CASE 4 - PROSTATE CANCER Flashcards
1
Q
What is the size of the prostate?
A
Walnut / Chestnut
2
Q
What is the function of the prostate?
A
Makes and stores seminal fluid. It secretes proteolytic enzymes into the semen, which act to break down clotting factors in the ejaculate.
Contains spermatozoa, which has the ability to fertilise the female ovum
3
Q
What zone/area of the prostate is the most commonly implicated in prostate cancer?
A
Peripheral zone
75-80% of prostate cancers occur here.
4
Q
Prostate cancer is the _nd most common cause of death in men
A
Prostate cancer is the 2nd most common cause of death in men
5
Q
Name 3 non-modifiable risk factors for prostate cancer
A
- AGE (>40 years)
- RACE (African > Caucasian > Asian)
- FAMILY HISTORY (1 primary relative doubles your risk)
6
Q
Why is screening important?
A
Localised (and curable) disease is ASYMPTOMATIC
7
Q
What is the most common site of prostate cancer metastasis? What are some symptoms of metastases?
A
Bone (especially the axial skeleton)
SYMPTOMS: bone pain, pathological fractures, spinal cord compression, weight loss
8
Q
What is Prostate-specific antigen (PSA)?
A
Protease that is produced by benign AND malignant cells of the prostate
9
Q
What is the value of a DRE?
A
Increases the predictive value of PSA
10
Q
Describe 4 considerations that must be made when performing a DRE.
A
- Communication: tell the patient why it’s important (e.g. it increases our ability to pick up prostate cancer)
- Consent: verbal and sustained
- Setting: ensure privacy!
- Explain findings to the patient
11
Q
When and why is a prostate MRI done?
A
Done before a biopsy: alerts to areas of suspicion and where to target in a biopsy
12
Q
What are the pros and cons of a trans-rectal vs. trans-perineal ultrasound-guided biopsy?
A
TRANS-RECTAL (TRUS):
- Can do it while the patient is awake (local anaesthesia)
- Is above the dentate line, and the mucosa there is relatively insensitive
- CONS: can’t sample certain areas, risk of infection since it’s moving through the rectum
TRANS-PERINEAL: passed through the skin between the scrotum and perineum
- Reduced infection risk
- Slightly improved sample
13
Q
How is prostate cancer GRADED?
A
GLEASON GRADE: histological grade based on cellular architecture
Grades 3-5 are the only ones reported (grade 5 is the worst)
Score is calculated based on the 2 most common grades.
14
Q
Why is assessment of localised disease pivotal to prostate cancer treatment?
A
If it has metastasized, it is no longer treatable and management is centered around extending life
15
Q
Which investigations are used for the staging of prostate cancer?
A
- MRI - shows localised and advanced disease
- PMSA-PET CT: a prostate-specific marker is injected and allows you to see which cells contain prostate-specific membrane antigen
- WBBS (whole-body bone scan)
16
Q
Outline the factors affecting management of localised prostate cancer.
A
- PATIENT FACTORS: co-morbidities/life expectancy, surgical suitability, patient preference
- PATHOLOGY FACTORS: Gleason grade & radiological T stage
- PROSTATE FACTORS: may preclude some treatment options
- EQUIPMENT: availability, expertise
17
Q
The vast majority of men who have a small amount of low-risk prostate cancer will be fine. How should this be managed?
A
Focus on active surveillance. Any treatment will be overtreatment.
18
Q
How is prostate cancer STAGED?
A
TNM STAGING: look @ images
Stage 1 is unable to be felt
Stage 2 is the start of the pathological stage. It can be felt
Stage 3: cancer has spread from the prostate into nearby TISSUES
Stage 4: cancer has spread into nearby ORGANS (e.g. bladder, rectum) - no longer treatable
19
Q
A residual urine volume of more than ____mL may require further investigation.
A
A residual urine volume of more than 250 mL may require further investigation.
20
Q
How can flank pain indicate advanced prostate enlargement?
A
Hydronephrosis can present with flank pain
Hydronephrosis is caused by urinary stasis due to bladder outflow obstruction
21
Q
What is the normal volume of a prostate?
A
~20ccs.
22
Q
.
A
.
23
Q
Behavioural management of BPH
A
- Set times to go to the toilet
- Restrict evening fluid intake
- Avoid antihistamines and decongestants, which make urination more difficult
24
Q
Outline the conservative management of BPH
A
- Watchful waiting: in those with mildly symptomatic BPH, or as supplemental therapy
- Behavioural modifications: fluid restriction before bed, decreasing caffeine and alcohol intake
- Pharmacology: alpha-blockers and 5-alpha-reductase inhibitors (monotherapy, or combo therapy if Sx more severe)
25
What is the difference between Benign Prostatic Hyperplasia (BPH) and Benign Prostatic Syndrome(BPS)?
