17/07/2014. Prostate Cancer Watchful Waiting New Treatments Andrew Williams Urologist and Urological Oncologist ADHB, CMDHB and 161 Gillies Ave, Epsom

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1 My Biases Prostate Cancer Watchful Waiting New Treatments Andrew Williams Urologist and Urological Oncologist ADHB, CMDHB and 161 Gillies Ave, Epsom I am a member of the specialist group of the Prostate Cancer Workforce I am NZ Chairman of Training Board. I am a prostate cancer moderate. I believe we both undertreat and overtreatprostate cancer. What I ll Talk About Stages of Prostate Cancer Watchful Waiting Side Effects of Androgen Deprivation When to initiate Androgen Deprivation?? Available treatments for Prostate Cancer not responding to hormone treatment. Questions Localised Surgery Radiotherapy Locally Advanced Palliative Radiotherapy Selected case of Surgery and/or Radiotherapy with Curative intent Hormonal Therapy Metastatic Hormonal therapy Chemotherapy Palliative Radiotherapy No defined role for surgery When PSA increases despite hormonal therapy disease is termed castrate resistant. Castrate Resistant prostate develops only in a subset of patients. However has a 1% mortality. What is Watchful Waiting What is Active Surveillance? The expectant management of prostate cancer in patients who are not candidates for treatment with curative intent. Not offered surgery or radiation therapy. We are not giving up on patients but realising our treatment is worse than the disease. Life expectancy usually less than 1 years. The active treatment of patients with low risk prostate cancer who may require intervention in the future. A curative approach. Approx. 4% progress to radical treatment. Involves repeat PSA, Biopsy, Examination +/- MRI. 1

2 Why do we do watchful waiting? Mr P 76 years old 1 Gleason 7 prostate cancer PSA % Actuarial expected survival 87.3 years Therefore life expectancy is 11.3 years % Surviving Overall Survival Disease Free Survival No data exists for purely hormone treated prostate cancer. Post Radiation with recurrence of prostate cancer expected survival 13 years Time (Months) year old with Prostate Cancer Life expectancy is 81.2 years years remaining 7 Lower Morbidity 9-1 More likely to be 8 offered surgery with fewer long term effects. 9-1 Why not just start these Watchful Waiting patients on hormonal therapy? Bone Health There is no evidence that early hormonal therapy makes any difference to long term survival Quality of Life is reduced with ADT. ADT has associated medical risks with it. ADT leads to a 5% increased risk of fracture. Calcium and Vit D should be considered. In those who have access to insurance. Zoledronic Acid has been shown to reduce risk of fracture in prostate cancer. No evidence for alendronate. 2

3 Cardiovascular Health ADT accelerates cardiac disease. Associated with Impairment of lipid profile Increased LDL and reduced HDL Insulin resistance is 4% more common. 1% annual sudden cardiac death risk. These patients are at high risk and therefore should be have a cardiac risk work up. How long can we wait? Indications for Hormonal Therapy No-one knows Probably longer than we think. Varies from Urologist to Urologist. Absolute Metastatic disease Local symptoms. Ureteric Obstruction Lymphoedema Relative PSA cut off 2-5, no real evidence PSA doubling time <12 months. Selenium In Prostate Cancer The Old Paradign Long marketed as a cure for prostate cancer. Over 1, patients Level 1 evidence for lack of efficacy Now Level 1 evidence for harm. 91% increased risk of developing high grade prostate cancer. Patients should not be on Selenium or Vit E for prostate cancer prevention. Metastatic Prostate Cancer Hormone Resistance (12 months) Mitoxantrone/Prednisone (3 months) Total life expectancy (15 months) 3

4 New Paradigm Stop Press --- Chemotherapy before Hormones?? Sipuleucel T Hormone Resistance (12 months) Sipuleucel vaccine (4 months) (6 months) Enzalutamide(8 months) Docetaxol chemotherapy (circa 6 months) Mitoxantrone/prednisone (circa 3 months) Cabazitaxel (4 months) Total including non available treatments (44 months) 4 months survival, no subjective changes. Circa $15, Sipuleucel T (Zytiga) Traditional theory of prostate cancer treatment is that the cancer stops responding to testosterone. Reality is it just gets less sensitive Causes adrenal suppression Sli de 21 Radiographic Progression Free Survival based on 2 nd Interim Analysis Time to Opiate Use Data cutoff 2/12/211 Investigator Review Ryan et al. N Engl J Med 213; 368(2): Data cut off 2/12/211 Ryan et al. N Engl J Med 213; 368(2):

5 Time to Initiation of Chemotherapy Survival Improved by 5 months 1 (median, mos): 35.3 Subjects Without Death (%) Prednisone (median, mos): 3.1 HR (95% CI):.79 ( ) pvalue a : Prednisone Months From Randomization Prednisone Data cut off 2/12/211 Ryan et al. N Engl J Med 213; 368(2): Side Effects (n = 542) % Prednisone (n = 54) % Where do we sit in NZ Adverse event All grades Grades 3/4 All grades Grades 3/4 Fatigue Fluid retention Hypokalemia Hypertension Hyperglycemia Weight gain 5 7 Cardiac disorders ALT increased AST increased Sipeleucel T Never Low Priority from Pharmac Approx $2 per month Enzalutamide Available but not funded Approx $2/month IA3 data. Indications for Hormonal Therapy My Key points Absolute Metastatic disease Local symptoms. Ureteric Obstruction Lymphoedema Relative PSA cut off 2-5, no real evidence PSA doubling time <12 months. Watchful waiting is a reasonable approach in patients with <1-15 year life expectancy. Treat your patients on ADT as high risk cardiac patients. Most urologists will give a guideline for PSA trigger for re-referral but PSA >2 is reasonable to initiate review. If a PSA is flying up, rule out infection, repeat it and then be concerned if it is still doubling in less than 1 year. 5

6 Questions? 6