Post on 08-Mar-2018
Dr Alvin TanConsultant Medical Oncologist
Waikato District Health Board
12:15 - 12:25 Advanced Prostate Cancer Care
Take Home Message
• Lots of men with prostate cancer
• GPs are important in managing prostate cancer
• PSA screening is controversial
• Increasing number of treatment options available
• GPs can prescribe abiraterone
(But please continue to listen for the next 10 minutes)
Demographics in NZ
• 3000 men are diagnosed with prostate cancer each year
• Approximately 650 men die from this each year
• Maori men are more likely to die from prostate cancer, often presenting with advanced stage at diagnosis.
Male cancer registration rates, by site, 25+ years, Māori and non-Māori, 2010–12
Source: New Zealand Cancer Registry (NZCR), Ministry of Health
Male cancer mortality rates, by site, 25+ years, Māori and non-Māori, 2010–12
Source: New Zealand Cancer Registry (NZCR), Ministry of Health
Importance of GPs in prostate cancer management
• Localised prostate cancer – screening / initial referral / Active surveillance
• Post surgery / radiation follow-up - PSA monitoring
• If recurrent/progressive disease • Prescribing hormone therapy and monitoring response• Managing ADT side effects and patient well-being• Analgesia• Liaise with hospice• Referrals to Radiation Oncology for palliative radiation for bone pain
• (NEW) – when castrate resistant, GPs can now prescribe abiraterone in consultation with Urology/Oncology
PSA – what is it?
• Glycoprotein produced by the prostate gland, responsible for liquefying seminal fluid
• Usually present in small quantities in serum
• In 2009, GP’s performed an average of 74 PSA tests per year per clinician (BPAC source)
Prostate Cancer Screening
• BPAC recommendations • Patient has right to decide
• Risk of overtreatment
• Risk of false positive / false negatives
• Risk factors• Age >50
• African-American > Caucasian > Maori/PI > Asian
• Family History
Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and European Randomized Study of Screening for Prostate Cancer (ERSPC) joint analysis
When does Medical Oncology get involved?
• In as many as 10-50% of localised prostate cancer may progress and spread to the pelvic lymph nodes and bone
• Mainstay therapy at this stage usually involves androgen deprivation therapy • This can last for months to years
Androgen Deprivation Therapy
• Inhibitive – GnRH agonist• Goserelin (Zoladex)
• 3.6 mg Q1 monthly, 10.8 mg Q3 monthly depot
• Leuprorelin (Lucrin)• 3.75 mg Q1 monthly, 11.25 mg Q3monthly, 30 mg Q6 monthly depot
• Competitive• Antiandrogens (as lead in prior to androgen inhibition)
• Bicalutamide• Flutamide• Cyproterone
Androgen Deprivation Therapy – Common side effects• Erectile dysfunction
• Loss of libido
• Hot flushes
• Osteoporosis
• Loss of muscle tone
• Weight gain
• Mood swings
Prognosis
• Early advanced disease – potentially years on ADT therapy • Castrate resistance develops over a median span of 18-24 months following
initiation of ADT. • Historically once castrate-resistant, median survival of 1-2 years.
With new therapies, median survival now 2-3 years. • Prognosis is associated with a number of factors:
• Sites of disease (ie visceral, bone alone)• Performance status• ALP• Hb• PSA doubling time• Pain at baseline
Docetaxel chemotherapy – castrate resistant setting• Outpatient IV chemotherapy given every 2 or 3 weeks for each cycle
• Usually 24-30 weeks of treatment
• 50% reduction in PSA levels in about half of patients
• Improve pain symptoms in 1/3 patients
• Improves QOL in 1/4 patients
• Improve overall survival by 2 ½ months
• Common side effects:• Infection risks, peripheral neuropathy, nausea/vomiting, hair loss, diarrhoea, fatigue
Docetaxel chemotherapy – castrate sensitive setting• New trial results in last 2 years (STAMPEDE, E3805)
• Early use of docetaxel in metastatic prostate cancer
• 6 cycles of chemotherapy
• Improves overall survival by 14-17 months, particularly in large volume metastatic disease
Abiraterone – castrate resistant setting
• Novel hormonal therapy affecting the CYP17 pathway
• 1000 mg daily (4 tabs) on an empty stomach
• Prolongs survival (4 months gain), PSA response and delays progression
• Blocks testosterone formation
• But leads to increase in mineralcorticoid hormone production • HTN, fluid retention, electrolyte imbalance
• This is mitigated by taking daily prednisone 5 mg BD.
• GPs can now prescribe this, in discussion with Urologist / Oncologist
Side effects of Abiraterone
• Common (1 in 10)• Fatigue, fluid retention, low potassium, hypertension , diarrhoea, urine
infection
• Occasional (1-10 in 100)• Liver derangement, cardiac arrhythmias, mild myelosuppression, reflux
• Rare (<1 in 100)• Myalgia, muscle weakness, adrenocortical insufficieny
What to do if your patient is on Abiraterone?
• Monthly blood pressure checks
• Monthly UEs
• Monthly review for first 3 months, then can extend out to Q3 months
• Liver functions tests every 2 weeks for the first 3 months, then every month
• Ensure prednisone is taken daily with Abiraterone
• Would check PSA at baseline and at 3 months (PSA can continue to rise for up to 3 months initially). Thereafter, can be Q2-3 monthly.
Other Treatments
• Sipuleucil-T vaccine (US, $$$)
• Radium 223 (AUS, $$$)
• Cabazitaxel chemotherapy (private, $$$)
• Enzalutamide novel androgen receptor antagonist (patient access program)
• Low dose steroids
• Biphosphonate infusions
• Analgesia + Hospice input
• Palliative Radiotherapy for localised symptoms (eg bone pain)
Take Home Message
• Lots of men with prostate cancer
• GPs are important in managing prostate cancer
• PSA screening is controversial
• Increasing number of treatment options available
• GPs can prescribe abiraterone