SRO Tutorial: Prostate Cancer Clinics

Transcription

1 SRO Tutorial: Prostate Cancer Clinics May 7th, 2010 Daniel M. Aebersold Klinik und Poliklinik für Radio-Onkologie Universität Bern, Inselspital

2 Is cure necessary in those in whom it may be possible, and is cure possible in those in whom it is necessary? W.F. Whitmore Jr. Urol Clin North Am 1990; 17: 689

3 Improvement of utcome of locally advanced prostate cancer... by improvement of loco- (regional) tumor control systemic tumor control Androgen deprivation Dose escalation

4 Androgen deprivation

5 EBRT (70 Gy) + 3 year LHRH treatment EORTC Biochemical control Biochemical relapse-free survival p < hazard ratio years [M. Bolla et al., Lancet 360: ,2002] 70 Gy + LHRH 70 Gy

6 100 EBRT (70 Gy) + 3 year LHRH treatment EORTC Overall survival Overall survival (%) Gy + LHRH 70 Gy 20 Log-rank p < [M. Bolla et al., Lancet 360: ,2002] hazard ratio Number of patients at risk: Time since randomisation (years)

7 Major Studies of Antiandrogenic Hormonal Treatment Combined with RT (I) Study Treatment Locoreg. Control Distant metastasis NED-S OAS EORTC T3, 4 or N1, 2 or G3, 5 year actuarial rate RT vs. RT + goserelin starting with RT for 3 years whole pelvis 73 vs. 98 % 29 vs. 10 % 45 vs. 76 % (bned) 62 vs. 78 % p = RTOG year actuarial rate RT vs. RT + goserelin from last week of RT for life or until progression whole pelvis 62 vs. 77 % 39 vs. 24 % 9 vs. 31 % (bned) 39 vs. 49 % p < Prospective subgroups Gleason score 2-6 Gleason score 7 Gleaseon score vs. 57 % ns 42 vs. 52 % p: vs. 39 % p:

8 Major Studies of Antiandrogenic Hormonal Treatment Combined with RT (II) Study Treatment Locoreg. Control Distant metastasis NED-S OAS RTOG 8610 T2-4: palpable tumor 25 cm 2 or N1,2 centrally reviewed Gleason score 2-6 (NED-S; 5 years) RT or RT + CAB T2-4: palpable before and during RT whole pelvis 58 vs. 70 % p = actuarial 8 years 45 vs, 34 % p= vs. 16 % p = 0.001) 13 vs. 45 % p = (bned) 44 vs. 53 % p = vs. 70 % p = RTOG 9202 T2c-4 Subgroup (retrospective) with Gleason score 8-10 Long vs. Short hormonal treatment: CAB 2 months before and during RT vs. same + 2 years goserelin whole pelvis 87 vs. 94 % p = year actuarial rate 90.9 vs % p = vs % p = vs % p = vs % p = vs. 35 % p = vs. 54 % (ns) 78.5 vs. 80 % (ns)

9 Major Studies of Antiandrogenic Hormonal Treatment Combined with RT (III) Study Treatment Results RTOG 9413 T1c-T4, PSA < 100 Estimated risk of LN Involvement >15 % Whole pelvis (wp) or local RT and hormonal treatment 2 months before (N) and during (CHT) RT or after RT for 4 months After 4 years whole pelvis: better NED vs. local RT wp + N +CHT better NED vs. other 3 arms Overall survival: longer follow-up needed MetaAnalysis RTOG BJC 90, 2004, 950 Bulky T1,2 + Gleason Score 2-6 or T1,2 Gleason Score 7: benefit of short HAT (before and during RT) vs. HAT (benefit of longer HT)?) T3 Gleason Score 7 or Gleason Score 8-10: benefit of long term HAT vs. Short term HAT (2 or 3 or 5 years or longer?)

10 EBRT plus Androgen Deprivation Short term vs long term? Indication dependent on Grading, T stage and PSA? Still needed when total RT dose increased?

11 Dose escalation

12 Dosis-Eskalation Retrospective Data... Kupelian 2002: Cleveland Hanks 2002: Fox Chase CC Leibel 2003: Memorial Sloan Kettering CC...

