CANCER- PROSTATE CANCER Flashcards
What are the risk factors of prostate cancer?
AGE (strongest risk factor)
Race
Genetic: 2-3 fold increased risk if a 1st degree relative affected
Androgens
Diet that’s high in fat and red meat
What may protect males from prostate cancer??
Frequent ejaculation
Diet high in lycopenes (tomatoes!!)
Prostate cancers start out as adenocarcinomas. What is an ADENOCARCINOMA? Also seen in other cancers such as breast cancer.
A type of tumour that has a GLANDULAR origin.
This is why we see it in cancers such as breast cancer (this has glands) oesophageal cancer (glands in neck) and prostate cancer (due to prostate gland)
So in prostate cancer it starts in the prostate gland then can metastasise to the bones
Where does prostate cancer usually metastasise to??
The bones
What is grading of prostate cancer based on?
TNM staging
Of Gleason score
What are the symptoms of prostate cancer?
Hesitancy to wee
Post urination dribbling
Increased Frequency
Increased urgency
Nocturia (weeing in the night)
How common is prostate cancer?
It’s the most common cancer in men
Only 32% of all cases actually get diagnosed! men can actually die with it without knowing, the disease can either lay dormant or be very aggressive.
What are the metastatic symptoms of prostate cancer (i.e. if it has metastasised to the bones and lymph nodes)?
Bone pain Hypercalceamia Spinal cord compression sciatica (pain in the sciatica nerve in the leg) Fracture Lymphoedema (swollen lymph nodes)
How can we diagnose prostate cancer?
Digital rectal examination- examiner feels inside rectum for the prostate. Gives us an idea of the size of the prostate, its firmness (how hard it is) and any nodules. Not a very accurate test
PSA level (prostate specific antigen)
Transurethral ultrasound (more accurate than a digital rectal exam, but overall accuracy for cancer detection is low)
CT/ MRI scan- to look for metastases sites
Radio labelled bone scanning: sensitive and specific to detect bone metastases
What is PSA and what can it tell us?
Prostate specific antigen. It is a glycoprotein secreted by prostatic cells to aid the Liquification of semen.
PSA leaks through cancer cell membrane into the circulation!
So with prostate cancer we will see increased PSA levels
How accurate is a PSA level test?
Fairly accurate but Up to 20% of men with prostate cancer will not have raised PSA levels
PSA can also be used to monitor patients before and after treatment to assess their response!! If their PSA level is coming down it means they are responding to cancer treatment :)
one of the treatment options for prostate cancer is “watchful waiting”. What is this?
Used for well-differentiated localised cancer in patients who are elderly who have under 10 years life expectancy or significant co morbidities that may be affected by treatment.
Involves observation and PSA level monitoring but not treatment.
Its basically just leaving the cancer alone as they will probably die of something else before the cancer kills them. Only treat if the cancer progresses.
When is surgery used in the treatment of prostate cancer?
Used for patients with T1 or T2 disease who have at least a 10 YEAR LIFE EXPECTANCY
Surgery for prostate cancer involves a Radical Prostatectomy. what is this?
Removal of the prostate and sometimes the pelvic lymph nodes.
good prognosis: 85% disease free survival at 10 years!!
When is radiation given to prostate cancer patients?
For patients who are not suitable for surgery but had a GOOD LIFE EXPECTANCY and localised disease (not metastasised)
Can also be used as symptom control in advanced disease and bony metastasis
What are the side effects of Radical Prostatectomy (the surgery done in prostate cancer)?
Erectile dysfunction
Incontinence
(can also happen with the radiation treatment but this is less common)
Brachytherapy is used as a primary therapy or in combo with radiotherapy. What is BRACHYTHERAPY?
Radioactive pellets are implanted into the prostate gland
The pellets emit a low dose of radiation over several weeks/ months
Quite uncomfortable procedure to get these in so patients need anaesthesia
When are hormonal therapies used in Prostate cancer?
Used for locally advanced and metastatic cancer
What is the role of androgens in Prostate cancer?
Androgens: Testosterone produced in testes, androgens produced in adrenal glands
These are metabolised to DHT which is an active metabolite that can stimulate prostate cancer to grow.
Hormone therapies can block the androgen drive that sustains most prostate cancers.
How do hormonal therapies work?
They BLOCK THE ANDROGEN DRIVE that sustains prostate cancers.
Can use LHRH analogues. LHRH is Luteinizing Hormone Release Hormone: stimulates the release of LH which in turn controls the release of testosterone from the testes.
LHRH is released in a pulsatile manner and has a short half life. This means that LHRH receptors will become desensitised if they are permanently occupied.
So we can use LHRH analogues to permanently occupy and desensitise receptors and cause less testosterone to be released from the testes. Less androgens= cancer shrinks
Can you think of an example of an LHRH analogue??
