prostate cancer Flashcards
describe the anatomy of the prostate gland
The gland is divided into 4 zones: peripheral zone (largest), central zone, fibromuscular zone and transitional zone.
the urethra goes through the prostate.
peripheral zone can be felt on DRE.
in older men the transitional zone grows and dominates by compressing other zones.
comprised of secretory luminal cells - well differentiated epithelial cells that secrete PSA and have androgen receptors
explain 3 precancerous conditions in the prostate
prostatic intraepithelial neoplasia (PIN): cytologically atypical epithelial cells can be divided into low and high grade.
atypical small acinar proliferation - biopsy shows small atypical acini but not diagnostic of adenocarcinoma. can be a predictor of later prostate cancer
proliferative inflammatory atrophy - epithelial cells appear to be growing rapidly - may lead to adenocarcinoma
where do majority of prostate cancers arise from and what is characteristic about them?
majority occur in peripheral zone and arise from acini or proximal ductal epithelium - adenocarcinoma develops.
generally multifocal with tumour present throughout the gland
often heterogenous - complicates treatment and prognosis
but majority are slow growing
where do prostate cancers metastasise to?
locally - rectum, bladder neck and seminal vesicle
via lymphatics - hypogastric, external iliac and presacral nodes
haematogenously - mainly to the BONE also liver and lung.
what are the risk factors of prostate cancer?
age - rarely occurs before 60 and incidence rapidly rises after
ethnicity - black>white>Asian
family history - only significant if a first degree relative with prostate cancer before age 60
diet and lifestyle
genetics - BRCA1/2 or HPC1 and 3 = hereditary prostate cancer
PSA - increased PSA testing results in more PSA driven biopsies and thus increased incidence of cancer because asymptomatic low risk cancers are being detected.
list the clinical features of prostate cancer.
can be assymptomatic
direct symptoms:
- urinary symptoms - frequency, nocuturia, haematuria, poor flow, hesitancy , incomplete emptying
lymphadenopathy - inguinal, paraaortic, supraclavicular, axillary.
metastasis:
- bone pain, fractures
- signs of spinal cord compression
- lung metastasis - pleural effusion, consolidation, etc
- liver metastasis - hepatomegaly, jaundice and ascites
paraneoplastic: anaemia, cachexia (rarely get weight loss), dehydration, fatigue, DIC
other - haematospermia, AKI from obstruction, confusion
what do you expect to find on DRE in someone with prostate cancer?
hard, irregular, nodule felt
asymmetrical
lack of mobility
what is the IPSS
international prostate symptom score - a scoring tool to assess severity of urinary symptoms.
many conditions other than prostate cancer can give similar urinary symptoms
what investigations are required to aid diagnosis and staging of prostate cancer?
full history and examination including DRE
routine bloods - PSA, FBC, U+Es, acid phosphatase and ALP
if DRE and PSA are abnormal = TRUS guided biopsy
(TRUS = Transrectal ultrasound)
urinalysis - rule out UTI
staging
- CT/ MRI - invasion, nodes and other metastasis
- CXR/ Xray bones - if indicated
- isotope bone scan if PSA is very high
what can PSA levels tell us about likelihood of prostate cancer?
PSA can be low and still have prostate cancer
there are other causes of raised PSA
therefore not 100% perfect marker
however if very high (1000s) quite likely to be cancer
also can help to monitor treatment and progression of cancer.
what is an alternative method of biopsy other than TRUS guided?
Transperineal template biopsy
- more accurate and no sepsis risk
- but need general anaesthetic
what 3 things are needed to definitely diagnose prostate cancer?
PSA
DRE
TRUS guided biopsy
sometimes patients don’t present with urinary symptoms and present with metastatic disease. which type of bone cancer is prostate cancer until proven otherwise?
sclerotic bone lesions in older men are prostate cancer until proven otherwise.
what is the gleason score?
Gleason score is a score given to biopsy microscopy slide depending on its level of differentiation. ranges from 1 to 5 (1 being well differentiated with discrete glandular formation and 5 being poorly differentiated with loss of glandular architecture)
the final gleason score takes the score of the most common score and the second most common score from a biopsy and adds it. e.g. score 7 (4+3) = the most common score found within the biopsy was score of 4 and the second most was score of 3.
therefore final gleason score can range from 2 to 10
how can we divide the Gleason score into 3 categories?
final gleason score:
- <4 = well differentiated, low risk
- 5-7 = moderate differentiation
- > 7 = poorly differentiated, high risk of progression.
what is the best predictor of prognosis of prostate cancer?
Gleason score
what is the gleason grade?
the gleason scores can be converted into grades:
grade 1 = gleason score 2-6 = low grade
grade 2 = gleason score 7 (3+4) = intermediate grade
grade 3 = gleason score 7 (4+3) = high grade
grade 4 = score 8 = high grade
grade 5 = score 9-10 = high gradek
how is prostate cancer staged?
TNM
T0 = no palpable tumour
T1 = tumour in one lobe
T2 = involves both prostate lobes
T3 = infiltrates out of prostate and involves seminal vesicles
T4 = extensive tumour, fixed and infiltrating local structures.
N0 = no nodes N1 = ipsilateral nodes N2 = bilateral nodes N3 = fixed regional nodes N4 = Juxtaregional nodes
M1 = metastasis
the overall risk of localised prostate cancer metastasing is divided into low, intermediate and high. describe each risk level.
low risk: PSA <10ng/ml, gleason 6 or less, stage T1 -T2a
intermediate: PSA 10-20, gleason 7, T2b
high : PSA >20, gleason 8-10, T2c or above
what are the clinical prognostic factors for prostate cancer?
clinical tumour stage,
gleason biopsy grade
PSA
what is the prognosis for metastatic prostate cancer?
