Week 3 - K - BPH and Prostatic Carcinoma (+Treatment)

Question 1

What is the approximate weight of the prostate gland in a young male adult?

Answer 1

20g

Question 2

What type of epithelium covers the prostatic urethra?

Answer 2

Transitional cell epithelium covers the prostatic urethra

Question 3

What forms the ejaculatory ducts and where does the ejaculatory ducts exit?

Answer 3

Formed by the seminal vesicle ducts joining with the vas deferens to form the ejaculatory duct

Exits into the prostatic urethra

Question 4

What is the elevation of urothelium at the porstatic urethra where the ejaculotry duct enters and the prostatic ducts secrete into known as?

Answer 4

This is the verumontanum

Question 5

What is the function of the fluid secreted through the prostate ducts of the prostate gland?

Answer 5

It secretes fluid that nourishes and protects sperm

Question 6

The prostate gland has different zones What is the main zone that gives rise to benign prostatic hyperpasia (BPH)?

Answer 6

Ths is the transitional (peri-urethral transitional zone) zone

Question 7

Why is it that in BPH there is an associated haemturia?

Answer 7

Because the hyperplasia grows so close to the urethra, this can put pressure on both the bladder and urethra leading to haematuria

Question 8

Cone shaped region that surround the ejaculatory ducts What zone of the prostate gand is this?

Answer 8

This is the central zone

Question 9

What is the region accounting for 70% of rise to malignant prostate carcinomas?

Answer 9

This is the peripheral zone

Question 10

Prostate cancers are usually adenocarcinomas Which part contains the majority of glandular tissue? How much cancer arises from each area?

Answer 10

Peripheral zone contains majority of prostatic glandular tissue - accounts for 70% of cancer

Transitional zone accounts for 20% of cancers

Central zone accounts for 1-5% of cancers

Question 11

What is the most common malignancy affecting men in the UK?

Answer 11

Prostate carcinoma

Question 12

What agegroup do 85% of prostate cancers affect?

Answer 12

85% of prostate cancers affect those aged 65+

Question 13

What race is more at risk of prostate cancers? What gene mutation is seen to increase risk also? (seen in breast cancer)

Answer 13

Afrocarribean men

Mutation in BRCA2 gene also increaset he risk

Question 14

Is BPH or prostatic carcinoma a more androgen or oestorgen driven process?

Answer 14

BPH is a more oestrogen driven process

Prostatic carcinoma is a more androgen driven process

Question 15

Gross majority of prostate cancers are asymptomatic and are picked up by What two screening tests?

Answer 15

Picked up by digital rectal examination and by measuring the levels of prostate specific antigen (PSA)

Question 16

Is prostate specific antigen or digital rectal examintion carried out first?

Answer 16

Carry out PSA before DRE as this can increase the levels of PSA causing a false positive

Question 17

What are symptoms of porstate cancer malignancy?

Answer 17

Haematuria, haematospermia

Weight loss and bone pain

Question 18

When feeling for protstatic hyperplasia, it is the peripheral zone that is being felt which is good since 70-75 % of prostate cancers arise in the peripheral zone What is felt in benign vs malignant enlargment?

Answer 18

Benign - smooth, can be asymmetrical enlargment

Malignant - usually asymmetrical and nodular masses on digital rectal examination

Question 19

Because measuring the PSA is very sensitive to prostatic cancers it is good however it is not very specific (only 40%) as other conditios can cause a rise Name 2 things that can cause a rise in PSA?

Answer 19

DRE - digital rectal examinaiton

BPH

Prostatitis

Question 20

PSA is a glycoprotein (kallikrein-like serine protease) enzyme produced by the secretory epithelial cells of the prostate gland. In a healthy male, what are semen and serum levels of PSA?

Answer 20

High semen levels and low serum levels

In prostatic carcinoma the serum levels increase

Question 21

Men with an abnormal DRE, an elevated PSA

• Previous biopsies showing PIN or ASAP
• Previous normal biopsies but rising PSA trends

What investgations do these indicate for?

Answer 21

Indicate for a TRUS prostate biopsy (trans rectal USS guided) - 10 biopsies are taken from the prostate gland USS probe passed through the rectum and prostate visualized in transverse and sagittal sections

Question 22

What are some potential complications of TRUS?

Answer 22

Haemturia and haematospermia 0.5% risk of sepsis and rectal bleeding

Question 23

What lobe of the prostate is common for prostatic hyperplasia and what for prostatic carcinoma?

Answer 23

Prostatic hyperplasia - this is usually median lobe

Prostatic carcinoma - posterior lobe (contains the peripheral zone)

The fibromuscular stroma is anterior lobe

Question 24

The majority of prostate cancers (>95%) are multifocal adenocarcinomas What are the regional nodes for prostatic drainage and therefore carcinoma?

Answer 24

The iliac nodes

Question 25

The most common sites for metastatic deposits include pelvic lymph nodes and the skeleton What are the characterisits lesions of prostatic metastases?

Answer 25

Have sclerotic lesions on bone instead of osteolytic

Question 26

How does the osteosclerotic bone lesions from prostate cancer present?

Answer 26

usually lumbosacral so lower back pain

Question 27

What is a very good predictor of prognosis of prostate cancer and is therefore widely used?

Answer 27

 Gleason system which gives a score base on the architectural appearance of the prostate glands rather than the cytological features

Question 28

The gleasons grading system give a score between 2 to 10 What does an increase in the gleason score show?

Answer 28

It increases with the losss of glandular structure and the replacement of disorganized malignant growth pattern

Question 29

The TNM staging of the porstate cancer is similar to other TNM staging N - 0 for no lymph node involvment 1 - for regional node involvement M – Distant Metastasis M0 N0 Distant Metastasis M1 Distant Metastasis

What are the 4 different aspects of the T stage of TNM staging?

