Prostate cancer

Question 1

Outline the risk factors for prostate cancer

Answer 1

Age is the strongest risk factor - mainly affects men who are over 50.
Race - higher incidence if black
Genetic - 2/3 fold increase in risk if 1st degree relative is affected.
Diet high in fat and red meat
Overweight

Question 2

Where is the prostate located?

Answer 2

Lies below the bladder neck, anterior to rectum, traversed by urehtra

Question 3

Why is the treatment of prostate cancer difficult?

Answer 3

Lies near many importat structures

Question 4

Where does prostate cancer commonly metastasise to?

Answer 4

Bones

Question 5

How are prostate tumors graded?

Answer 5

Either TNM system of Gleason system

Question 6

What is the Gleason grading system?

Answer 6

Scoring based on what the tumor looks like under a microscope - how well differentiated it is. The more differentiated the better the prognosis.
A score of 2-4 is good, 5-7 moderate and 8-10 poor.

Question 7

Outline the clinical presentation of prostate cancer

Answer 7

Lower urinary tract symptoms - hesitancy, post-micturition dribbling, decreased void pressure, frequency, urgency, and nocturia.

If locally invasive - perineal pain, impotence incontinence, haematospermia.

Question 8

How can prostate cancer be diagnosed?

Answer 8

Digital rectal examination (PR) - cannot detect T1 at this stage.
PSA levels in the body
Transurethral ultrasound (TRUS)
CT/MRI scan to detect bone metastases.

Question 9

What is PSA?

Answer 9

Prostate specific antigen - glyccoprotein secreted by prostatic cells to aid liquidfication of semen.

Question 10

What are the normal levels of PSA?

Answer 10

0-4ng/ml

Question 11

Why are PSA levels often increased in prostate cancer?

Answer 11

PSA leaks through cancer cell membrane and into circulation.

Question 12

Is PSA a good diagnostic test? what else could it be used for?

Answer 12

OK - however up to 20% of men with prostate cancer will not have raised levels and can also be raised for other regions e.g. age, BPH.

PSA can also be used to monitor patients response to treatments.

Question 13

What kind of surgery is used to treat prostate cancer? When would surgery be appropriate?

Answer 13

Radical prostaectomy - involves removal of the prostate, seminal vesicles and sometimes pelvic lymph nodes.
Only perfomed in patients with stage 1 or 2 dises and who have at least a 10 year life expectancy.

Question 14

What are the complications associated with radical prostatectomy?

Answer 14

Can result in significant moribidity - impotence in (30-70%), incontinence

Question 15

When is radiotherapy used to treat prostate cancer?

Answer 15

Carried out in patients who are not suitable for surgery but have good life expectancy and localised disease.

Also used for symptom control in advanced disease and bony metastases

Question 16

What is brachytherapy?

Answer 16

Delivers radioaction through implantation of needles containing radioactive pellets into prostate glands.

Used in combination with androgen deprivation therpay.

Question 17

When do we use hormonal therapies?

Answer 17

Used in locally advance and metastatic cancer

Question 18

What is the idea behind hormone therapies?

Answer 18

Hormonal therapies block androgen drive that sustains most prostate cancers.

Question 19

What is Goserelin? How does it work and how is it given?

Answer 19

LHRH analog - luteinising hormone-releasing hormone (leads to testosterone release).

Disrupts the normally pulsatile release of LHRH - initially there is an increase in LH and then this followed by a decrease in both LH and testosterone.

This initial rise in LH can cause a transient increase in tumor volume (called a tumor flare) which can worsen symptoms if not blocked. Therefore we have to give androgen blocking drug such as Bicalutamide for the first few weeks to mask this (until the receptors become desensitised)

Question 20

When we prescribe gosrelin why do we also need to give an androgen blocking drug (e.g. bicalutamide) for the first few weeks of treatment?

Answer 20

Causes an initial rise in LH can cause a transient increase in tumor volume (called a tumor flare) which can worsen symptoms if not blocked. Therefore we have to give androgen blocking drug such as Bicalutamide for the first few weeks to mask this (until the receptors become desensitized)

Question 21

How do androgen blockers work?

Answer 21

Compete with DHT (dihydrotesterone, its active metabolite)

Question 22

What is bicalutamide and goserelin?

Answer 22

Androgen blocking drugs

Question 23

What is abiraterone? when is it used?

Answer 23

Oral androgen inhibitor for metastatic prostate cancer - licensed 1st line where chemotherapy is not yet clinically indicated.

Inhibits androgen production from testes, adrenal gland and prostate tumor cells.

Question 24

What must also be prescribed with abiraterone?

Answer 24

Must be given a steroid (prednisolone 5mg BD) abriaterone is an irrversible inhibitor of CYP17A1, an enzyme responsible for androgen and cortisol production.

Question 25

What side effects are associated with abiraterone?

Answer 25

side effects are often due to the low cortisol levels - peripheral oedema, hypokalemia, hypertension, increased risk of UTI (reasons unknown), elevated LFTs (monitor every 2 weeks for first 3 months of treatment)

Question 26

What is enzalutamide? what is its MOA (3)?

Answer 26

Potent androgen receptor signalling inhibitor. Has three MOA:

1. inhibits binding of androgens to androgen receptors
2. Inhibits nuclear translocation of activated receptors
3. Inhibits the association of the activated andorgen receptor with DNA

Question 27

When is chemotherapy used to in prostate cancer?

Answer 27

Used in patients with metastatic disease which is refractory to hormone therapy/abiraterone/enzalutamide.

Question 28

What is the commonly used chemotherapeutic regimen used in prostate cancer?

Answer 28

Docetaxel IV and prednisolone PO

Given every 21 days for up to 10 cycles

Question 29

How does docetaxel work?

Answer 29

Disrupts microtubular network of cells during cell division so mitosis cannot occur (see MDT lectures)

Question 30

What pharmaceutical care issues are associated with docetaxel/prednisolone chemotherapeutic regimen?

Answer 30

Must check BSA and doses against protocol
Check FBC - neutrophils >1.5 and platelets >100
Ensure patients have taken premed - dexamethasone 8mg bd for 3 days before starting chemo
Check LFTs
Ensure antiemetics prescribed
Do not take both steroids at the same time

Question 31

What are the likely side effects of the docetaxel/prednisolone chemotherapy regimen?

Answer 31

Myalagia, fluid retention, bone marrow supression, severe alopecia (although not an issue in elderly men), hypersensitivity reactions (premed with dexamethasone to reduce this and fluid retention)