2-4 yrs
what factors influence the treatment of prostate cancer?
age PSA DRE biopsy and gleason grade MRI and bone scan
how can you estimate the T stage from DRE?
- T1/2 = localised
- T3 = lots of irregularity
- T4 = rock hard
what do you assess on biopsy in prostate cancer?
pleomorphism Nuclear to cytoplasmic ratio hyperchromatism mitotic bodies irregularity extent - how many samples have cancer, how many nodes have cancer.
what is the indication for referral of suspected prostate cancer?
2ww referral if:
- PSA above specific age range OR
- DRE prostate feels malignant
consider doing a DRE and PSA in the first place if there are urinary symptoms, visible haematuria or erectile dysfunction
should all prostate cancers be treated?
no depends on the risk
e.g, often low risk ones can persist for many years and patient will die of something else, in which case the side effects of treatment are more damaging than the cancer itself
therefore also depends on age, comorbidities and performance status
what are the treatment options for clinically localised prostate cancer?
watchful waiting
active surveillance
radical prostatectomy
external beam radiotherapy/ brachytherapy
high intensity focused ultrasound - only offered privately
what is the cut off gleason grade where a prostate cancer is considered low risk and surviellence/ watchful waiting is offered rather than active treatment?
grade 6 = low risk of metastasising therefore just monitor
grade 7 = high risk so worth treating.
what is watchful waiting?
no active treatment is given until symptomatic or PSA rises i.e. tumour progresses.
When tumour progresses can give androgen deprivation therapy - this is not curative but reduces harm made by tumour to achieve the best balance between tumour effects and treatment side effects.
this is good for those with a life expectancy <10 yrs
what is active surveillance?
for low risk disease
PSA and DRE 6 monthly
when disease progresses (PSA rises, DRE suggestive of progression) then curative treatment is initiated
this assumes that there is no difference in prognosis in delaying and immediate treatment.
avoids over treating those who have cancers that will never progress
when is radical prostatectomy indicated?
only for those with clinically localised disease and little/ no systemic comorbidities due to risk of major surgery.
good for those with a life expectancy >10yrs
what are the complications of radical prostatectomy?
anaesthetic risk
incontinence
impotence
what does radical prostatectomy include?
complete removal of prostate and blood supply.
+ pelvic node dissection in those with slightly higher risk
when is external beam radical radiotherapy/ brachytherapy indicated
clinically localised prostate cancer
however for those who are no fit enough for surgery (prostatectomy)
also for locally advanced disease
what are the complications of radiotherapy of prostate?
damage to adjacent organs - diarrhoea, chronic proctitis, impotence
incontinence (risk is less than for prostatectomy)
how is locally advanced disease (T3/4 ) treated?
adjuvant hormones and external beam radical radiotherapy (if brachytherapy then the dose is strong enough not to need hormones alongside)
can consider orichidectomy - reduced stimulation for tumour growth. however associated with psychological problems, hot flushes and impotence
how is metastatic prostate cancer treated?
it is incurable but treatment options include:
- Orchidectomy = surgical castration - reduce testosterone to inhibit tumour growth
- medical castration = LHRH agonists + anti androgens
palliative care:
- single dose radiotherapy
- bisphosphonates for bone mets
- analgesia
explain the theory behind LHRH agonists for the treatment of prostate cancer. Why are antiandrogens also needed?
LHRH agonists bind LH receptors and initially increase testosterone production and thus the cancer will flare for the first 2 weeks. Eventually the system will become exhausted and androgen secretion will cease and tumour growth will be reduced.
however in these first two weeks, the progression of cancer is dangerous and can lead to spinal cord compression and thus antiandrogens are given 3-7 days prior to treatment and stopped 3 weeks after LHRH agonists have been started.
what drug can be added to those people with metastatic prostate cancer but performance status 0-2
docetaxel = chemotherapy
what treatment is available to castrate resistant prostate cancer?
NICE says
- add anti androgen (Bicalutamide)
- consider prednisolone + docetaxel if performance status is 0-2
what can be done for those individuals with performance status 0-2 but resistant to docetaxel (with metastatic disease and castrate resistance)?
2 options:
- Enzalutamide - 5x stronger antiandrogen than bicalutamide
- Prednisolone + Abiraterone
what is abiraterone?
drug that inhibits cytochrome P17 - which is normally involved in testosterone production
what are the complications from the treatment of prostate cancer?
flare - bone pain, obstructive AKI, spinal cord compression
hot flushes = can give medroxyprogesterone for 10 weeks
sexual dysfunction
osteoporosis - can give bisphosphonates
gynaecomastia (due to antiandrogens) - prophylactic radiotherapy of breast buds can help
fatigue
how can we prevent prostate cancer?
hormone manipulation:
- some people have a reduced level of 5a reductase (enzyme converting testosterone to a more potent form) and these people are at reduced risk of developing prostate cancer. Finasteride is a competitive inhibitor of 5a reductase and can be given to those at high risk of prostate cancer to help reduce their risk
antioxidant - green tea, exercise, healthy diet
early detection and screening - screening for raised PSA is not recommended but opportunistic screening is offered.
what are the causes of raised PSA?
prostate cancer BPH urinary infection acute urinary retention prostatic inflammation
should we screen for prostate cancer?
raised PSA is non specific for prostate cancer.
10% of men aged 50-70 have raised PSA and only 25% of these have prostate cancer and thus screening would result in many false positives creating anxiety for no reason.
therefore the issues are:
- overdiagnosis
- over treatment - side effects - without screening the low risk asymptomatic ones will not be treated and thus wont suffer from side effects of treatment.
- diagnosis and treatment reduce quality of life. - no cost effective to diagnose and treat everyone with low risk disease
what is the function of PSA?
serine protease
anticoagulation of semen
