How to interpret PSA changes after focal therapy?

Transcription

1 How to interpret PSA changes after focal therapy? Roman Ganzer, MD Klinik und Poliklinik für Urologie Universität Regensburg Caritas-Krankenhaus St. Josef Direktor: Prof. Dr. W.F. Wieland

2 Focal therapy a hot topic! Radical prostatectomy Overtreatment? Side effects? Active Surveillance Tumor progression Safety? Anxiety?

3 Focal therapy a hot topic! Focal Therapy Radical prostatectomy Overtreatment? Side effects? Active Surveillance Tumor progression Safety? Anxiety?

4 Focal therapy a hot topic! Patient selection Biopsy Imaging Technoloy

5 Focal therapy a hot topic! Patient selection Biopsy Imaging Technoloy New paradigm in prostate cancer treatment

6 What studies show Feasibility With different technologies

7 What studies show Feasibility With different technologies Favorable functional outcome Preservation of genitourinary function in 80-90%

8 What studies show Feasibility With different technologies Favorable functional outcome Preservation of genitourinary function in 80-90% Early oncologic results Biopsy results after 6 to 12 months

9 Focal studies oncologic endpoints Biopsy results Imaging Impact of additional therapy

10 ... But what about?

11 PSA after focal therapy why difficult? No accepted definition of biochemical failure following focal therapy of prostate cancer!

12 PSA after focal therapy why difficult? No accepted definition of biochemical failure following focal therapy of prostate cancer! Variety of different definitions is used

13 PSA after focal therapy why difficult? No accepted definition of biochemical failure following focal therapy of prostate cancer! Variety of different definitions is used Biology of prostate cancer Long natural history High number needed to treat to save one life

14 PSA after focal therapy some difficulties...

15 PSA after focal therapy some difficulties... What is focal therapy? Different types of definitions

16 PSA after focal therapy some difficulties... What is focal therapy? Different types of definitions Hemiablation

17 PSA after focal therapy some difficulties... What is focal therapy? Different types of definitions Hemiablation ¾-Ablation

18 PSA after focal therapy some difficulties... What is focal therapy? Different types of definitions Hemiablation ¾-Ablation Index-Tu Ablation

19 PSA after focal therapy some difficulties... What is focal therapy? Different types of definitions Hemiablation ¾-Ablation Index-Tu Ablation Focal Ablation

20 PSA in a partially ablated prostate...

21 PSA in a partially ablated prostate Ablated tissue

22 PSA in a partially ablated prostate Ablated tissue 2. Healthy tissue

23 PSA in a partially ablated prostate Ablated tissue 2. Healthy tissue 3. Untreated insignificant cancer

24 Different treatment modalities influence on PSA? Cryotherapy HIFU Interstitial Lasertherapy

25 Different treatment modalities influence on PSA? Cryotherapy HIFU Interstitial Lasertherapy Ablative-specific treatment response of PSA?

26 PSA in a partially ablated prostate...

27 PSA in a partially ablated prostate... Unlikely to be zero

28 PSA in a partially ablated prostate... Unlikely to be zero Criteria for active surveillance might not be suitable

29 PSA in a partially ablated prostate... Unlikely to be zero Criteria for active surveillance might not be suitable Criteria for RTX failure might not be suitable (ASTRO, Phoenix)

30 ... Knowledge on PSA after focal therapy... PSA is the less understood parameter in focal prostate cancer treatment

31 Biochemical failure criteria in standard procedures RPE + RTX Variety of biochemical failure definitions: 53 definitions for radical prostatectomy 99 definitions for radiation therapy (review of literature ) Cookson et al. J Urol 2007

32 Biochemical failure criteria in whole gland ablation no consensus exists!

33 Biochemical failure criteria in whole gland ablation no consensus exists!

34 Biochemical failure criteria in whole gland ablation no consensus exists!

35 Biochemical failure criteria in whole gland ablation no consensus exists!

36 Short follow-up of focal studies 3.6 years 15.2 ± 7.4 mo 28 mo 70 mo 34 mo

37 Short follow-up of focal studies 3.6 years 15.2 ± 7.4 mo 28 mo 70 mo 34 mo Few studies with too short follow up No 10-year follow-up data PC specific death + time to metastasis: much longer follow-up needed

38 Focal therapy more reviews than originals Lindner et al. Nature 2010

39 Focal therapy more reviews than originals Lindner et al. Nature 2010

40 What parameter can be used? PSA cut off? ASTRO? Phoenix? PSA doubling time? PSA velocity? PSA nadir??

41 Focal studies which PSA criteria are used? 77 patients, unilateral prostate cancer Hemi Cyroablation Follow-up Serial PSA TRUS guided biopsy (in 22 patients with suspicion of recurrence) Truesdale et al. Cancer 2010

42 Focal studies which PSA criteria are used? 77 patients, unilateral prostate cancer Hemi Cyroablation Follow-up Serial PSA TRUS guided biopsy (in 22 patients with suspicion of recurrence) Definition of biochemical failure: Phoenix criteria (PSA nadir + 2ng/ml) Truesdale et al. Cancer 2010

43 Focal studies which PSA criteria are used? Results: Median follow-up: 24 (0-87 months) 10/22 (45.5%) had positive biopsies Truesdale et al. Cancer 2010

44 Focal studies use of Phoenix criteria? Truesdale et al. Cancer 2010

45 Focal studies use of Phoenix criteria? 75% failure at 3 years Truesdale et al. Cancer 2010

46 Focal studies use of Phoenix criteria? 75% failure at 3 years 35% failure at 3 years Truesdale et al. Cancer 2010

47 Focal studies use of Phoenix criteria? 75% failure at 3 years 35% failure at 3 years High biochemical failure rates Poor correlation with pathological results Truesdale et al. Cancer 2010

48 Focal studies use of Phoenix criteria? 75% failure at 3 years 35% failure at 3 years High biochemical failure rates Poor correlation with pathological results Conclusion: Phoenix criteria might not be accurate to define cancer progression Truesdale et al. Cancer 2010

49 Focal studies without PSA failure criteria 20 patients, unilateral cancer following HIFU hemiablation Follow-up: PSA at 1, 3, 6, 9, 12 months MRI at months Perineal template biopsy at 6 months Ahmed et al. J Urol 2011

50 Focal studies without PSA failure criteria Results: Trifecta in 89% of patients at 12 months Ahmed et al. J Urol 2011

51 Focal studies without PSA failure criteria Results: Trifecta in 89% of patients at 12 months Ahmed et al. J Urol 2011

52 Proposed + ongoing multicentre phase II trials

53 Proposed + ongoing multicentre phase II trials

54 Ahmed et al. WJU 2010 Suitable outcome measures

55 Focal studies Biochemical versus biopsy results PSA Biopsy

56 Conclusion 1 No consensus on biochemical failure following focal prostate cancer treatment

57 Conclusion 1 No consensus on biochemical failure following focal prostate cancer treatment Failure criteria for other treatments are not suitable Radical prostatectomy Radiation therapy Full gland ablation Active surveillance

58 Conclusion 2 Follow-up biopsy 12 month treated area Imaging Multiparametric MRI Time of secundary treatment

59 Conclusion 2 Follow-up biopsy 12 month treated area Imaging Multiparametric MRI Time of secundary treatment +PSA every three months Sensitivity analyses of different PSA scenarios to find an adequate definition of PSA failure following focal therapy of prostate cancer

60 Thank you very much