Goserelin
Triptorelin
Initially increases LH release and then decreases LH and therefore testosterone, due to desensitisation of the LHRH receptors.
Hormonal therapies such as Goserelin (an LHRH analogue) can cause an initial increase in LH release. What can this cause?
The initial Increase in LH can cause and initial increase in tumour size “tumour flare”
This can worsen symptoms if its not blocked
Therefore Androgen blocking drugs (e.g. Bicalutamide and cytoperone) can be given for the first few weeks or continued after Goserelin finished.
What is a Bilateral Orchidectomy?
Removal of the testicle
Stops androgens (testosterone) being produced
Stops cancer growth
although its not a popular option!!
Can you think of any Androgen blockers (anti androgen drugs)?
Bicalutamide
Cyproterone
These work by competing with DHT (active metabolite that stimulates cancer growth) at receptor level. So there are no active metabolites to stimulate cancer cell growth!
How can we achieve maximum Androgen blockage?
Use a COMBINATION of LHRH analogues and anti androgen drugs.
But no definite proven benefit been shown yet
What are the side effects of hormonal therapies?
Erectile dysfunction Loss of Libido (sex drive) Gynaecomastia (men grow breasts) Breast tenderness Hot flushes Depression/mood changes Fatigue
So its like the menopause for men!!
When is chemotherapy indicated in prostate cancer?
When it has metastasised
When there is no response to hormonal therapy
usually Old men with this type of cancer so chemotherapy not really looked to that often
What are the two common chemotherapy drug combinations to use in prostate cancer?
Docetaxel and Prednisolone
Mixtoxantrone and Prednisolone
How does Docetaxel work??
Its a taxol- we saw it with Threadgill: bind to taxol-binding sites on the inside surface of microtubules.
It disrupts micro-tubular network of cells during cell division
Mitosis can no longer occur
Cell death
It is NICE approved for ‘Hormone refractory metastatic prostate cancer’
What are the side effects of the Docetaxel and Prednisolone chemotherapy combo?
Bone marrow suppression
SEVERE alopecia
Nausea and Vomitting (but Low emetogenicity)
Potentially:
Myalgia (muscle pain)
Fluid retention
Hypersensitivity
Can Take Pre-medication Dexamethasone before starting chemo to reduce Myalgia and Fluid retention
What should patients due to start docetaxel & prednisolone chemotherapy take 3 days before starting?
Dexamethasone (a steroid)
Can lessen some of the side effects
Ensure the patient knows when to take this: 3 days before starting!
What should you check before initiating docetaxel & prednisolone chemotherapy?
Check BSA (body surface area) and dose against protocol
Check FBC
Neutrophils should be over 1.5, platelets should be over 100 before starting each course!
Check LFTs:
need to decrease Docetaxel dose if Liver function is impaired
What should be done for nausea and vomitting with docetaxel and prednisolone chemotherapy?
This chemo regimen is mildly emetogenic
But with any mildly emetogenic or moderate emetogenic chemo, ANTIEMETICS should be prescribed.
E.g. Metochlopramide or domperidone
ABIRATERONE is a new oral androgen inhibitor used in prostate cancer. What sources of androgen production can it inhibit?
Androgen production from:
the TESTES
Adrenal gland
Prostate tumour cells
So Abiraterone blocks ALL 3 SOURCES of androgen in the body
Abiraterone prolongs overall survival by 3-4 months in patients who have had chemotherapy. (Now licensed to be used before chemo!)
It slows the cancer down but doesn’t CURE
It improves Quality of Life
Also gives good reduction in pain
What are the SIDE EFFECTS of Abiraterone??
Peripheral Oedema (swollen ankles, hands and feet)
Hypokalaemia
Hypertension
UTI’s
Elevated LFT’s: need to monitor every 2 weeks
How does the NEW drug ENZALUTAMIDE work?
Its an androgen receptor signalling inhibitor (remember androgen signalling is what DRIVES prostate cancer cell growth)
It blocks several steps in the androgen receptor signalling pathway
It inhibits signalling through Blocking androgen receptors (stopping androgen binding), inhibiting nuclear translocation of activated receptors, and inhibiting the association of the activated androgen receptor with DNA
When is Enzalutamide licensed?
Licensed for treating metastatic prostate cancer where the disease has progressed after DOCETAXEL chemotherapy.
What are the side effects of Enzalutamide?
Headache Hot flush Memory problems Visual hallucinations Risk of seizures (so be careful in epileptics!!) [Slightly strange side effects!]
Hormon therapy plays a large part in Prostate cancer treatment but many patients eventually become resistant
Chemotherapy is used in metastatic prostate cancer in palliative stages (end stages of life)- more for relief of symptoms
Newer drugs Abiraterone and enzalutamide can be used if patient is deemed fit for further treatment following the chemo.
