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Prostate Cancer

Prostate Cancer. Dr. Eliahu Gez Oncology Department Rambam Medical Center Haifa, 2003. Incidence. Most commonly diagnosed malignancy in men At age 50, a man has: 1) 42% chance of developing PC and 2) 3% chance of dying of PC Over 60 years of age

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Prostate Cancer

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  1. Prostate Cancer Dr. Eliahu Gez Oncology Department Rambam Medical Center Haifa, 2003

  2. Incidence • Most commonly diagnosed malignancy in men • At age 50, a man has: 1) 42% chance of developing PC and 2) 3% chance of dying of PC • Over 60 years of age 70% of men have microscopic evidence of PC • The incidence of PC as well as the number of PC deaths are expected to increase

  3. Geographic Variations in PC Incidence and Mortality Rates • Incidence and mortality rates vary dramatically. • Japan, Hong Kong, and Singapore have the lowest mortality rates • Nordic countries and North America have the highest

  4. Age-adjusted mortality rates by country between 1992 and 1995 Norway Switzerland Portugal Sweden Denmark New Zealand Australia The Netherlands Ireland Finland USA Austria UK Germany Canada France Spain Israel Italy Mexico Greece Russian Federation Japan Mortality rate per 100,000 males Landis et al 1998

  5. Prostate Cancer Risk Factors • Age: After age 50, the incidence and number of deaths increase almost exponentially • Family history: Male relatives of patients with prostate cancer have a higher incidence of PC. • Race:African-American men have a higher incidence of PC when compared with Caucasian-American men; • Asian men have the lowest incidence.

  6. Prostate Cancer Risk Factors • Dietary fat: High intake of fat is associated with increased incidence of prostate cancer. • Endogenous level of androgenic hormones: Levels of androgenic hormones play a role in the development of prostate cancer.

  7. Prostate Cancer Risk Factors Gene HPC1 PCaP HPCX Location 1q24-25 1q42.2-43 Xq27-28 Family numberstested for linkage 91 47 360 HPC1, Hereditary Prostate Cancer 1 PCaP, Predisposing for Prostate Cancer HPCX, Hereditary Prostate Cancer X Berthon et al 1998 Smith et al 1996 Xu et al 1998

  8. Study location and dates Canada 1986-1996 Austria 1993-1998 Europe 1998- (ERSPC trial) USA 1993- (PLCO trial) No. patients 46,732 21,079 113,194 74,000 Effect of screeningon mortality 69%** 42%* Data availableafter 2005 Data availableafter 2005   *p<0.05 **p<0.01 Screening For Prostate Cancer Bartsch et al 2000Gohagan et al 1994 Labrie et al 1999 Schröder et al 1999

  9. Prostate Gland Anatomy

  10. Bladder Seminal vesicle Urethra Ejaculatoryduct Penis Prostate Testis Relationship of Prostate to Urogenital Tract

  11. Anatomy of the prostate gland B CZ Central zone PZ Peripheral zone PPS Pre-prostaticsphincter SV SV PPS VAS VAS U Urethra U V Verumontanum CZ CZ Ejaculatoryduct ED ED ED V VAS Vas deferens Seminal vesicles PZ SV PZ B Bladder

  12. Prostate Cancer: Staging System Stage A: Clinically Unsuspected Disease A1: Focal carcinoma, usually well differentiated A2: Diffuse carcinoma, usually poorly differentiated Stage B: Tumor Confined to Prostate Gland B1: Small, discrete nodule in one lobe of gland B2: Large or multiple nodules or areas of involvement

  13. Prostate Cancer: Staging System Stage C: Tumor Localized to the Periprostatic Area C1: Tumor outside prostatic capsule, estimated weight <70 g, seminal vesicles uninvolved C2: Tumor outside prostatic capsule, estimated weight >70 g, seminal vesicles involved Stage D: Metastatic Prostate Cancer D1: Pelvic lymph node metastases and/or urethral obstruction causing hydronephrosis D2: Bone, soft tissue, organ, or distant lymph node metastases

  14. Gleasongrade1 2 3 4 5 Histological grading: Gleason system Kirby 1999

  15. T1a T2a T1b T2b T3a T1c Gleason Score and Serum PSAPredictors of Organ Confined Cancer 1.0 Gleason score 5 Clinical stage 0.8 Probability oforgan-confinedcancer 0.6 0.4 0.2 0 PSA (ng/mL) 1.0 Probability of organ-confinedcancer 0.8 Gleason scores 8-10 0.6 0.4 0.2 0 0 4 10 20 PSA (ng/mL) Partin et al 1997

