1. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Prostate Cancer

2. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Incidence PROSTATE CANCER Incidence *Incidence per 100,000 population. Parkin DM, et al. CA Cancer J Clin. 1999;49:53. 39.5516.758.5149.701.085.1331.0392.39 EasternEurope Japan Australia New Zealand China NorthAfrica SouthAfrica NorthAmerica Western Europe Europe

3. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria 5-year survival rates PROSTATE CANCER 5-year survival rates 49%22%52%63%40%40%41%79% SouthEurope Japan Australia New Zealand China NorthAfrica Sub-SaharanAfrica NorthAmerica Northwestern Europe Europe Parkin DM, et al. CA Cancer J Clin. 1999;49:37. Estimated 5-Year Survival (%).

4. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria 5-year survival by stage PROSTATE CANCER 5-year survival by stage Greenlee RT, et al. CA Cancer J Clin. 2001;51:15-36.

5. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Genetic events in prostate carcinogenesis PROSTATE CANCER Genetic events in prostate carcinogenesis Abeloff M, et al. Clinical Oncology. 1995;1439. Normal prostate Histologic prostate cancer Localized prostate cancer Metastatic prostate cancer Androgen-independent prostate cancer Tumor suppressor gene inactivation p53 gene inactivation H-ras oncogene overexpression bcl-2 oncogene overexpression Metastasis gene suppressor inactivation Decreased adhesion molecule expression Retinoblastoma gene loss

6. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Risk factors PROSTATE CANCER Risk factors Age Diet Family history Race Environmental factors Parkin DM, et al. CA Cancer J Clin. 1999;49:33-64. Carroll PR, et al. Cancer: Principles & Practice of Oncology. 6th ed. 2001;1418-1479.

7. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Screening PROSTATE CANCER Screening Advantages Early disease highly curable; advanced disease generally incurable Screening relatively simple Routine PSA and DRE Disadvantages Value of screening not proven Suboptimal sensitivity, specificity, predictive value of tests (DRE, PSA, TRUS) Not all prostate cancers clinically significant: Psychological and economic burden of diagnosis Morbidity of potentially unnecessary treatment Oesterling J, et al. Cancer: Principles & Practice of Oncology. 5th ed. 1997;1322-1386. Carroll PR, et al. Cancer: Principles & Practice of Oncology. 6th ed. 2001;1418-1479. Rimer BK, et al. Cancer: Principles & Practice of Oncology. 6th ed. 2001;.627-640.

8. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Screening tools PROSTATE CANCER Screening tools Rimer BK, et al. Cancer: Principles & Practice of Oncology. 6th ed. 2001;627-640. Method Sensitivity (%) Specificity (%) Positive Predictive Value (%) DRE45-8445-9721-43 PSA67-8248-8232-48 TRUS77-9227-9415-54

9. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Prostate specific antigen (PSA) PROSTATE CANCER Prostate specific antigen (PSA) Single-chain glycoprotein Produced by prostate epithelial cells; secreted into prostatic lumen Blood level of <4 ng/mL considered normal PSA 4-10 ng/mL associated with 22% positive biopsy rate PSA >10 ng/mL associated with 66% positive biopsy rate Elevated by any prostate disease, prostate manipulation, medication Used for staging, monitoring, prognosis Oesterling J, et al. Cancer: Principles & Practice of Oncology. 5th ed. 1997;1322-1386. Kelly WK, Dodd PM. The American Cancer Society Textbook of Clinical Oncology. 3rd ed. 2001;427-435. Brawer MK. CA Cancer J Clin. 1999;49:264-281.

10. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Improving accuracy of PSA PROSTATE CANCER Improving accuracy of PSA PSA density –Serum PSA level/prostate volume PSA velocity –Change in serum PSA over time Age-adjusted PSA –Different cutoff levels for different age groups Prostate-specific–membrane antigen (PSMA) Free-to-total PSA –Measurement of free and complexed circulating PSA None of these tests has a role in routine management Brawer MK. CA Cancer J Clin. 1999;49:264-281.

11. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Free-to-total PSA* PROSTATE CANCER Free-to-total PSA* PSAProbability of Cancer 2 ng/mL1% 2-4 ng/mL15% 4-10 ng/mL25% >10 ng/mL>50% Brawer MK. Prostate-specific antigen: Current status. CA Cancer J Clin. 1999;49(5):264-281. % FPSAProbability of Cancer 0-10%56% 10-15%28% 15-20%20% 20-25%16% >25%8% *Men with non-suspicious DRE results, regardless of patient age.

12. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Screening and Diagnosis PROSTATE CANCER Screening and Diagnosis Carroll PR, et al. Cancer: Principles & Practice of Oncology. 6th ed. 2001;1418-1479. Initial Evaluation Screening Results Follow-up DRE + total PSA DRE negative and Annual DRE/PSA PSA normal Counseling for DRE negative with: prostate cancer - PSA >10 ng/mL - TRUS biopsy screening - PSA 4-10 mg/mL - TRUS biopsy or % free PSA - Abnormal age- - Consider TRUS biopsy referenced PSA Family history DRE positive and TRUS biopsy History of prostate PSA normal or positive disease Medication/supplements Prior PSA/DRE

13. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Stage at diagnosis PROSTATE CANCER Stage at diagnosis 5% 35% 60% 0 10 20 30 40 50 60 70 LocalizedRegionalDistant Stage % of Cases Kassabian VS, et al. The American Cancer Society Textbook of Clinical Oncology. 2nd ed. 1995;311-318. Zinner NR, et al. Everyone’s Guide to Cancer Therapy. 1997;634-649.

14. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Oesterling J, et al. Cancer: Principles & Practice of Oncology. 5th ed. 1997;1322-1386. Signs and symptoms PROSTATE CANCER Signs and symptoms Early Disease Peripheral zone: none Transition zone: –Urinary hesitancy, frequency, urgency –Decreased force of urine stream –Nocturia Progressive Disease Hematospermia Decreased ejaculate volume Impotence Advanced Disease Bone pain

15. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Pathological classification PROSTATE CANCER Pathological classification Epithelial Neoplasms Adenocarcinomas –Pure ductal –Mucinous Small cell tumors Transitional cell carcinomas Carcinoma in situ (intraepithelial neoplasia) and precursors of neoplasiaCarcinosarcomas Nonepithelial Neoplasms Mesenchymal—benign and malignant Lymphoma Germ Cell Tumors Oesterling J, et al. Cancer: Principles & Practice of Oncology. 5th ed. 1997;1322-1386.

16. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Tumor distribution PROSTATE CANCER Tumor distribution Oesterling J, et al. Cancer: Principles & Practice of Oncology. 5th ed. 1997;1322-1386.

17. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria PROSTATE CANCER Local extension

18. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Lymphatic spread PROSTATE CANCER Lymphatic spread

19. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Distant metastatic spread PROSTATE CANCER Distant metastatic spread

20. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Stages PROSTATE CANCER Stages AJCC ® Cancer Staging Manual, 5th edition (1997) published by Lippincott-Raven Publishers, Philadelphia, Pennsylvania. Stage IT1aN0M0G1 Stage IIT1aN0M0G2,3-4 T1bN0M0Any G T1cN0M0Any G T1N0M0Any G T2N0M0Any G Stage IIIT3N0M0Any G Stage IVT4N0M0Any G Any TN1M0Any G Any TN2M0Any G Any TN3M0Any G Any TAny NM1Any G

21. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Stage I PROSTATE CANCER Stage I AJCC ® Cancer Staging Manual, 5th edition (1997) published by Lippincott-Raven Publishers, Philadelphia, Pennsylvania.

22. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Stage II PROSTATE CANCER Stage II AJCC ® Cancer Staging Manual, 5th edition (1997) published by Lippincott-Raven Publishers, Philadelphia, Pennsylvania.

23. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Stage II (cont’d) PROSTATE CANCER Stage II (cont’d) AJCC ® Cancer Staging Manual, 5th edition (1997) published by Lippincott-Raven Publishers, Philadelphia, Pennsylvania. *Note: Tumor found in one or both lobes by needle biopsy, but not palpable or reliably visible by imaging, classified as T1c.

24. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Stage III PROSTATE CANCER Stage III AJCC ® Cancer Staging Manual, 5th edition (1997) published by Lippincott-Raven Publishers, Philadelphia, Pennsylvania. *Note: Invasion into the prostatic apex or into (but not beyond) the prostatic capsule is not classified as T3, but as T2.

25. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Stage IV PROSTATE CANCER Stage IV AJCC ® Cancer Staging Manual, 5th edition (1997) published by Lippincott-Raven Publishers, Philadelphia, Pennsylvania.

26. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Prognostic factors for advanced disease PROSTATE CANCER Prognostic factors for advanced disease Presence of symptoms Performance status Location and extent of disease Number of lesions on bone scan Serum testosterone and alkaline phosphatase levels Carroll PR, et al. Cancer: Principles & Practice of Oncology. 6th ed. 2001;1418-1479.

27. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria PROSTATE CANCER Commonly used therapies Disease StageTreatment Stage I/IIRadical prostatectomy (if <70 years old and healthy); Radiation (if >70 years old and healthy); or Watchful waiting (if < 10 year life expectancy, significant comorbidity, or unfavorable tumor characteristics) Stage IIIRadiation therapy or surgery (in rare cases) plus adjuvant hormonal therapy Stage IVPharmacologic castration (LHRH analogues, antiandrogens) HRPCAntiandrogen withdrawal or continued testicular androgen deprivation; Second-line hormonal therapy; Chemotherapy; or Radiation therapy

28. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Response to surgery PROSTATE CANCER Response to surgery Diagnosis of Stage I/II disease (45% to 55% of new prostate cancer diagnoses) SURGERY 85% Respond Without Further Intervention and Achieve a Disease-Free Status 15% Fail to Respond, Developing Stage III/IV Disease Within 1 Year

29. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Risk factors for biochemical failure PROSTATE CANCER Risk factors for biochemical failure Rising serum PSA levels after definitive local therapy are indicative of recurrence Pretreatment disease characteristics predictive of poor outcome following curative-intent prostatectomy: Clinical stage T3 or T4 disease Serum PSA levels >20 ng/mL Poorly differentiated histology (ie, biopsy Gleason score  8) D’Amico AV, et al. JAMA. 1998;280:969-974.

30. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Response to hormonal therapy PROSTATE CANCER Response to hormonal therapy Enter Hormone- Refractory Status (Median Survival = 6 to 12 months from time of diagnosis) 20% Achieve a Disease-Free Status and Terminate Therapy Diagnosis of Stage III/IV disease (45% to 55% of new prostate cancer diagnoses) HORMONAL THERAPY 85% Respond (ie, PSA decline  50%) 15% Fail to Respond 80% Respond While Continuing Therapy (Mean Response Duration = 3 Years)