BPH = hyperplasia of the glandular and stromal cells of the transition zone of the prostate
BPS = lower urinary tract symptoms (LUTS) arising from BPH
26
What is PSA, what factors can cause it to be raised, and when is malignancy suspected?
Prostate-specific antigen is produced exclusively by the prostate and is responsible for liquifying semen
Can be raised by BPH, cancer, trauma, UTI, prostatitis
Malignancy is suspected when levels > 4ng/L
27
What's is TURP?
Transurethral resection of the prostate:
Most common surgical procedure for BPH (not bladder cancer).
It removes the part of the prostate which is blocking the urethra.
28
Give 3 examples each of irritative and obstructive symptoms of BPH.
IRRITATIVE Sx: urinary frequency, urgency, and urge incontinence, nocturia, dysuria
OBSTRUCTIVE: hesitancy, straining, poor/intermittent stream, prolonged terminal dribbling, sensation of incomplete voiding
Can be described together using the term LUTS
29
How common is BPH?
~50% of men >50 have BPH
30
What is the MOA of selective alpha-blockers? (First-line medication), e.g. doxazosin, tamsulosin
Blocks alpha-1 receptors, allowing smooth muscle relaxation in the bladder neck and prostate and decreasing resistance to urinary outflow.
Rapid response (<48 hours)
31
What is the MOA of 5-alpha-reductase inhibitors? e.g. finasteride
5-alpha reductase converts testosterone to DHT.
Inhibits 5‑alpha-reductase, which converts testosterone to dihydrotestosterone (a potent cellular androgen that stimulates prostate growth).
Reduces prostate size and improves symptoms and urinary flow rate.
32
What is the IPSS?
International Prostate Symptom Score: a scoring symptom based on the severity of BPH symptoms in the past 30 days.
Useful as a marker of disease progression and treatment response, in addition to marking candidates for surgery (e.g. if they're really bothered by Sx).
33
What causes the IRRITATIVE symptoms of prostate cancer?
Detrusor muscle overactivity - involuntary contractions during bladder filling
34
TRUE OR FALSE? BPH is not a risk factor for prostate cancer.
TRUE
35
Risk factors for BPH? (Modifiable and non-modifiable)
1. Race (African American)
2. Genetic susceptibility
3. Hormone levels
1. Obesity & metabolic syndrome
2. Low physical activity
3. Excessive alcohol consumption
36
Which investigations are used to diagnose BPH? Why?
Bladder ultrasound
Looks at post-void residual volume (PVR volume)
37
Initial investigations for BPH are mostly used to exclude more sinister causes of LUTS. Give 3 examples.
1. URINALYSIS: exclude haematuria, glycosuria, leukocytosis
2. eGRF: exclude kidney injury due to high-pressure bladder outflow obstruction
3. URINARY TRACT ULTRASOUND: assesses prostate volume, bladder wall, and exclude hydronephrosis
4. PSA: exclude prostate cancer (controversial)
38
Is a DRE recommended for people who do not have symptoms of prostate cancer?
NO
39
Does a negative DRE rule out prostate cancer?
NO - it could be too small to be felt.
40
Where is sperm formed?
Seminiferous tubules (look up a picture) of the testes
41
Where does the ejaculatory duct and urerthra join to create a common exit point for sperm and semen?
Prostate
| look at a sagittal view
42
What is a normal bladder volume?
500mL
43
What does 'BOO' stand for?
Bladder outlet obstruction
44
How long is the male urethra?
~20cm
45
A high-riding prostate on DRE can indicate what kind of pathology?
Rupture or injury of the membranous urethra: can cause bleeding which collects around the prostate and even the anterior abdominal wall.
Collecting blood in anterior abdominal wall --> pushes bladder up --> high-riding prostate
46
Why does cancer not affect the isthmus of the prostate?
It's the fibromuscular part - very little glandular tissue.
47
List the 3 sections of the male urethra
Prostatic
Membranous
Spongy
48
Label the zones and lobes of the prostate
.
49
Where do most prostate cancers occur, and where does BPH most commonly occur (in relation to the zones)?
CANCER: Peripheral/lateral zone (most of the glandular tissue is here)
BPH: Transitional zone/median lobe
50
List 2 possible side effects of prostatic biopsy
Rectal bleeding
Blood in semen
Blood in urine
51
What is the significance of peripheral zone prostate cancer in terms of invading adjacent structures and metastasis?
The proximity of the peripheral zone to the neurovascular bundle surrounding the prostate may facilitate spread into perineural and lymphatic pathways
52
Justin Bronson is a 54 yr old man who works as a fly-in fly-out (FIFO) worker in the oil industry and has returned to Adelaide from working on an oil rig off the Western Australian Coast for the last 3 months.
