livsey Retrospe ctive Manches ter N= 705 men T1-T4 disease 1995 -1998 Conformal RT (50 Gy/16fr/ 22 days) Median FU: 48 months Favourable, intermediate, poor prognostic groups biochemical control was 82%, 56%, and 39%. RTOG Gr ≥2 GI and bowel toxicity was 5% and 9%. Lukka Randomi zed NCI Canada N= 936 Mar 1995- Dec1998 Long arm: 66 Gy/33 fr 45 days Short arm: 52.5 Gy/20 fr 28 days 5 yrs, PSA relapse free survival was 52.95% in long and 59.95% in short arm. GI toxicity higher with short arm (11% vs 7%) Tsuji Chiba Japan N=201 June 1995-Feb 2004 Three clinical trials RTOG Gr ≥2 GI toxicity. 5-yr PSA relapse-free survival 83.2% without any local recurrence. Prostate Cancer: Hypofractionation studies
- 17. Author Study Patientcriteria Study details Results King Prospective N=41 Stanford SBRT (CyberKnife) 36.25 Gy/ 5 fr/ 1 week Median FU: 33 months Biochemical control 100% At 12 months, 78% achieved PSA nadir RTOG Gr ≥3 rectal toxicity 4.8% Friedland Prospective N=112 Naples Feb2005-Dec 2006 SBRT (CyberKnife) RT dose: 35-36 Gy/5 fr Median FU: 24 months 3 patients had failure (two local and one distant failure). 82% no erectile dysfunction Brachytherapy Galalae Three centre data N=611 Localized prostate cancer HDR brachytherapy combined with EBRT 5-yr PSA relapse-free survival were 96%, 88%, and 69% for favorable-, intermediate-, and unfavorable-risk patients Prostate Cancer: Ultra-hypofractionation studies
- 18. Fullar et al,IJROBP 2008 Radiosurgery mimicking brachytherapy
- 19. Fullar et al,IJROBP 2008 Radiosurgery mimicking brachytherapy
- 20. Fullar et al,IJROBP 2008 Radiosurgery vs brachytherapy: Dosimetry
- 21. Radiosurgery vs brachytherapy:Dosimetry Fullar et al, IJROBP 2008
- 22. Hossain et al,IJROBP 2010 SBRT vs IMRT : Dosimetry
- 23. Hossain et al,IJROBP 2010 SBRT vs IMRT : Dose distribution
- 24. Hossain et al,IJROBP 2010
- 25. Hossain et al,IJROBP 2010
- 26. Hossain et al,IJROBP 2010
- 27. SBRT: Early outcomeof Ph II study (n=45)
- 28. SBRT: Early outcomeof Ph II study (n=45)
- 29. SBRT: Clinical outcome(n=112) Frieland et al, IJROBP 2009
- 30. Probability of maintainingerectile function Robinson et al IJROBP 2002
- 31. King et al.IJROBP 2010 QOL: Sexual function domains 5 yr FU data with biochemical control & QOL function
- 32. QOL: Sexual functiondomains King et al. IJROBP 2010
- 33. Aluwin J ofEndourology 2010 Experiences from new centres
- 34. Conclusions - Large patientcohort prospective study with more than 500 patients and more than 5 years follow up have shown that CyberKnife is equally effective as long coures RT - SBRT/ CyberKnife is now standard of care treatment for localized prostate cancer - Outcome of CyberKnife treatment is similar to long course RT - Side-effect after Cyberknife is less than 1% in prostate cancer - CyberKnife is safe, out patient, short course treatment in both primary and metastatic diseases. - High dose radiation may be effective in many of the ‘radioresistant’ disease.
- 35. Thank you Dr DebnarayanDutta, MD CyberKnife Specialist duttadeb07@gmail.com