Prostate Cancer. Dr. Andres Wiernik 2017
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1 Prostate Cancer Dr. Andres Wiernik 2017
2 Objectives YES!!! 1. Epidemiology 2. Biology or Natural History of Prostate Cancer 3. Treatment NO!!! 1. Prostate Cancer Screening - controversies
3 Which is the most common cancer diagnosed in men? 1. Lung 2. Prostate 3. Colon 4. Pancreas 5. Lymphoma
4 What % of newly diagnosed Prostate Cancer patients are alive at 5 years? 1. 5% 2. 25% 3. 50% 4. 75% 5. 99%
5 Which of the following is NOT a risk factor for Prostate Cancer? Age over 50 African-American Father with history of Prostate Cancer Vitamin E supplementation Finasteride
6 Epidemiology
7 Prostate Cancer 2014
8 Prostate Cancer 2016
9 Prostate Cancer 2016
10 Prostate Cancer 2016
11 Prostate Cancer 2016
12 Prostate Cancer 2016
13 Prostate Cancer 2016
14 Prostate Cancer 2016
15 Risk Factors for Prostate Cancer Gender Age Race Family History (father, brother or son) Hormones Vitamin E supplementation
16 men in 427 sites in USA, Canada Puerto Rico PSA less than 4 ng/ml 55 or older (50 or older if Black) 4 arms: Selenium 200 ug/day Vit E 400 IU / day Vit E + Selenium Placebo Followed for 7-12 years
17 Vitamin E vs Placebo p = 0.008
18 Dr. Wiernik is there anything I can take to prevent Prostate Cancer? GnRH Finasteride 5 Alpha Reductase INHIBITOR
19 The Prostate Cancer Prevention Trial Finasteride vs Placebo NEJM Aug 2003
20 NEJM Aug 2013
21 Finasteride as Cancer Prevention I do NOT recommend Finasteridefor prostate cancer prevention
22 Biology and Natural History of Prostate Cancer
23 Diagnosis of Prostate Cancer Localized disease (or locally advanced) 90-95% Metastatic Disease Stage IV 5-10%
24 Prostate Cancer 2016
25 Case: Classic Clinic Patient Mr. C is a 55-year-old African American male who you see in clinic BMI 35 kg/m 2 PSA 2 years ago was 4 ng/ml, now 8 ng/ml Asymptomatic Comorbidities: hypertension and diabetes Digital rectal exam shows 30-gram prostate without nodules A Pelvic MRI shows evidence of T1 lesion No LN involvement
26
27 Case: Mr. C Biopsy Results Gleason score: = 8/10, 4 of 4 cores in the right mid (50%) and right base (80%) Staging: ct1c PSA level: 8
28 Donald Gleason
29 GLEASON GRADE
30 Localized Prostate Cancer: Risk Stratification 1. Localized vs Locally Advanced? 2. PSA level? 3. Gleason Score?
31 Case: Mr. C Age at Diagnosis % Alive % Deceased Years Following Diagnosis JAMA 2005 Albertsen, et al
32 Localized Prostate Cancer: Risk Stratification LOW RISK Intermediate RISK HIGH RISK PSA 10 PSA PSA > 20 Gleason 6 Gleason 7 Gleason 8 T2a or smaller T2b T2cor greater Determine Life Expectancy Active Surveillance vs Treatment
33 Treatment options for Localized Prostate CA 1. Radical Prostatectomy 2. XRT External Beam RT / EBRT Brachytherapy 3. Active Surveillance
34 Case: Mr. C PSA level 2 years Time
35 Case: Mr. C Mr. C returns to your clinic 7 year surveillance. Wife: He has been complaining of back pain for 4 weeks His PSA is 80 Bone Scans and CT C/A/P show evidence of diffuse metastatic disease in the spine Biopsy: Metastatic Prostate Cancer
36 Case: Mr. C PSA level 2 years 7 years Time
37 What is your next step in management? 1. Lupron 2. Lupron + Casodex 3. Chemotherapy 4. Radiation Therapy 5. Zometa
38 Prostate Cancer Localized disease (or locally advanced) Metastatic Disease Stage IV