Answer 29

T1 Clinically in-apparent tumour not palpable or visible by imaging

T2 Tumour confined within the prostate

T3 Tumour extends through the prostatic capsule

T4 Tumour fixed or invades adjacent structures other than seminal vesicles: bladder neck, external sphincter, rectum, levator muscles or pelvic wall

Question 30

Once the doctor has confirmed the TNM staging of the prostatic carcnioma, a treatment plan must be started Imaging modalities are required for the staging What imaging modalities are used for staging of spread and bone?

Answer 30

CT staging and bone scanning for metastases

Question 31

T1-2 N0 M0

T3-4 N0 M0

What do these show in prostate cancer?

Answer 31

T1-2 N0 M0 - tumour confined to organ (prostate)

T3-4 N0 M0 - tumour spread to local adjacent structures

Question 32

What on the TNM scale shows metastatic disease?

Answer 32

N+ or M+ shows metastases

Question 33

Number of treatment options available for prostatic carcinoma Treatment depends on whether the cancer is active or not
If not active, what is the treatment? (this is seen in older patient eg 85+)

Answer 33

Watchful waiting / active surveillance

Asymptomatic patients with well and moderately differentiated tumours and a life expectancy < 10 years.

Question 34

What is the treatment option 1 performed for localised disease to the prostate? curative option

Answer 34

Radical prostectomy - removes the prostate to prevent metastases

Question 35

Locally advanced disease still means TNM score of T1-2, N0,M0 What can be given for locally advanced disease which has spread to adjacent strucutres eg pelvic floor and bladder?

Answer 35

Radical radiotherapy + neo-adjuvant hormone therapy (androgen deprivation therapy)

Question 36

Hormonal therapy is for symptomatic patients who need palliation (unfit for curative treatment) in prostatic cancer What are the options here?

Answer 36

Anti-androgen therapy - usually first line or LHRH (Luteinisng hormone releasing hormone) (aka GnRH (gonadotrophin releasing hormone) agonist

Question 37

Name an anti-androgen drug? (steroidal and non-steroidal)

Answer 37

Bicalutamide -non steroidal anti-antrogen

cyproterone acetate - steroidal anti-androgen

Question 38

If prostate cells are deprived of androgenic stimulation, they undergo apoptosis (programmed cell death). How does giving LHRH agoists cause this?

Answer 38

GnRH (LHRH) agonists act as agonists of the GnRH receptor, the biological target of gonadotropin-releasing hormone (GnRH).

However, after the initial “flare” response, continued stimulation with GnRH agonists desensitizes the pituitary gland (by causing GnRH receptor downregulation) to GnRH.

Pituitary desensitization reduces the secretion of LH and FSH and thus induces a state of hypogonadotropic hypogonadism

Question 39

Metastatic disease has a complicated therapy where you can choose between androgen deprivation therapy aand chemotherapy What drug can be given for the cytotoxic cehmotherapy? What is given for bone metastases?

Answer 39

Cytotoxic chemotherapy - give doclatoxel

Bone metastases - can give radiotherapy

Question 40

So prostatic cancer that is local disease - the type confirmed to the organ is treated how? Type that has locally spread is treated with radiotherapy + anti-androgens Metastatic is treated with Androgen deprivation therapy + cytotoxic chemotherapy How is the bone metastases treated?

Answer 40

Treat organ confirmed prostatic carcinoma with radical prostectomy

Bone metastases is treated with radiotherapy

Question 41

BPH typically presents with lower urinary tract symptoms (LUTS), which may be categorised into: * voiding symptoms (obstructive) * storage symptoms (irritative) * complications What are the symptoms in each of these categories?

Answer 41

voiding symptoms (obstructive): weak or intermittent urinary flow, straining, hesitancy, terminal dribbling and incomplete emptying storage symptoms (irritative) urgency, frequency, urgency incontinence and nocturia ,
post-micturition: dribbling
complications: urinary tract infection, retention, obstructive uropathy

Question 42

What drugs are used for the 1st line treatment of BPH? State mechanism of action and side effects How long can it take to show symptoms improvement?

Answer 42

Alpha-1 antagonists e.g. tamsulosin, alfuzosin

* decrease smooth muscle tone (prostate and bladder)

* considered first-line, improve symptoms in around 70% of men

* can take up to 6-8 weeks to show symptom improvement

* adverse effects: dizziness, postural hypotension, dry mouth, depression

Question 43

What drugs are used for the 2nd line treatment of BPH? State mechanism of action and side effects How long can it take to show symptoms improvement?

Answer 43

5 alpha-reductase inhibitors e.g. finasteride

block the conversion of testosterone to dihydrotestosterone (DHT), which is known to induce BPH unlike alpha-1 antagonists causes a reduction in prostate volume and hence may slow disease progression. This however takes time and symptoms may not improve for 6 months. They may also decrease PSA concentrations by up to 50% adverse effects: erectile dysfunction, reduced libido, ejaculation problems, gynaecomastia

Question 44

If the man has a mixed picture with storage symptoms and voiding symptoms that persist after treatment with an alpha-blocker alone, what can be considered to be given?

Answer 44

If the man has a mixed picture with storage symptoms and voiding symptoms that persist after treatment with an alpha-blocker alone, consider adding an antimuscarinic (anticholinergic) drug.

Oxybutynin (immediate release), tolterodine (immediate release), Do not offer oxybutynin (immediate release) to frail older men due to the risk of impairment of daily functioning, chronic confusion, or acute delirium (less common).

Question 45

What is given in progressive BPH not responding to treatment?

Answer 45

Transurethral resection of the prostate (TURP)