Prostate Cancer. Dr. Andres Wiernik PDF Free Download

Prostate Cancer Dr. Andres Wiernik 2017

Objectives YES!!! 1. Epidemiology 2. Biology or Natural History of Prostate Cancer 3. Treatment NO!!! 1. Prostate Cancer Screening - controversies

Which is the most common cancer diagnosed in men? 1. Lung 2. Prostate 3. Colon 4. Pancreas 5. Lymphoma

What % of newly diagnosed Prostate Cancer patients are alive at 5 years? 1. 5% 2. 25% 3. 50% 4. 75% 5. 99%

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

Epidemiology

Prostate Cancer 2014

Prostate Cancer 2016

Risk Factors for Prostate Cancer Gender Age Race Family History (father, brother or son) Hormones Vitamin E supplementation

35 533 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

Vitamin E vs Placebo p = 0.008

Dr. Wiernik is there anything I can take to prevent Prostate Cancer? GnRH Finasteride 5 Alpha Reductase INHIBITOR

The Prostate Cancer Prevention Trial Finasteride vs Placebo NEJM Aug 2003

NEJM Aug 2013

Finasteride as Cancer Prevention I do NOT recommend Finasteridefor prostate cancer prevention

Biology and Natural History of Prostate Cancer

Diagnosis of Prostate Cancer Localized disease (or locally advanced) 90-95% Metastatic Disease Stage IV 5-10%

Prostate Cancer 2016

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

Case: Mr. C Biopsy Results Gleason score: 4 + 4 = 8/10, 4 of 4 cores in the right mid (50%) and right base (80%) Staging: ct1c PSA level: 8

Donald Gleason

GLEASON GRADE

Localized Prostate Cancer: Risk Stratification 1. Localized vs Locally Advanced? 2. PSA level? 3. Gleason Score?

Case: Mr. C Age at Diagnosis % Alive % Deceased Years Following Diagnosis JAMA 2005 Albertsen, et al

Localized Prostate Cancer: Risk Stratification LOW RISK Intermediate RISK HIGH RISK PSA 10 PSA 10-20 PSA > 20 Gleason 6 Gleason 7 Gleason 8 T2a or smaller T2b T2cor greater Determine Life Expectancy Active Surveillance vs Treatment

Treatment options for Localized Prostate CA 1. Radical Prostatectomy 2. XRT External Beam RT / EBRT Brachytherapy 3. Active Surveillance

Case: Mr. C PSA level 2 years Time

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

Case: Mr. C PSA level 2 years 7 years Time

What is your next step in management? 1. Lupron 2. Lupron + Casodex 3. Chemotherapy 4. Radiation Therapy 5. Zometa

Prostate Cancer Localized disease (or locally advanced) Metastatic Disease Stage IV

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

Case: Mr. C PSA level ADPC Androgen Dependent Prostate Cancer 2 years 7 years Time

GnRH

Case: Mr. C PSA level 2 years 7 years Time

Case: Mr. C PSA level 2 years 7 years 8 years Time

Case: Mr. C Castration Resistant Prostate Cancer PSA level 2 years 7 years 8 years Time

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

CRPC Castration Resistant Prostate Cancer How does the tumor survive with low levels of Androgen? Tumor-produced androgens via 17-20 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;10:33-39. 2. Zaplin ME, et al. J Clin Oncol. 2003;21:2673-2678. 3. Pienta KJ, et al. Clin Cancer Res. 2006;12:1665-1671. 4. Tzelepi V et al Clin Cancer Res 2012;18:666-77

Abiraterone prior to Chemo NEJM, 2013

Enzalutamide prior to Chemo NEJM, 2014

Chemotherapy in CRPC NEJM, 2004

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

Sipulecel T- (PROVENGE)

Sipulecel T- (PROVENGE) Median OS improved by 4.1 months p= 0.03 Cost: $93 000 NEJM, 2014

Radium-223 NEJM, 2013

Radium-223

Case: Mr. C ADPC CRPC Death PSA level 2 years 7 years 8 years Time 10-15 years?

ASCO 2014 Why not treat with chemotherapy up front? Patients with newly diagnosed metastatic Prostate Cancer Docextal vs ADT

NEJM 2015

Thank You! Andres Wiernik awiernik@gmail.com

Prostate Cancer. Dr. Andres Wiernik 2017