Vicki L3 - Prostate Flashcards
Prostate cancer is the ____ common cancer in men. Men have a __% lifetime risk of developing but only __% have clinically significant PC. Many have it but have no ____ and often just die of old age or something else.
Most
30%
10%
Symptoms
Risk factors:
- ___ = strongest risk factor
- Race = low incidence in ___ ____
- Genetics - 2/3 fold increase if __ ____ relative affected
- Androgens - rare in males castrated b4 puberty (______ plays a role)
- Protective factors = freq ____ and diet high in ______ (tomatoes)
Age Far east 1st degree Testosterone Ejaculation Lycopenes
Pathology and staging:
- Prostates normal function is to produce the ___ part of ____.
- It is an _______ and can metastasise to the _____.
- Grading is based on the ___ or ____ system.
Lower score =
____ differentiated
% likelihood progression by 10 yrs around 25%
% likelihood death by 15 yrs around 8%
Higher score =
_____ differentiated
% likelihood progression by 10 years around 70%
% likelihood death by 15 yrs around 65%
Fluid part of semen
Adenocarcinoma and can metastasise to the bones
TNM (tumour, nodes, metastases)
Gleason system
Well
Poorly
Clinical presentation:
- Lower urinary tract symptoms caused by localised prostate cancer (similar to symptoms caused by ___)
- 5 symptoms - what are they?
BPH
- Increased frequency
- Hesitancy
- Post micturition dribbling
- Nocturia
- Reduced void pressure
1/3 of patients present with symptoms from locally invasive or metastatic disease:
Locally invasive disease symptoms due to invasion of neural structures e.g ____ base and _____ tissues:
(4) symptoms - what are they?
Bladder base and perirectal tissues:
- impotence
- haematospermia
- perineal pain (adjacent to anus)
- incontinence
Metastatic symptoms result from ___ and ____ ____ involvement and have an effect on related structures: 6 symptoms. What are they?
Bone and Lymph node
- Bone pain
- Hypercalcaemia
- Spinal cord compression
- Sciatica/paraplegia
- Fracture
- Lymphoedema
Diagnosis:
1) ____ ____ examination - info on ___ of prostate, ____, ____.
Cannot detect T1 disease (nodules too small to feel) - can feel bigger ones though. The test is limited as the accuracy depends on the _____. Could also be ___.
2) ___ - prostate ____ _____. A glycoprotein secreted by prostatic cells to aid ______ of semen. Leaks through cancer cells membrane into circulation. ____ of over 50% is associated with ____ metastases.
Up to 20% of men with PC don’t have raised ___ levels and it also increases with ___ in general and benign prostate enlargement. Despite this, levels are still measured to monitor pts ____ and ___ therapy to assess response.
Digital rectal examination
Size of prostate, nodules and firmness
Examiner
BPH
PSA (prostate specific antigen)
Liquidification
PSA
Bony
PSA
Age
before
after
Diagnosis of PC:
1) ______ ultrasound (TRUS) - more accurate than PR exam for staging PC but overall cancer detection is low. An ______ probe is inserted into the ____ to image prostate and usually a ____ is performed at the same time
2) CT/___ scan - to identify _____ disease
3) _______ bone scanning - sensitive and specific way of detecting bony mets
Transurethral
Ultrasound
Rectum
Biopsy
CT/MRI scan to identify metastatic
Radiolabelled
4) Brachytherapy
Delivers _____ through implantation of needles containing radioactive pellets into ______ gland.
The pellets are usually left in _____ and emit low dose _____ over several weeks/months. Used at primary therapy in combination with radiotherapy or ______ deprivation therapy. Conducted under general/spinal anaesthesia. Efficacy and long term side effects similar to surgery/radiotherapy.
Radiation Prostate Permanently Radiation Androgen
5) Hormonal therapies
In locally advanced and metastatic PC. Can combine with ______ and radical prostatectomy in locally advanced disease.
Rapid response but duration only really lasts _ years. Hormone therapies block _____ that drive and sustain most PCs. Androgens consists mainly of _____ produced in the testes. 10% androgens are produced in the _____ _____. _____ and other androgens metabolised at cellular level to dihydro______ (DHT) which is an active metabolite. It is also the target for some of these treatments.
Radiotherapy 2 years Androgens Testosterone Adrenal gland Testosterone dihydrotestosterone
Production of androgens:
1) ______ = produced by testes and is in circulation
2) production is under control of __ released from pituitary gland
3) __ is under control of ____ released from hypothalamus
4) ____ released in pulsatile manner and ____Rs are desensitised if constant stimulation
5) Desensitisation is exploited in treatments
Testosterone LH LH LHRH LHRH LHRHRs
Hormonal therapies:
____ blockade is achieved in several ways.
1) Bilateral ________ = remove both ____ to stop _____ secretion
2) LHRH analogues (g____, t______) monthly/3 monthly sc depot injections. Disrupt normal pulsatile release of LHRH. The receptors think there’s loads of LHRH so increase __ production causing receptors to ______ resulting in decreased __ and _______ action. The initial increase in __ can cause transient increase in tumour size (_____) and worsen symptoms so an androgen blocker is often given for the first few ____ e.g. b_______
Androgen Orchiectomy Testicles Testosterone Goserelin and triptorelin LH desensitise LH Testosterone LH flare Bicalutamide
Androgen blockers e.g. ______ and cyproterone. Compete with ___ at receptor level within PC cells. Give for a few _____.