He has been having severe back pain for the last 2 months which keeps him awake at night. He has been feeling generally unwell for this time and has had to take leave from his job to seek treatment for his back pain.
He describes lumbar back pain for 2 months:
- present at rest
- worse with movement
- radiating down to his legs.
He also describes difficulty passing urine over the last 6 months with difficulty emptying his bladder.
WHAT IS THE RELEVANCE OF HIS BACK PAIN + OBSTRUCTIVE URINARY SYMPTOMS?
Bone pain indicates advanced/metastatic prostate cancer.
It is the most common site of metastasis (axial skeleton)
The back pain could also be related to hydronephrosis (another manifestation of prostate cancer), but this is less likely given that it radiates to his legs AND hydronephrosis is usually asymptomatic!!!
53
List 5 red flags for back pain
| FULIN
- Fever
- Unexplained weight loss
- Loss of feeling in legs
- Infection
- Neurologic deficits, e.g. Sx of cauda equina
54
List 3 differentials that could explain Mr. Bronson's back pain
1. Prostate cancer metastasis to the lumbosacral region causing radiculopathy (pinched nerve due to pressure from surrounding structures)
2. Disc herniation compressing the L5/S1 portion of the sciatic nerve
3. Osteoarthritis (?) due to occupation
4. MSK pain related to previous rugby injuries and occupation
55
Which physical exams would be good to perform on Mr. Bronson? Justify them.
1. PHYSICAL EXAM: DRE (prostate cancer)
2. LOWER LIMB NEUROLOGICAL EXAM: e.g. straight-leg raise, which can indicate disc herniation, look for other neurological deficits, UMNL vs. LMNL
56
Which INVESTIGATIONS would be good to perform on Mr. Bronson? Justify them.
1. PSA levels: >4g/L suggests malignancy
2. PROSTATE MRI: look for regions of interest prior to biopsy (but is expensive)
3. LFTs: raised Alk Phos indicates bone metastases (due to increased bone turnover)
4. PROSTATE BIOPSY: diagnositc
5. SPINAL X-RAY
6. ABDOMINAL US & CT/MRI: extraprostatic invasion, liver mets, urinary obstruction
57
What are NORMAL findings in a DRE?
| SNS, RP
- Smooth
- Nonfirm
- Symmetrical
- Roughly heart-shaped
- Painless
58
What are EARLY PROSTATE CANCER findings in a DRE?
| PLON
- Localised indurated nodules
- Otherwise smooth
- Nonfirm
- Painless
59
What are ADVANCED PROSTATE CANCER findings in a DRE?
| FAP
- Frank nodules
- Asymmetric areas
- Painless
60
List the 5 S signs that you look for on DRE.
Shape
Size
Surface (should be soft: becomes hard on malignancy)
Spread
Surrounds
61
Why does prostate cancer have a marked predilection for bone metastasis (especially to the pelvis and vertebral column)?
There is haematogenous spread --> invasion of elements of pelvic and venous plexus
The vertebral veins have no valves, giving an unobstructed pathway up the vertebral column
62
What is the treatment of prostate cancer dependent on?
1. Patient's age
2. Patient preferences
3. Medical condition
4. Life expectancy
63
What is the difference between watchful waiting and active surveillance?
Watchful waiting: less intense, you diagnose and then DON'T treat. Best when patients are elderly and have a slow-growing tumour OR other life-limiting comorbidities / <10-year life expectancy.
Active surveillance: regular follow-ups with cancer re-staging instead of treatment (PSA & biopsies). Treatment commences if the tumour progresses.
64
What type of lesion is produced by bone metastasis from prostate cancer?
Osteoblastic: bone deposition instead of destruction (which is osteolytic)
65
Describe the treatment for localised disease
1. Surgery: radical prostatectomy (removal of entire prostate gland, pelvic lymph nodes)
2. Radiation therapy: external-beam radiotherapy (EBRT) or brachytherapy (seeds) - not as easy to see that you've definitively gotten rid of all the cancer. Also harder for country patients to come in repeatedly
TREATMENT VARIES DEPENDING ON WHETHER IT'S LOCALISED OR LOCALLY-ADVANCED
66
What does external-beam radiotherapy involve?
36-40 fractions
CT imaging and multiple beam angles to focus dosage on prostate
67
What are the risks of radiation therapy?
| BUPE
- Bladder & bowel irritation leading to frequency & bleeding
- Urethral strictures
- Prostate swelling with treatment: urinary retention
- Erectile dysfunction
68
What is brachytherapy?
Radioactive seed insertion into the prostate (or whatever organ has cancer)
(dose depends on severity of cancer)
69
When can hormonal therapies be used in prostate cancer?
Hormonal-sensitive stages. Most prostate cancer is hormone-sensitive in the beginning.
After many months-years, it can become castrate (hormone) resistant
70
How is hormone-sensitive prostate cancer treated?
