Prostate Cancer Flashcards
What is the most common cancer in men?
Prostate cancer
Where does the prostate lie?
At base of bladder
What is the function of the prostate?
Produce prostatic fluid which mixes which sperm
What are the three zones of the prostate?
Central zone
Transitional zone - lies next to urethra
Peripheral zone - lies posterior
In which zone does BPH develop?
Central
Which zone is most commonly affected by prostate cancer?
Peripheral
Why is DRE important in detecting prostate cancer?
Can tell:
- if it is enlarged
- if it has nodules, is firm or asymmetric
What is the clinical T staging for prostate cancer?
T1: tumour on biopsy, DRE normal
T2: tumour palpable on DRE, not has not spread outside prostate
T2a: tumour if half or less of one lobe
T2b: tumour is more than half of 1 lobe, but not both
T2c: tumour is both lobes but within prostatic capsule
T3: tumour spread beyond prostatic capsule
T3a: tumour has spread through capsule on one or both sides
T3b: tumour has invaded 1 or both seminal vesicles
T4: tumour has invaded other nearby structures
What produces PSA?
Normal and cancerous prostate cells
What is the role of PSA?
Helps to liquefy seminal fluid to allow sperm to move from freely
Also dissolves cervical mucus
How can you measure PSA levels?
Serum levels
What must you remember about PSA levels?
Normal levels of PSA raise with age
What things may cause an increased serum PSA?
BPH Prostate cancer Prostatitis UTI Biopsy Catheterisation
What things may cause a decreased PSA?
Ejaculation
Prostatectomy
Hormonal therapy
How sensitive is PSA for prostate cancer?
Not very - hence the PSA threshold for investigation is quite low
How is the definitive diagnosis of prostate cancer made?
Biopsy
How is prostate biopsy performed?
Transrectally (under US guidance)
Occasionally trans-perineally if it is an anterior tumour
What grading system is used to grade prostate cancer?
Gleason (1-5)
What are gleason grades 1 + 2?
Very well differentiated and form glands similar to normal prostate tissue
Rarely tumours
What are gleason grades 3 + 4?
Cancer appears progressively less well differentiated
What is gleason grade 5?
Least differentiated
Sheets of malignant looking cells that do not form glands at all
Usually a mixture of gleason grades are seen on biopsy, so how does the pathologist decide what the gleason grade is?
Primary grade = most prevalent pattern
Secondary grade = second most prevalent pattern
Sum primary and secondary grades to get gleason score
What do the gleason scores represent?
Gleason <6 is not cancer
Gleason 6 = well, differentiated, non-aggressive tumour
Gleason 7 = moderately differentiated disease, moderately aggressive
Gleason 8, 9, 10 = highly aggressive tumour that is poorly differentiated
How does non-metastatic prostate cancer tend to present?
Lower urinary tract symptoms (LUTS)
What are the two types of LUTS?
Storage symptoms
Voiding symptoms
What are storage symptoms?
Urinary frequency Nocturia Urgency Urinary stress Urge incontinence
What are voiding symptoms?
Poor urinary flow Hesistancy Straining Intermittency Incomplete emptying
What investigations should men with LUTs have?
Urinalysis
Abdominal Ex
DRE
When should PSA be measured?
LUTS + abnormal prostate on DRE or patient concerned about prostate cancer
Name a good subjective and objective measure of a man’s urinary symptoms
Subjective: international prostate symptom score
Objective: uroflowmetry
How does uroflowmetry work?
Urination into flowmeter which measures the cumulative weight of urine with time –> ml/s rate
What is a generally acceptable uroflowmetry score?
> 15ml/sec
What is a generally unacceptable uroflowmetry score?
<10ml/sec
This suggests significant outflow obstruction
How might metastatic prostate cancer present?
Bone pain, pathological fracture
Spinal cord compression
Marrow failure (anaemia, bleeding, infections)
Constitutional symptoms of metastatic disease (e.g. anorexia, wt loss, fatigue, malaise)
Why do we not screen for prostate cancer?
It doesn’t decrease deaths from prostate cancer
Overdiagnosis of prostate cancers that were unlikely to affect the men
Most men with prostate cancer will die of something else before they die of prostate cancer
How can prostate cancer spread?
Direct invasion into prostatic capsule/seminal vesicles
Lymphatic spread to pelvis and para-aortic lymph nodes
Haematogenous spread to bones
What staging investigations are commonly used in prostate cancer?
MRI pelvis
Bone scan
CT chest and abdo sometimes
What things can be used to risk assess patients with prostate cancer?
T stage
Gleason score
PSA
What things would put someone in a high risk group for prostate cancer?
PSA >20 or Gleason score 8-10 or Clinical T stage T3A/B or T4
What things would put someone in an intermediate risk group for prostate cancer?
PSA 10-20 or Gleason score 7 or Clinical T stage T2B/C
What things would put someone in an low risk group for prostate cancer?
