Modern Screening and Treatment of Advanced Prostate Cancer John Tuckey

Modern Screening and Treatment of Advanced Prostate Cancer John Tuckey

Commonest male cancer - 2939 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

ERSPC 11yrs 25yrs (est) Mortality reduction (screened) 27% 29% Number needed to screen 930 262 Number needed to treat 33 9

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

US Taskforce European Study NZ Prostate Cancer Taskforce

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

Doctors should provide high quality information to 50-70 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)

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

refer if abnormal DRE 50-70 yrs PSA 4.0 ng/m l 71-75 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%

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 0.7-0.9 have a higher risk Diagnosis and Management of Prostate Cancer in New Zealand

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

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: 2104-11, 2011 EORTC Bolla M et al Lancet Oncol 11 (11): 1066-73, 2010

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

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

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

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

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

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: 2029 2013

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

metastatic hormone sensitive cancer NCI Study published 2 June 2014

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

Life expectancy 21-33 months with new agents Extra potential life expectancy 23 months

TAK 327 Improved pain PSA QOL Tannock IF et al N Engl J Med. 2004 ;351(15):1502-12.

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

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

De Bono JS et al N Engl J Med. 2011 ;364(21):1995-2005. 1195 patients 4 month benefit in OS and PFS,PSA

Ryan CJ et al N Engl J Med. 2013 ;368(2):138-148. 1088 patients 8 month benefit in PFS

8 month delay in initiation of chemo 5 month OS benefit Ryan CJ et al N Engl J Med. 2013 ;368(2):138-148.

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

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

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: 411-422

Interim analysis 5 month benefit in OS Scher HI et al, N Engl J Med 2012 ; 367 (13) 1187-1197

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

Interim analysis 3.6 month benefit in OS Parker C et al, N Engl J Med 2013 ; 369 (3) : 213-223

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

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