1. Achieve castrate levels of testosterone: GnRH agonist (ADT) or GnRH antagonist
2. Can combine w/ anti-androgen if patient experiences a flare reaction (due to LH rise, leading to too much testosterone)
71
When is PSA screening appropriate?
NOT at a population level: for individuals with risk factors (e.g. older age, FHx)
72
What are the side effects of androgen-deprivation therapy (ADT)?
(HELLO)
```
Hot flushes
Erectile dysfunction
Low libido
Loss of muscle mass
Osteoporosis
```
(basically similar to menopause)
73
Outline the physiology of GnRH and testosterone production.
Pulsatile GnRH causes testosterone rise.
You need fluctuating levels of GnRH in order for the anterior pituitary to produce LH and FSH --> stimulates testosterone production.
Subsequent testosterone production inhibits GnRH production.
74
What is the MOA of a GnRH agonist? e.g. gosrelin
Binds irreversibly to the pituitary gland, producing high levels of LH and FSH.
This then produces transiently high levels of testosterone, which negatively feeds back to the hypothalamus to stop GnRH production.
Takes ~ 7 days
75
What is the MOA of an androgen receptor antagonist? e.g. bicalutamide
What are its indications? (Name 2)
Competitively inhibits the binding of androgens to their receptors.
Binds to the pituitary gland and prevents GnRH from exerting its effect on the pituitary --> no FSH and LH --> no testosterone.
Takes ~ 3 days
INDICATIONS: reduce symptoms of testosterone flare (HELLO) and tumour flare
76
Outline the pharmacological management of prostate cancer (GnRH receptor antagonist, GnRH agonist, Anti-androgen)
Antiandrogen therapy can be used for androgen-sensitive, localised high-grade or metastatic prostate cancer
GnRH Agonist (e.g. goserelin) SC injection every 1-3 months: raises testosterone levels temporarily to induce negative feedback
Can be combined with an antiandrogen (e.g. bicalutamide) for complete androgen blockade. This is especially useful in the first 2-4 weeks to prevent flares caused by high testosterone levels.
https://www.youtube.com/watch?v=wZHjwsq5Css
77
At what PSA level are we actually worried
8-9
78
Why can prostate cancer be missed in a TURP?
Prostate cancer usually occurs in the peripheral zone, but TURP focuses on the area just around the prostate (transitional zone)
79
How is the Gleason score calculated?
The Gleason score is derived by adding together the numerical values for the two most prevalent differentiation patterns (a primary grade and a secondary grade).
As an example, if a biopsy consists of predominantly grade 3 and secondarily grade 4 disease, the combined score is "3+4" or 7. As more experience has been gained with Gleason grading, pathologists generally will not diagnose prostate cancer with composite Gleason scores of 2 to 5; thus, the range of composite Gleason scores on prostate biopsies is Gleason 6 to 10.
80
TUNA FISH for back pain red flags.
```
T = trauma
U = unexplained weight loss
N = Neurologic symptoms
A = Age > 50
```
```
F = fever
I = IVDU
S = Steroid use
H = Hx of cancer
```
81
GnRH antagonist
- Expensive
- Monthly injection
GnRH agonists come in 3 and 6-monthly injections
82
What are the side effects of selective alpha blockers?
- First-dose hypotension
- Orthostatic hypotension
- Dizziness
Precautions must be taken in patients w/volume depletion or patients on antihypertensives
83
What are the side effects of 5-alpha reductase inhibitors?
| DIG
- Decreased libido
- Impotence
- Gynaecomastia
84
How do antimuscarinics affect urinary function?
Antimuscarinics decrease PNS function.
Antimuscarinics block the actions of acetylcholine. Under PNS stimulation, the urinary bladder contracts to allow emptying. Voiding of the bladder is the result of PNS muscarinic receptor activation of the detrusor smooth muscle through the release of acetylcholine. Therefore, antimuscarinics will interfere with bladder emptying.
85
How does hypogonadotropic hypogonadism result from GnRH agonists (e.g. goserelin)?
GnRH agonist binds to receptors in the anterior pituitary and stimulates them to produce FSH and LH, which then causes a surge in testosterone.
Over time, continuous stimulation of the GnRH receptors in the anterior pituitary become desensitised to the hormone and stop producing FSH and LH.
https://www.youtube.com/watch?v=wZHjwsq5Css
86
What are the symptoms of hypogonadotropic hypogonadism?
- Hot flashes
- Loss of body hair
- Muscle loss
- Gynaecomastia
- Erectile dysfunction
- Osteoporosis
- Low libido
- Difficulty concentrating
87
Initially, treatment with GnRH agonists can cause temporary worsening of prostate cancer symptoms. Why is this?
Large spike in LH and FSH causes increased testosterone release.
Consequences are: tumour growth, urinary compression, spinal cord compression