39 Prostate Cancer: Treatment Menu ADPC Appetizer : 1- Surgical Castration $ 2. Medical Castration $$$ - GnRH Agonist - Leuprolide (Lupron) - GnRH Antagonist - Degarelix - Non-esteroidal Antiandrogen - Bicalutamide (Casodex) $$ - Flutamide (Eulexin) $$ Side Orders: Prevention of SRE: - Biphosphanate Therapy - Denosumab Palliative Care CRPC Entrée : 1- Antiandrogens - Nonsteroidal Antiandrogen $$ - Bicalutamide (Casodex) - Flutamide (Eulexin) - Ketoconazol $ - CYP 17 inhibitors $$$ - Abiraterone - AR Antagonists $$$ - Enzalutamide 2. Chemotherapy $$ - Docetaxel - Cabazitaxel 3. Immunotherapy $$$$ - Sipulecel T 4. Radium 223 $$$ Palliative Radiation
40 Case: Mr. C PSA level ADPC Androgen Dependent Prostate Cancer 2 years 7 years Time
41 Prostate Cancer: Treatment Menu ADPC Appetizer : 1- Surgical Castration $ 2. Medical Castration $$$ - GnRH Agonist - Leuprolide (Lupron) - GnRH Antagonist - Degarelix - Non-esteroidal Antiandrogen - Bicalutamide (Casodex) $$ - Flutamide (Eulexin) $$ Side Orders: Prevention of SRE: - Biphosphanate Therapy - Denosumab Palliative Care CRPC Entrée : 1- Antiandrogens - Nonsteroidal Antiandrogen $$ - Bicalutamide (Casodex) - Flutamide (Eulexin) - Ketoconazol $ - CYP 17 inhibitors $$$ - Abiraterone - AR Antagonists $$$ - Enzalutamide 2. Chemotherapy $$ - Docetaxel - Cabazitaxel 3. Immunotherapy $$$$ - Sipulecel T 4. Radium 223 $$$ Palliative Radiation
42 GnRH
43 Case: Mr. C PSA level 2 years 7 years Time
44 Case: Mr. C PSA level 2 years 7 years 8 years Time
45 Case: Mr. C Castration Resistant Prostate Cancer PSA level 2 years 7 years 8 years Time
46 Hypothesis: Androgen Deprivation Therapy - ADT ( Castration ) ADPC Androgen Dependent Prostate Cancer CRPC Castration Resistant Prostate Cancer Androgen Deprivation 2-10 years êpsa é PSA é PSA
47
48 Hypothesis: Androgen Deprivation Therapy - ADT ( Castration ) ADPC Androgen Dependent Prostate Cancer CRPC Castration Resistant Prostate Cancer Androgen Deprivation 2-10 years êpsa é PSA é PSA
49 CRPC Castration Resistant Prostate Cancer How does the tumor survive with low levels of Androgen? Tumor-produced androgens via lyase upregulation can promote survival/growth when: Increased AR expression 1 Genetic alterations in AR 2 Increased AR cofactor expression levels 3 Wow!!! Total AR independence Absence of all AR production and signaling in 25% of all post-chemotherapy pts 4 1. Chen CD, et al. Nature Med. 2004;10: Zaplin ME, et al. J Clin Oncol. 2003;21: Pienta KJ, et al. Clin Cancer Res. 2006;12: Tzelepi V et al Clin Cancer Res 2012;18:666-77
50 Prostate Cancer: Treatment Menu ADPC Appetizer : 1- Surgical Castration $ 2. Medical Castration $$$ - GnRH Agonist - Leuprolide (Lupron) - GnRH Antagonist - Degarelix - Non-esteroidal Antiandrogen - Bicalutamide (Casodex) $$ - Flutamide (Eulexin) $$ Side Orders: Prevention of SRE: - Biphosphanate Therapy - Denosumab Palliative Care CRPC Entrée : 1- Antiandrogens - Nonsteroidal Antiandrogen $$ - Bicalutamide (Casodex) - Flutamide (Eulexin) - Ketoconazol $ - CYP 17 inhibitors $$$ - Abiraterone - AR Antagonists $$$ - Enzalutamide 2. Chemotherapy $$ - Docetaxel - Cabazitaxel 3. Immunotherapy $$$$ - Sipulecel T 4. Radium 223 $$$ Palliative Radiation
51
52
53 Abiraterone prior to Chemo NEJM, 2013
54 Prostate Cancer: Treatment Menu ADPC Appetizer : 1- Surgical Castration $ 2. Medical Castration $$$ - GnRH Agonist - Leuprolide (Lupron) - GnRH Antagonist - Degarelix - Non-esteroidal Antiandrogen - Bicalutamide (Casodex) $$ - Flutamide (Eulexin) $$ Side Orders: Prevention of SRE: - Biphosphanate Therapy - Denosumab Palliative Care CRPC Entrée : 1- Antiandrogens - Nonsteroidal Antiandrogen $$ - Bicalutamide (Casodex) - Flutamide (Eulexin) - Ketoconazol $ - CYP 17 inhibitors $$$ - Abiraterone - AR Antagonists $$$ - Enzalutamide 2. Chemotherapy $$ - Docetaxel - Cabazitaxel 3. Immunotherapy $$$$ - Sipulecel T 4. Radium 223 $$$ Palliative Radiation