  16. Diagnosis: Transrectal Ultrasound

  17. Prostate Cancer Prognostic Factors Local Disease • Clinical stage • Tumor grade (Gleason Score) • Serum PSA Advanced Disease • Performance status • Metastatic disease sites • Tumor grade (Gleason Score) • Serum PSA

  18. Cancer-Specific and DFS by Tumor Grade & Stage StageCancer-SpecificEstimate Rate Survival Rate (%)of Lifelong DFS (%) T1a 98 95 T1b 90 80 T1c 90 80 T2 grade 1– 2 91 65 T2 grade 3 66 65 T3 60 25 N+ 40 >5 M+ 10 >1

  19. Treatment Approach Five modality of treatment: • Radical Prostatectomy • Brachytherapy • External irradiation • Hormonotherapy • Wait and watch

  20. Treatment ApproachEarly-Stage Prostate Disease Five modality of treatment: • Radical Prostatectomy • Brachytherapy • External irradiation • Hormonotherapy • Wait and watch

  21. Radical Prostatectomy • Definitive therapy for localized disease • Results excellent for low-volume disease • Most definitive staging: pathologic tissue examination of prostate, seminal vesicles and lymph nodes • Possible to treat with radiation if relapse is local

  22. Radical Prostatectomy: Results 2,758 patients with T1-2,Nx,M0 10-Year survival Specific Metastatic-free Grade I: 94 (87 - 98) 87 (78 - 92) Grade II: 80 (74 - 85) 68 (62 - 73) Grade III: 77 (65 - 86) 52 (38 - 64) JAMA 1966

  23. Radical Prostatectomy • Major surgery with general anaesthesia • Blood loss and need for transfusion • Impotence • Urinary incontinence • Positive surgical margins

  24. Radical Prostatectomy: Positive Surgical Margins By Clinical Stage Clinical Stage No. PtsNo. (%) Tia 32 0 (0) T1b 38 10 (26) T1c 43 3 (7) T2a 96 11 (11) T2b 156 34 (22) T2c 113 20 (18) Total47878 (16)

  25. Treatment ApproachEarly-Stage Prostate Disease Five modality of treatment: • Radical Prostatectomy • Brachytherapy • External irradiation • Hormonotherapy • Wait and watch

  26. מהי רדיותרפיה • זהו תחום רפואי באונקולוגיה • הרדיותרפיה משתמשת בקרינה מייננת - פוטונים, אלקטרונים, פרוטונים ונויטרונים לטיפול במחלות סרטניות. בעיקר אך גם במחלות שפירות. • העיקרון הבסיסי הוא מתן קרינה לאיבר המטרה במינון המספיק להשמיד את כל תאי הסרטן, מבלי לגרום לנזק לרקמות ולאיברים הבריאים שמסביב לגידול

  27. Radiotherapy for Localized Prostate Cancer טיפול קרינתי חיצוניTeletherapy • מקור הקרינה הוא במרחק מסוים מהחולה • מקור הקרינה חומר רדיואקטיבי (קובלט 60) • מקור הקרינה מכונות המייצרות (מאיצים קוויים) טיפול קרינתי פנימיBrachytherapy • מקור הקרינה מושתל באיבר המטרה, לתקופה זמנית או קבועה • מקורות הקרינה הם חומרים רדיואקטיביים

  28. Prostate Brachytherapy Source: I-125 T1/2: 59.6 days Photon energy: 27- 35 KeV ( and X-rays) HVL: 0.025mm Lead

  29. Prostate Brachytherapy

  30. Prostate Brachytherapy

  31. Criteria for I-125 Implant • Serum PSA < 10ng/ml • Gleason score < 7 • T stage = T1-T2 • Gland volume < 50cc • No previous TURP • No evidence of metastatic disease • International Prostatic System Score < 15

  32. Prostate I-125 ImplantResults: 5-year Biochemical Outcome Pre-Tr. Gleason5-year PSAScore PRFS Favorable risk:<10 <6 88% Intermediate-risk>10 or >6 77% Unfavorable-risk>10 & >6 38% I-125 implant only:77% I-125 implant & TAB (2months):100% Morbidity:Urinary morbidity, Urinary incontinence Rectal bleeding and Erectile dysfunction