Bicalutamide
DHT
Weeks
Maximal androgen blockade. Combination of ____ analogue e.g. ______ and anti androgen e.g. ______.
LHRH
Goserlein
Bicalutamide
Intermittent hormone therapy: Treat with ____ analogue but withdrawal of this may allow growth of hormone sensitive cells in tumour which can be treated again as ___/_____ dictate. So give an injection and ___ levels should decrease then wait for ____ levels to increase again and then repeat. So treat in _____.
LHRH PSA/symptoms PSA PSA Cycles
Side effects of hormone therapies:
Due to decreased _____.
7 things. what are they?
- Loss of libido
- Impotence
- Gynacomastia
- Breast tenderness
- Fatigue
- Hot flushes
- Depression/mood changes
Metastatic prostate cancer:
New therapies: A______ - a CYP17A1 inhibitor. This enzyme is responsible for _____ and _____ production. This therapy is an oral _____ inhibitor for metastatic prostate cancer. It is licensed 1st line where ____ is not yet clinically indicated i.e. symptoms are mild or asymptomatic (WHO PS _ or _)
It is also licensed after failure of ______ therapy or _____therapy. It inhibits _____ production from testes, _____ _____ and prostate tumour cells. All 3 sources of ____ in the body.
Must give this with a ____ (e.g. _____ 5mg po od) as A_____ inhibits the production of _____ too. This decrease in ____ would lead to the hypothalamus increasing ACTH leading to symptoms of cortisol deficiency.
Symptoms include: (5) things what are they?
In chemo naive patients the time to needing chemo with this therapy is around 25 months vs around ___ months with placebo! Prolongs overall survival by around 3-4 months in its who had prior chemo. It also reduces ____ associated with the tumour.
Abiraterone Cortisol and androgen Androgen Chemotherapy 0 or 1 hormonal or chemotherapy Androgen adrenal gland Androgen Steroid e.g. prednisone Abiraterone Cortisol Cortisol
Hypertension, oedema, hypokalaemia, UTIs, elevated LFTs (monitor every 2 weeks for first 3 months treatment)
New therapies - E________
Potent _____ receptor signalling inhibitor - blocks several steps in ______ receptor signalling pathway.
Inhibits binding of ____ to ____ receptor and inhibits their nuclear _____. It also inhibits activated receptors association with ___. As with Abiraterone it is licensed in metastatic PC where ____ is not yet clinically indicated i.e patient is _______ or mildly _____ (WHO PS 0-1). Also licensed for treatment of metastatic PC where disease progressed on/after D_____ therapy.
Side effects (5) what are they?
For chemo naive patients time to needing chemo = 28months which _____ vs __._ months which placebo.
In patients with prior chemo the overall survival is 18.4 months on E______ compared to 13.6months with placebo.
54% patients get at least a 50% reduction in ___.
Enzalutamide Androgen Androgen Androgen to androgen receptor Translocation DNA Chemotherapy Asymptomatic or mildly symptomatic Docetaxel
Hot flushes, increased risk of seizures, visual hallucinations, headache, memory issues
Enzalutamide
10.8
Enzalutamide
PSA
Chemotherapy:
- Usually for _____ care in metastatic PC.
- In metastatic disease refractory to hormone therapy/a_____/e_______.
- Difficult group of patients as usually older with poorer ____ PS and often have co-_______.
- A common regime is: ______ and _____.
- ______ and _____ regimen:
- ______ IV infusion day 1 and _____ bd orally continuously
- Given every 21 days for up to __ cycles
- _____ disrupts micro tubular network of cells during cell division so ____ cannot occur and leads to cell death
- _____ used as inhibits _____ production from _____ glands
Side effects(6) what are they? What is given to help with 2 of the side effects?
Palliative Abiraterone/enzalutamide WHO PS Co-morbidities Docetaxel and prednisolone
Docetaxel and prednisolone
Docetaxel
Predisolone
10 cycles
Docetaxel Mitosis Prednisolone Androgen Adrenal
Severe alopecia Bone marrow suppression Nausea and vomiting Myalgia and arthralgia (achy joints/bones) Fluid retention Hypersensitivity
Dexamethasone for fluid retention and hypersensitivity. Given as a premed
What are the pharmaceutical care issues with the chemotherapy regimen _____ and _____ used to treat metastatic PC refractory to hormone therapy/abiraterone/enzalutamide?
- Check ____ and dose
- Check ___ and ______ equal to or above 1.5 and platelets above or equal to 100 before each course of chemo
- ensure patient has taken ______ premedication for _ days starting the day before therapy
- Check ___ and reduce _____ dose if impaired
- Ensure _____ for mild to mod emetogenic chemo is prescribed e.g. ________ or _______ 10mg tds prn.
- ensure patient understands when to take dexamethasone and prenisolone and that they are steroids so need a _____ _____.
Docetaxel and Prednisolone BSA and dose FBC and neutrophils Dexamethasone premedication for 3 days LFTs and reduce docetaxel Antiemetics Metoclopromide or domperidone 10mg tds prn Steroid card