PSA <10 and Gleason score 6 and Clinical T stage T1 or T2A
What investigations are required for low risk patients with prostate cancer?
MRI prostate as risk of nodal and bony mets so low
What investigations are required for intermediate risk patients with prostate cancer?
MRI of pelvis and bone scan
What investigations are required for high risk patients with prostate cancer?
MRI pelvis, CT abdo and pelvis and bone scan
How does TNM staging work?
T - see as prev. flashcard
N - nodal involvement
N0 - no spread to regional lymph nodes, N1 - spread
M - mets - M0 - no mets, M1 - mets (M1a: cancer spread beyond regional nodes; M1b: cancer spread to bone, M1c: cancer spread to other sites)
Is metastatic prostate cancer curable?
No
What palliative treatments are available for prostate cancer?
Systemic - hormonal, chemo, biologics, bisphosphonates
Local/regional - radiotherapy/TURP for urinary symptoms
What drives most prostate cancers?
Circulating androgens, e.g. testosterone
Therefore reducing circulating testosterone is v. effective
What are the ways hormonal therapy can work?
- Reducing testicular production of testosterone (androgen deprivation therapy)
- Blocking testosterone effects at its receptor
- Reducing production of androgens from other sources
How can ADT be achieved?
Orchidectomy (surgical castration) GnRH agonists (chemical castration) GnRH antagonists (chemical castration)
How can you block testosterone effect at its receptor?
Anti-androgens, e.g. cyproterone acetate or bicalutamide
How can you reduce the production of testosterone from other sources?
Adrenal production of androgens can be downregulated with prednisolone
Autocrine production of androgens by prostate cancer cells can be reduced by steroid synthesis inhibitors
How long do prostate cancers remain hormone sensitive?
Usually about 18 months
What happens after the cancer progresses despite androgen deprivation?
It is labelled as castrate resistant prostate cancer
Median survival is 1-2 years
What does GnRH stimulate?
Anterior pituitary to produce LH and FSH
What does LH do in men?
Stimulates Leydig cells to make testosterone
What does FSH do in men?
Stimulates spermatogenesis
Give examples of GnRH agonists
Goserelin and triptorelin
How do GnRH agonists work?
Cause initial spike in LH before tonic stimulation at anterior pituitary leads to downregulation of LH
How do you prevent the LH spike at the initiation of GnRH agonist treatment being an issue?
Give anti-androgens for the first 2 weeks of treatment as flare can lead to rapid prostate cancer growth
How do GnRH antagonists work?
Cause rapid reduction in LH
Give an example of a GnRH agonist
Degarelix
What are the treatment options for men with localised prostate cancer?
Radical - prostectomy, radical radiotherapy, brachytherapy
Monitoring options - watchful waiting, active surveillance
Cryotherapy, HIFU
Palliative hormonal therapy, TURP or radiotherapy
What is active surveillance?
Monitoring with a view to radical therapy if the cancer progresses
What is watchful waiting?
Monitoring with a view to palliative therapy if the cancer becomes symptomatic
What is radical prostectomy?
Removal of the whole prostate gland, usually with seminal vesicles and pelvic lymph node dissection
What is TURP?
Not curative for prostate cancer
Involves coring out centre of prostate gland in order to improve urinary flow
How can radical prostectomy be performed?
Retropubically, perineal, laparoscopically
What additional treatments do patients receiving radical radiotherapy for prostate require in the three risk groups?
Low - none
Intermediate - 6m hormonal therapy prior
High - 24-39 hormonal therapy
What is a major CI for brachytherapy?
Obstructive symptoms as brachytherapy causes significant swelling of the prostate gland
Others: IPSS >10 Qmax <10 Prior TURP Prostate volume >50ml
Who should be considered for active surveillance?
Those with low risk prostate cancer that is unlikely to act aggressively
What may be involved in active surveillance?
3 monthly visit for DRE and PSA
Repeat biopsies after 1 year, 4 years and 7 years
What may be indications for coming off of active surveillance?
Patient preference to get radical therapy
Steadily rising PSA
Increase in gleason score 7 or more
Who is watchful waiting for?
Patients with localised disease where radical treatment would be inappropriate and who wish to delay palliative treatment until symptoms develop
What does watchful waiting involve?
No active monitoring but if they develop symptoms they must inform their GP
What are the pros and cons of radical prostectomy?
Cons - Risk of erectile dysfunction, urinary incontinence
Major surgery
Pros - improves obstructive symptoms
What are the pros and cons of radical radiotherapy?
Cons - risk of rectal damage, unlikely to resolve LUTS, risk of erectile dysfunction
Pros - no major surgery, low risk of urinary incontinence
What are the pros and cons of radical brachytherapy?
Cons - may worsen LUTS for 2-3m, radioactive seeds in prostate (protect contacts)
Pros - single treatment, less invasive, reduced risk of erectile dysfunction