Modern Screening and Treatment of Advanced Prostate Cancer John Tuckey

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1 Modern Screening and Treatment of Advanced Prostate Cancer John Tuckey

2 Commonest male cancer per year Third male cancer death 670 per year More die with it than of it but More people die of prostate cancer than breast cancer

3 ERSPC 11yrs 25yrs (est) Mortality reduction (screened) 27% 29% Number needed to screen Number needed to treat 33 9

4 Screening makes small or no difference to prostate cancerspecific mortality and concerns exist for harm, some of which may be unnecessary - over-treatment of low risk patients - morbidity - screening morbidity -treatment injury No to population based screening

5 US Taskforce European Study NZ Prostate Cancer Taskforce

6 Shared decision making for PSA testing - provide high quality information - - individuals decide Quality improvement programme - MOH and PHO s

7 Doctors should provide high quality information to yr old men on prostate cancer and PSA testing For asymptomatic men concerned about prostate cancer or requesting PSA - harms and benefits of screening - quantitative visual data - informed consent - prostate care pathway (PHOs and MOH)

8 testing must include PSA and DRE PSA at least 3 days after ejaculation normal PSA is now < 4ng/ml

9 refer if abnormal DRE yrs PSA 4.0 ng/m l yrs PSA 10.0 ng/ml >76 yrs PSA 20.0 ng/ml Rapidly rising PSA useful numbers - PSA 4-10 the risk of cancer is 40% - PSA > 10 the risk of cancer is 67%

10 positive family history 1 first degree relative 2 x risk 2 first degree relatives 4-11 x risk risk stratification reasonable if PSA over upper quartile have a higher risk Diagnosis and Management of Prostate Cancer in New Zealand

11 locally advanced but curable disease incurable disease either due to - spread -age

12 What do we know? - combining external beam and antiandrogens increases survival over either therapy alone XRT + ADT 74% ADT 66% XRT + ADT 51% XRT 39% MRC UK PR07 EORTC MRC Warde P et al Lancet 378: , 2011 EORTC Bolla M et al Lancet Oncol 11 (11): , 2010

13 what do antiandrogens do? - anti-androgens delay the onset or progression of symptoms

14 watchful waiting observation of men with prostate cancer unsuitable for curative treatment to determine when to institute palliative hormonal therapy balancing side effects against risk of progression

15 Active surveillance a close monitoring programme of men with low risk prostate cancer, eligible for curative treatment, to detect disease progression so treatment can be started

16 hot flushes osteoporosis reduced muscle mass, fatigue increased cardiovascular risk cognitive and sexual function oral agents diarrhoea, liver dysfunction, gynaecomastia

17 Metastatic - LHRH or orchidectomy more efficacious than oral antiandrogens as first line therapy - total androgen blockade meta-analysis - 3% survival benefit but reduced QOL - 3% lower survival with cyproterone acetate Aronson N et al AHCPR 1999

18 Some have side effects with antiandrogens Intermittent vs Continuous antiandrogens - no difference in survival - intermittent improved general wellbeing physical activity sexual function Niraula et al J Clin Oncol 31:

19 when to institute treatment before symptoms begin absolute - metastatic disease - ureteric or outflow obstruction - lymphoedema relative - aggressive disease - PSA doubling time less than 12 months - PSA over 30

20 metastatic hormone sensitive cancer NCI Study published 2 June 2014

21 Metastatic Prostate Cancer - antiandrogens Castrate Resistance (12-18 months) Progression 6-12 months Mitoxantrone/Prednisone (3 months) Total life expectancy (21-33 months)

22 Life expectancy months with new agents Extra potential life expectancy 23 months

23 TAK 327 Improved pain PSA QOL Tannock IF et al N Engl J Med ;351(15):

24 Docetaxel - usually given when begin to have symptoms - responses can be dramatic - tolerability good tiredness, minor hair loss - funded by government - refer early

25 CYP17 inhibitor Cholesterol X X Testosterone Aldosterone Cortisol affects androgen production in adrenals, prostate cancer mineralocorticoid excess treated with an inhibitor

26 De Bono JS et al N Engl J Med ;364(21): patients 4 month benefit in OS and PFS,PSA

27 Ryan CJ et al N Engl J Med ;368(2): patients 8 month benefit in PFS

28 8 month delay in initiation of chemo 5 month OS benefit Ryan CJ et al N Engl J Med ;368(2):

29 side effects when is best? - minor GI - pre chemo 50% respond - post chemo 40% respond cost - $5k per month buy one get one free - similar drugs on trial

30 autologous immunotherapy - harvest antigen presenting cells - incubate with PAP GM CSF - place APC s back in patient - APC s activate T cells against prostate cancer cells

31 512 patients, 2;1 Sipuleucel-T vs placebo asymptomatic or minimally symptomatic minimal side effects median survival 25.8 vs 21.7 months Kantoff PW et al N Engl J Med 2010; 363:

32 Interim analysis 5 month benefit in OS Scher HI et al, N Engl J Med 2012 ; 367 (13)

33 well tolerated - little fatigue - gastrointestinal symptoms - avoid if history of seizure sourced from UK - $10K per month

34 Interim analysis 3.6 month benefit in OS Parker C et al, N Engl J Med 2013 ; 369 (3) :

35 less myelosuppression than strontium trial population only had bony not visceral metastases probably available at the end of the year

36 NZ Prostate Cancer Taskforce guidelines will be released later this year interactive computer-based guides will help inform and educate GP s as well as patients new agents have changed the paradigm for advanced prostate cancer they can improve QOL and survival refer early

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