  33. Treatment ApproachEarly-Stage Prostate Disease Five modality of treatment: • Radical Prostatectomy • Brachytherapy • External irradiation • Hormonotherapy • Wait and watch

  34. External irradiation

  35. External irradiation

  36. Results of External Irradiation ‎ Results: 10-year • DFS for local failure 87% • DFS for metastatic failure 79% • Free of any failure 67% • Cause-specific survival 86% Results equal to radical prostatectomy

  37. Results by Tumor Stage T1-2,No T3,N0T1-3,N1 Local control:92%60% 45% Survival:75%22% 6%

  38. Radiotherapy and Hormonal Therapy for Prostate Cancer XRT XR‎T+HT .p value Local control: 80 98 <0.001 Systemic control: 60 90 <0.001 Overall survival: 40 60 <0.001

  39. Postoperative radiotherapy in pT3 prostate cancer Indications: • Positive surgical margins • Capsular perforation • Seminal vesicle invasion • Treatment: • Dose: 60Gy/30 fractions/6 weeks • Volume:“Prostate & seminal vesicle”

  40. External Beam Radiation for Localized Prostate Cancer Advantages • Results excellent for low-volume disease • Impotence and incontinence significantly less than with radical prostatectomy • Dose not require general anesthesia or involve blood loss

  41. External Beam Radiation for Localized Prostate Cancer Disadvantages • Radiation injury to bladder and rectum • Clinical staging • 7 weeks for treatment • High risk of failure in stage T3 disease • Difficulty in performing surgery as salvage operation after radiation therapy

  42. Treatment Approach Five modality of treatment: • Radical Prostatectomy • Brachytherapy • External irradiation • Hormonotherapy • Wait and watch

  43. Hormonotherapy • The principle of hormonal therapy in prostate cancer is to block the effects of dihydrotestosterone on tumor cells • 1914 Huggins C: • Tested the effect of castration, estrogen and androgen on serum acid phosphatase in metastatic carcinoma of the prostate.

  44. Hormonal inhibition of prostatic cancer Adrenal gland Hypothalamus Mevalonic acid Cholesterol Androstenedione TestosteroneEstrogen GN-RH + Pituitary LH + + Testis Testosterone receptor Testosterone DTH

  45. First-Line Therapy in Advanced Prostate Cancer: Androgen Ablation Surgical castration:Orchiectomy Medical castration • Estrogens: Diethylstilbestrol • Luteinizing Hormone–Releasing Hormone analogs: Leuprolide (Leupron) Goserelin (Zoladex) Buserelin (Suprafact) Triptorelin (Decapeptyl) 1971 Schally AV: Isolation and properties of the FSH and LH releasing hormone.

  46. Hormonal inhibition of prostatic cancer Adrenal gland Hypothalamus Decapepty (D-Tro6LHRH) Mevalonic acid Cholesterol Androstenedione TestosteroneEstrogen Zoladex (Goserelin) GN-RH Superfact (Buserelin) + Pituitary LH + + Testis Testosterone Testosterone receptor DTH

  47. Antiandrogens Drugs • Steroidal antiandrogens Cyproterone acetate (Androcur/Armacor) • Nonsteroidal antiandrogens Flutamide (Eulexin) Nilutamide (Anandron) Biclutamide (Casodex)

  48. Hormonal inhibition of prostatic cancer Adrenal gland Hypothalamus Mevalonic acid Cholesterol Androstenedione TestosteroneEstrogen GN-RH + Pituitary LH Eulexin flutamide + Androcur Cyproterone Acetate Casodex Bicalutamide + Testis Testosterone DTH Testosterone receptor

  49. Agents resulting in adrenal suppression • Aminoglutethimide (Orimetene) • Ketoconazole (Nizoral

  50. Hormonal inhibition of prostatic cancer Adrenal gland Hypothalamus Decapepty (D-Tro6LHRH) Mevalonic acid Cholesterol Androstenedione TestosteroneEstrogen Zoladex (Goserelin) Aminogluthetimide GN-RH Superfact (Buserelin) + Pituitary LH Eulexin flutamide + Androcur Cyproterone Acetate Casodex Bicalutamide + Testis Testosterone DTH Testosterone receptor

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