55
56 Enzalutamide prior to Chemo NEJM, 2014
57 Prostate Cancer: Treatment Menu ADPC Appetizer : 1- Surgical Castration $ 2. Medical Castration $$$ - GnRH Agonist - Leuprolide (Lupron) - GnRH Antagonist - Degarelix - Non-esteroidal Antiandrogen - Bicalutamide (Casodex) $$ - Flutamide (Eulexin) $$ Side Orders: Prevention of SRE: - Biphosphanate Therapy - Denosumab Palliative Care CRPC Entrée : 1- Antiandrogens - Nonsteroidal Antiandrogen $$ - Bicalutamide (Casodex) - Flutamide (Eulexin) - Ketoconazol $ - CYP 17 inhibitors $$$ - Abiraterone - AR Antagonists $$$ - Enzalutamide 2. Chemotherapy $$ - Docetaxel - Cabazitaxel 3. Immunotherapy $$$$ - Sipulecel T 4. Radium 223 $$$ Palliative Radiation
58 Chemotherapy in CRPC NEJM, 2004
59 Prostate Cancer: Treatment Menu ADPC Appetizer : 1- Surgical Castration $ 2. Medical Castration $$ - GnRH Agonist - Leuprolide (Lupron) $$ - GnRH Antagonist - Degarelix $$$ Side - Non-esteroidal Orders: Antiandrogen - Bicalutamide (Casodex) Prevention $$ of SRE: - Biphosphanate - Flutamide Therapy (Eulexin) - Denosumab $$ Palliative Care Palliative Radiation CRPC Entrée : 1- Antiandrogens - Nonsteroidal Antiandrogen $$ - Bicalutamide (Casodex) - Flutamide (Eulexin) - Ketoconazol $ - CYP 17 inhibitors $$$ - Abiraterone - AR Antagonists $$$ - Enzalutamide 2. Chemotherapy $$ - Docetaxel - Cabazitaxel 3. Immunotherapy
60 Prostate Cancer: Treatment Menu ADPC Appetizer : 1- Surgical Castration $ 2. Medical Castration $$$ - GnRH Agonist - Leuprolide (Lupron) - GnRH Antagonist - Degarelix - Non-esteroidal Antiandrogen - Bicalutamide (Casodex) $$ - Flutamide (Eulexin) $$ Side Orders: Prevention of SRE: - Biphosphanate Therapy - Denosumab Palliative Care CRPC Entrée : 1- Antiandrogens - Nonsteroidal Antiandrogen $$ - Bicalutamide (Casodex) - Flutamide (Eulexin) - Ketoconazol $ - CYP 17 inhibitors $$$ - Abiraterone - AR Antagonists $$$ - Enzalutamide 2. Chemotherapy $$ - Docetaxel - Cabazitaxel 3. Immunotherapy $$$$ - Sipulecel T 4. Radium 223 $$$ Palliative Radiation
61 Sipulecel T- (PROVENGE)
62 Sipulecel T- (PROVENGE) Median OS improved by 4.1 months p= 0.03 Cost: $ NEJM, 2014
63 Prostate Cancer: Treatment Menu ADPC Appetizer : 1- Surgical Castration $ 2. Medical Castration $$$ - GnRH Agonist - Leuprolide (Lupron) - GnRH Antagonist - Degarelix - Non-esteroidal Antiandrogen - Bicalutamide (Casodex) $$ - Flutamide (Eulexin) $$ Side Orders: Prevention of SRE: - Biphosphanate Therapy - Denosumab Palliative Care CRPC Entrée : 1- Antiandrogens - Nonsteroidal Antiandrogen $$ - Bicalutamide (Casodex) - Flutamide (Eulexin) - Ketoconazol $ - CYP 17 inhibitors $$$ - Abiraterone - AR Antagonists $$$ - Enzalutamide 2. Chemotherapy $$ - Docetaxel - Cabazitaxel 3. Immunotherapy $$$$ - Sipulecel T 4. Radium 223 $$$ Palliative Radiation
64
65
66 Radium-223 NEJM, 2013
67 Radium-223 NEJM, 2013
68 Radium-223
69 Case: Mr. C ADPC CRPC Death PSA level 2 years 7 years 8 years Time years?
70
71
72
73 ASCO 2014 Why not treat with chemotherapy up front? Patients with newly diagnosed metastatic Prostate Cancer Docextal vs ADT
74 NEJM 2015
75 NEJM 2015
76 Thank You! Andres Wiernik
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