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Latest developments in Prostate Cancer

7th ESMO Patient Seminar Stockholm 14 / 09 / 2008. Latest developments in Prostate Cancer. Hein Van Poppel Chair Sc.Comm. Leuven, Belgium . Relative Survival* (%) during. Source: SEER Program, 1975-2000, NCI, 2003. 1974-1976. 1983-1985.

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Latest developments in Prostate Cancer

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  1. 7th ESMO Patient Seminar Stockholm 14 / 09 / 2008 Latest developments in Prostate Cancer Hein Van Poppel Chair Sc.Comm. Leuven, Belgium

  2. Relative Survival* (%) during Source: SEER Program, 1975-2000, NCI, 2003. 1974-1976 1983-1985 1992-1999 Site • Breast (female) 75 78 87 • Colon & rectum 50 57 62 • Leukemia 34 41 46 • Lung & bronchus 12 14 15 • Melanoma 80 85 90 • Non-Hodgkin lymphoma 47 54 56 • Ovary 37 41 53 • Pancreas 3 3 4 • Prostate 67 75 98 • Urinary bladder 73 78 82

  3. 1. SCREENING andEARLY DETECTION

  4. Anything next to PSA? • PCA3 • EPCA

  5. A New Test on the Horizon • PCA3DD3 is the most prostate-cancer-specificgene described to date • Over-expressed in >95% of PC • Expression restricted to the prostate

  6. But…How reliable is the 35 cut-off ?

  7. The EPCA Test

  8. EPCA : “A PrCa revolution” • Early Prostate Cancer Antigen - 2 Dr.Getzenberg et al., J.Urol.2007 • Structural protein in the nucleus of Pr Ca cells Function? • False Positive : 3%...had no cancer • False Negative : 6%...had cancer • Separates Prostatitis , BPH • Identifies -more or less aggressive cancers -localized and locallly advanced Ca

  9. PSA remains keyPCA3 and other markers help in counseling, deciding …on biopsy, repeat biopsy, and also on management

  10. Urine Biomarkers • Expression of Prostate specific genes - TMPRSS2 : ERG fusion status - GOLPH2, SPINK1, PCA3 expression = all significant predictors of PrCa • Combination PCA3 + TMPRSS2 –ERG expression in urine is better than PSA and PCA3 Chinnaiyan, Cancer Res. 2008

  11. Other genetic markers • In PrCa gene fusions involving oncogenic ETS transcription factors like ERG, ETV1 and ETV4 have been identified • Most common fusion: TMPRSS2 fused to ERG • Fusion to ETV1: TMPRSS2, SLC45A3, HERV-K_22911.23, C150RF21, HNRPA2B1 • ETV5 (new oncogene ETS transciption factor): TMPRSS2, SLC45A3 Helgeson, Cancer Res. 2008

  12. Other genetic markers • Gene MSMB and LMTK2 in blood  genetic profiling can be offered to men to assess the risk of developing PrCa Ros Eeles, Nature Genetics 2008

  13. 2. PREVENTION

  14. Widespread use of finasteride: cost-effective? • Finasteride is unlikely to be cost-effective when considering the impact on survival differences • Maybe cost-effective in high-risk population Svatek et al., Cancer 2008

  15. Recent Literature on Chemoprevention

  16. Chemoprevention I.Thompson,JUrol ‘07 • PCPT : - finasteride reduces PrCa prevalence - decreases PIN • PLCO :- vegetable intake decreases ECE - spinach,brocoli,cauliflower • Physician’s Health Study: -Vit.D - marine source fatty acids • Soy, Vit E and Se suppl. decreases HGPIN V.Kirsh,JNCI ‘07 H.Li et al., NCPU ‘07 Chavarro, CEBP ‘07 S.Joniau, Urology ‘07

  17. Cholesterol lowering drugs decrease the risk of PrCa in a dose dependent matter Atorvastatin, Lovastatin, Simvastatin Murtola, UroToday, 2008 Genistein decreased metastasis from PrCa by 96 % in mice without effect on the primary R. C. Bergen, Cancer Res. 2008

  18. 3. BONE STAGING

  19. Place of MRI in Bone Staging • Bone scan still standard diagnostic tool - if normal = OK, no MRI - if abnormal - X-ray normal  MRI - X-ray explains bone scan  no MRI Venkitaraman, JCO 2007

  20. 4. MANAGEMENT

  21. 1. Radical Prostatectomy • 2. Active Surveillance • 3. Radiotherapy –Brachy • 4. HIFU and Cryo • 5. Focal therapies • 6. Medical treatments

  22. Primary Treatment according to Specialist Consult (N-85.088) T. Jang, NCI, 2007

  23. Primary Treatment according to Specialist Consult (N-85.088) T. Jang, NCI, 2007

  24. 1. RADICAL PROSTATECTOMY

  25. SURGICAL QUALITY of RPr • Not only laparoscopic radical prostatectomy but also open surgery is not always well performed • Experts in both techniques will have better results, novices and ill trained or unskilled surgeons will perform poorly with both approaches

