Week 3 - K - BPH and Prostatic Carcinoma (+Treatment) Flashcards
What is the approximate weight of the prostate gland in a young male adult?
20g
What type of epithelium covers the prostatic urethra?
Transitional cell epithelium covers the prostatic urethra
What forms the ejaculatory ducts and where does the ejaculatory ducts exit?
Formed by the seminal vesicle ducts joining with the vas deferens to form the ejaculatory duct
Exits into the prostatic urethra
What is the elevation of urothelium at the porstatic urethra where the ejaculotry duct enters and the prostatic ducts secrete into known as?
This is the verumontanum
What is the function of the fluid secreted through the prostate ducts of the prostate gland?
It secretes fluid that nourishes and protects sperm
The prostate gland has different zones What is the main zone that gives rise to benign prostatic hyperpasia (BPH)?
Ths is the transitional (peri-urethral transitional zone) zone
Why is it that in BPH there is an associated haemturia?
Because the hyperplasia grows so close to the urethra, this can put pressure on both the bladder and urethra leading to haematuria
Cone shaped region that surround the ejaculatory ducts What zone of the prostate gand is this?
This is the central zone
What is the region accounting for 70% of rise to malignant prostate carcinomas?
This is the peripheral zone
Prostate cancers are usually adenocarcinomas Which part contains the majority of glandular tissue? How much cancer arises from each area?
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
What is the most common malignancy affecting men in the UK?
Prostate carcinoma
What agegroup do 85% of prostate cancers affect?
85% of prostate cancers affect those aged 65+
What race is more at risk of prostate cancers? What gene mutation is seen to increase risk also? (seen in breast cancer)
Afrocarribean men
Mutation in BRCA2 gene also increaset he risk
Is BPH or prostatic carcinoma a more androgen or oestorgen driven process?
BPH is a more oestrogen driven process
Prostatic carcinoma is a more androgen driven process
Gross majority of prostate cancers are asymptomatic and are picked up by What two screening tests?
Picked up by digital rectal examination and by measuring the levels of prostate specific antigen (PSA)
Is prostate specific antigen or digital rectal examintion carried out first?
Carry out PSA before DRE as this can increase the levels of PSA causing a false positive
What are symptoms of porstate cancer malignancy?
Haematuria, haematospermia
Weight loss and bone pain
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?
Benign - smooth, can be asymmetrical enlargment
Malignant - usually asymmetrical and nodular masses on digital rectal examination
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?
DRE - digital rectal examinaiton
BPH
Prostatitis
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?
High semen levels and low serum levels
In prostatic carcinoma the serum levels increase
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?
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
What are some potential complications of TRUS?
Haemturia and haematospermia 0.5% risk of sepsis and rectal bleeding
What lobe of the prostate is common for prostatic hyperplasia and what for prostatic carcinoma?
Prostatic hyperplasia - this is usually median lobe
Prostatic carcinoma - posterior lobe (contains the peripheral zone)
The fibromuscular stroma is anterior lobe
The majority of prostate cancers (>95%) are multifocal adenocarcinomas What are the regional nodes for prostatic drainage and therefore carcinoma?
The iliac nodes
The most common sites for metastatic deposits include pelvic lymph nodes and the skeleton What are the characterisits lesions of prostatic metastases?
Have sclerotic lesions on bone instead of osteolytic
How does the osteosclerotic bone lesions from prostate cancer present?
usually lumbosacral so lower back pain
What is a very good predictor of prognosis of prostate cancer and is therefore widely used?
Gleason system which gives a score base on the architectural appearance of the prostate glands rather than the cytological features
The gleasons grading system give a score between 2 to 10 What does an increase in the gleason score show?
It increases with the losss of glandular structure and the replacement of disorganized malignant growth pattern
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?
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
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?
CT staging and bone scanning for metastases
T1-2 N0 M0
T3-4 N0 M0
What do these show in prostate cancer?
T1-2 N0 M0 - tumour confined to organ (prostate)
T3-4 N0 M0 - tumour spread to local adjacent structures
What on the TNM scale shows metastatic disease?
N+ or M+ shows metastases
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+)
Watchful waiting / active surveillance
Asymptomatic patients with well and moderately differentiated tumours and a life expectancy < 10 years.
What is the treatment option 1 performed for localised disease to the prostate? curative option
Radical prostectomy - removes the prostate to prevent metastases
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?
Radical radiotherapy + neo-adjuvant hormone therapy (androgen deprivation therapy)
Hormonal therapy is for symptomatic patients who need palliation (unfit for curative treatment) in prostatic cancer What are the options here?
Anti-androgen therapy - usually first line or LHRH (Luteinisng hormone releasing hormone) (aka GnRH (gonadotrophin releasing hormone) agonist
Name an anti-androgen drug? (steroidal and non-steroidal)
Bicalutamide -non steroidal anti-antrogen
cyproterone acetate - steroidal anti-androgen
If prostate cells are deprived of androgenic stimulation, they undergo apoptosis (programmed cell death). How does giving LHRH agoists cause this?
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
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?
Cytotoxic chemotherapy - give doclatoxel
Bone metastases - can give radiotherapy
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?
Treat organ confirmed prostatic carcinoma with radical prostectomy
Bone metastases is treated with radiotherapy
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?
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
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?
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
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?
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
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?
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).
What is given in progressive BPH not responding to treatment?
Transurethral resection of the prostate (TURP)