13 Memorial SK CC: Low Risk % PSA Relapse-Free Survival > 80 Gy 75.5 Gy < 72 Gy (n = 285) (n = 91) (n = 115) Months p = 0.01 p = [Leibel (2003); Sem Oncol 30:596]

14 Memorial SK CC: Intermediate Risk % PSA Relapse-Free Survival > 80 Gy 75.5 Gy < 72 Gy (n = 346) (n = 144) (n = 158) Months p < p = [Leibel (2003); Sem Oncol 30:596]

15 Memorial SK CC: High Risk % PSA Relapse-Free Survival > 80 Gy 75.5 Gy < 72 Gy (n = 207) (n = 135) (n = 203) Months p < p = [Leibel (2003); Sem Oncol 30:596]

16 Optimal dose? Randomised trials > 74 Gy Trial Dose Technique End point Percent p MDACC 70 vs 78 3DCRT FFF 5 yrs 48 vs MGH/ Loma Linda 70.2 vs DCRT + Protons FFP 5 yrs 66 vs 86 <0.01 NCI/ Amsterdam 68 vs 78 3DCRT ongoing RTOG vs DCRT ongoing

17 MDACC Trial 2000 All patients; n = 305, T1-3 Nx 78 Gy 70 Gy [Pollack ( 2000); J Clin Oncol 18:3904]

18 MDACC Trial 2000 PSA 10 ng/ml; n = Gy 70 Gy [Pollack ( 2000); J Clin Oncol 18:3904]

19 MDACC Trial 2000 PSA > 10 ng/ml; n = Gy 70 Gy [Pollack ( 2000); J Clin Oncol 18:3904]

20 Radiation therapy with 70/78 Gy (random) Factor Pre-Tx PSA % 5- Year FFF* 70 Gy 78 Gy No. of Patients No. at Risk % 5- Year FFF* No. of Patients No. at Risk P < 10 ng/ml > 10 ng/ml Stage T1/T T GS * FFF = Fredom from clinical / biochemical failure A. Pollack et al., J Clin Oncol 18: , 2000

21 MDACC Trial 2000 Grade 2 or higher complications [ Storey( 2000); IJROBP 48:635]

22 MGH/Loma Linda: 70.2 GyE vs 79.2 GyE Zietman JAMA 2005

23 HDR-BT plus EBRT: Results Biochemical control: 75-90% [Vicini et al. (2003); Sem Radiat Oncol 13:98]

24 Fraction Controlled EBRT plus HDR-BT WBH, Kiel, Seattle: n = 611 p < Times in Years [Galalae 2004; IJROBP 58:1048] Favorable (46) Intermediate (188) High (359)

25 HDR-BT plus EBRT: Late toxicity 10-20% Grad 2 5% Grad 3 <10% Grad 2 3% Grad % [Vicini et al. (2003); Sem Radiat Oncol 13:98]

26 HDR-BT plus EBRT: Late toxicity Institution William Beaumont Hospital [Martinez; IJROBP 2002] Toxicity GU [RTOG Grade 3] Strictures: 2.4 % Toxicity GI [RTOG Grade 3] Bleeding: 0.5% Seattle Prostate Institute Strictures: 7% Bleeding: 0% [Mate; IJROBP 1998]

27 Comparison: HDR-BT plus EBRT vs high dose EBRT Biochemical control at 5 years Author Low Intermed High Zelefsky 1998 Leibel 2003 Galalae % 96 % 96 % 65 % 87 % 87 % 35 % 69 % 69 %

28 Dose escalation: open questions Impact of hormon therapy? Optimal dose? Impact of locoregional control?

29 Wertigkeit der Androgen-Deprivation? 1.0 Fraction Controlled C-HDR (N=330) Androgen suppression + C-HDR (N=177) p= Time in Years [Martinez et al. (2003); IJROBP 179:2296]

30 Impact of androgen deprivation for HDR-BT plus EBRT: Pooled data (I) Intermediate Risk Endpoint (5 years) No ADT (n = 137) ADT (n = 51) p values OS CSS BC DFS 86 % 100 % 87 % 73 % 90 % 97 % 91 % 85 % [Galalae 2004; IJROBP 58:1048]

31 Impact of androgen deprivation for HDR-BT plus EBRT: Pooled data (I) High Risk Endpoint (5 years) No ADT (n = 240) ADT (n = 119) p values OS CSS BC DFS 87 % 97 % 69 % 60 % 80 % 90 % 68 % 61 % [Galalae 2004; IJROBP 58:1048]

32 Pelvic irradiation

33 Bedeutung der loko-regionären Kontrolle? RTOG 9413 Stratum PFS (4 yrs) Prostate + AHT 50% Prostate+ NCHT 44% Prostate + LN + AHT 49% Prostate + LN + NCHT 60% p = [Roach 2003; J Clin Oncol 21:1904]

34 GETUG-01 Pelvic RT: no benefit

35 Pelvic RT: No relevant increase of tox

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37 Uncovered issues Adjuvant vs. salvage RT after radical prostatectomy Hypofractionation Noval concepts (e.g. dose painting) Treatment of systemic relapse