  26. Radical Prostatectomy (RPr) • Nerve sparing RPr improves continence rates Nandipati et al., Urology 2007 • Laparoscopic RPr can give rise to port site metastasis Savage et al., Urology 2007 • Robot versus open: health related outcomes are equal - 117 Robot vs. 89 open RPr, self-administered questionnaire - Robot less narcotics (32 mg versus 52 mg) shorter hospitalisation (1,2 versus 1,3 days) equal time back to normal activity D.P. Wood et al., Urology 2007

  27. What about the Robot? • Pain • Recovery • Early Continence • Early Potency

  28. RPr in very high risk disease Experience with RRP for PSA >100 26 pts, with median fu of 66.5 months (range 12-158) J oniau, Gontero and Van Poppel, data on file

  29. Multimodal treatment of life-threatening cancers Radical Prostatectomy followed by adjuvant / salvage radiation or hormone treatment

  30. 2. SURVEILLANCEACTIVE MONITORING- WATCHFUL WAITING

  31. PRIAS trial : Inclusion • PSA below 10 ng/ml • PSA density below 0.2 • Gleason score 6 or less • Sufficient number of biopsies • No more than 2 cores invaded • Clinical T1-T2 • Fit for curative treatment but willing to attend follow-up

  32. PRIAS trial : Follow-up • PSA check / 3mos for 2 years, if stable / 6mos • DRE every 6 months • PSA kinetics (velocity and doubling time) • Repeat PPB at 1, 4, 7, and 10 years

  33. ACTIVE SURVEILLANCE ? • Treatment decisions are influenced by anxiety, more than on disease progression • Delay of treatment can prevent some pts with favorable PrCa from getting effective, low-morbidity treatment • Repeat Biopsy = integral part since 20-30% will have grade progression • After a mean follow-up of 4y, 1/3 pts was treated (Sweden) Latini, JUrol,’07 Loeb, NCPU,’07 Venkitaraman,JUrol,’07 Stattin, NCPU,’07

  34. 3. RADIOTHERAPY

  35. RADIOTHERAPY • External Beam : EBRT • -Modern techniques • -Dose escalation • -Comparison Rad.Prost. • 2. Brachytherapy

  36. 1990 • Surgery: 65% • External: 30% • Brachy.: 5% 2005 •Surgery: 33% • External: 31% • Brachy.: 36% Treatment Trends in the US

  37. RT Dose escalation trials

  38. Dutch Multicentre trial: late side effects • RTOG Grade ≥ 2 • GI 27% vs 32% (p=0.2) • GU 39% vs 41% (p=0.6) BUT • Rectal bleeding 4% vs 9% (p=0.02) • Incontinence pads 7% vs 12% (p=0.03) N.S. ?

  39. Can one compare RPr versus RT?

  40. 15y OS RPr vs RT vs WW RPr RT Obs. Connecticut Tumor Registry 1618 pts, 1990-1992 P.Albertsen et al.,J.Urol. 2007

  41. 1990 • Surgery: 65% • External: 30% • Brachy.: 5% 2005 • Surgery: 33% • External: 31% • Brachy.: 36% Treatment Trends in the US

  42. BrachytherapyBiochemical Control - 10 Years • 125 patients diagnosed 1988 - 1990 • Stage T1 - T2b, Gleason < 6 • Biochemical control -10 years : 85,1 % (ASTRO criteria) • Control based on PSA at diagnosis: • PSA initial 0-4 4-10 10-20 >20 • n 54 42 19 9 • bNED 96 % 76 % 58 % 46% Grimm, IJROBP, 51 : 31, 2001

  43. Clinical Results (bNED) RPr ERT Brachy Seattle Low risk 93% 85% 85% 94% Intermediate risk 66% 64% 35% 74% High risk 40% 38% 10% 50% D’Amico et al, JAMA, 1998

  44. Brachytherapy : Update Literature • 308 Brachy vs 127 RPr multicenter France • Whereas RPr gives a very marked impairment in Health related QoL immediately after treatment with subsequent improvement, brachytherapy shows a moderate but persistent impairment in QoL over 2 years Buron et al., IJROBP, 2007

  45. Place of Brachytherapy in 2007 • Excellent results in well selected patients • Excellent results in centers of excellence • Best results in those that do not need any treatment • Value as alternative to RPr in younger patients ?

  46. 4. HIFU - Cryo

  47. Localized Prostate Cancer- HIFU Treatment- Salvage therapy for local relapse after EBRT failure A last opportunity??

  48. CRYOTHERAPY • LUTS settle down with time ….. • Long-term PSA results awaited ….. • Ongoing E.D. still a problem (?)

  49. CRYOSURGERY: Salvage Treatment Biochemical NED: 40 - 70% after 12 - 50 months COMPLICATIONS Incontinence: 10-80 Impotence: 72-100% Retention/Stricture: 10-55% Pelvic pain: 6-77% Recto-urethral fistula: 0-11% N.Touma. J.Urol. 2005; 173:373-379

  50. Summary • Brachytherapy – low risk patients • HIFU – Salvage therapy • Cryotherapy – Experimental !

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