Prostate and Bladder Cancer Flashcards
How much does the normal prostate weigh in a young adult?
20g
What are some parts of the prostate?
Apex = inferior portion, continuous with striated sphincter Base = superior portion, continuous with bladder neck
What cell type covers the prostatic urethra?
Transitional epithelium
Where is the verumontanum of the prostatic urethra located?
Just distal to the urethral angulation = ejaculatory ducts drain into either side
Where is the transition zone of the prostate located?
Surrounds prostatic urethra proximal to the verumontanum = only accounts for 10% of prostatic glandular tissue in young men
How common are cancers of the transition zone of the prostate?
Accounts for 20% of prostate cancers
Area gives rise to benign prostatic hyperplasia
Where is the central zone of the prostate located?
Cone shaped region that surrounds the ejaculatory ducts = 25% of glandular tissue in young men
How common are cancers of the central zone of the prostate?
Only accounts for 1-5% of prostate cancers
What are some features of the peripheral zone of the prostate?
Posteriolateral prostate = majority of prostatic glandular tissue, origin of up to 70% of prostate adenocarcinomas
What is the epidemiology of prostate cancer?
Most common malignancy in men in the UK
Second highest cancer mortality = 13% of all cancer related deaths in men in the UK
What is the course of prostate cancer?
Long natural history and indolent course = many patients die from other causes rather than causes directly attributable to the cancer
What is the aetiology of prostate cancer?
Precise cause unknown
Highest rate in Scandinavia and North America
Lowest rates in Asia
What age does prostate cancer tend to present at?
Peak age is 70-74
Rare < age 50
85% of cases are patients >65
What ethnicities are at higher risk of prostate cancer?
Black men at higher risk than Caucasians
Asians rarely develop it unless they move to the West
What are the genetic associations of prostate cancer?
Genetic abnormality on chromosome 1q, 8q, Xp and mutations in BRCA2
How does prostate cancer cluster in families?
Risk of CaP doubled with one first degree relative
Four fold increase with two first degree family members
How do most patients with prostate cancer present?
Most are asymptomatic and are picked up by PSA or abnormal DRE
What are some symptoms of prostate cancer?
Lower urinary symptoms, haematuria/haematospermia,
bone pain, anorexia, weight loss
Why are DREs important to do for patients with suspected prostate cancer?
75% of cancer are in the peripheral zone so can be palpated on rectal examination
What are some features of an abnormal prostate on DRE?
Asymmetry, nodule, fixed craggy mass
How good is DRE for identifying patients with prostate cancer?
50% of abnormal DREs are associated with CaP
30% with normal PSA and abnormal DRE will have CaP
What does an abnormal DRE mean for the stage of the prostate cancer?
Usually quite advanced = only 40% with abnormal DRE will have organ-confined disease
What is prostate specific antigen (PSA)?
Glycoprotein enzyme (kallikrein-like serine protease) = produced by the secretory epithelial cells of the prostate and involved in liquefaction of semen
What are PSA levels like normally?
In health semen levels of PSA are high and serum levels are low = prostate cancer increases serum levels
Is PSA a good prostate cancer tumour marker?
Not really = has 90% sensitivity but only 40% specificity
What are some other conditions that can cause PSA to rise?
Benign prostatic hyperplasia, prostatitis, UTI, retention, catheterisation, DRE
What must always be done before carrying out a PSA test on an asymptomatic individual?
PSA counselling
What areas should be included in PSA counselling?
Cancer identified in <5% of patients
TRUS biopsy = uncomfortable, 1% risk of significant sepsis and bleeding, may need repeat biopsy
Treatment may not be necessary or curative
What are the indications for a trans-rectal USS-guided biopsy (TRUS) to investigate prostate cancer?
Men with abnormal DRE/elevated PSA, previous biopsies showing PIN or ASAP, previous normal biopsies but rising PSA trend
How is a TRUS biopsy carried out?
USS probe passed through the rectum and prostate visualised in transverse and sagittal sections = 10 biopsies taken (5 from each lobe)
What are the complications of a TRUS biopsy?
0.5% risk of sepsis
0.5% risk of rectal bleeding
Vaso-vagal fainting
Haematuria/haematospermia for 2-3 weeks after
What are most prostate cancers?
> 95% are multifocal adenocarcinomas
What is the pattern of growth of prostate cancer?
Starts with local extension through prostatic capsule, to urethra, bladder base and seminal vesicles and with perineural invasion along autonomic nerves
Where are the most common sites for metastases from prostate cancer?
Pelvic lymph nodes and skeleton
What are the characteristic lesions of prostate cancer?
Sclerotic lesions
What is Gleason’s scoring for prostate cancer?
Gives score on the architectural appearance of the prostate glands rather than cytological features = good prognostic predictor
How is prostate cancer graded microscopically?
Grade 1-5 = initial feature of CaP is loss of basement membrane
What does the Gleason score increase with?
Microscopic loss of glandular structure and replacement by a disorganised malignant cell growth pattern
How is the Gleason grade written?
Two most abundant cell patterns are assessed and the added together to give a score between 2 and 10
What is T1-3 staging of prostate cancer?
T1 = clinically inapparent tumour not palpable/visible by imaging T2 = tumour confined within the prostate T3 = tumour extends through prostate capsule
What is stage T4 of prostate cancer?
Tumour fixed or invades adjacent structures other than seminal vesicles = bladder neck, external sphincter, rectum, levator muscles, pelvic wall
What is the N staging of prostate cancer?
N0 = no regional lymph node metastases N1 = regional lymph node metastases
What is the M staging of prostate cancer?
M0 = no distant metastases M1 = distant metastases
What imaging modalities can be used to stage prostate cancer?
Bone scan, MRI, CT scan
What are some broad classifications of prostate tumours?
Organ confined disease = T1-2, N0, M0
Locally advanced disease = T3-4, N0, M0
Metastatic disease = N1, M1
What are some factors that influence management of prostate cancer?
Category cancer belongs to, age, co-morbidities, life expectancy, patient preference, quality of life
How is organ confined prostate cancer managed?
Conservative management until further development
Active monitoring
Radical surgery or radiotherapy
What is done in active monitoring of prostate cancer?
Close surveillance of progression (short PSA doubling time and deteriorating histopathological factors)
What are some radical surgeries that can be done for prostate cancer?
Radical prostatectomy = complications of erectile dysfunction, incontinence and bladder neck stenosis
What are some radical radiotherapy options for prostate cancer?
EBRT or brachytherapy = complications are irritative LUTS, haematuria, GI symptoms, erectile dysfunction and incontinence
How is locally advanced prostate cancer treated?
Radiotherapy with neo-adjuvant hormonal therapy
Watchful waiting
Hormonal therapy
What prostate cancer patients are suitable to be managed with watchful waiting?
Asymptomatic patients with well and moderately differentiated tumours and <10 year life expectancy, patients who don’t accept treatment-related complications
What prostate cancer patients are suitable for hormonal therapy?
Symptomatic patients who need palliation of symptoms, unfit for curative treatment
How is metastatic prostate cancer treated?
Androgen dependent therapy
Diethylstilboestrol/steroids
Cytotoxic chemotherapy
What are some different forms of androgen dependent therapy?
Hormonal therapy = anti-androgens, LHRH analogues
Bilateral subcapsular orchidectomy
Maximal androgen blockade
What is the growth of prostate cancer cells under the influence of?
Testosterone and dihydrotestosterone
What are some features of testosterone?
Produced by testes (90%) and adrenals
Secretion regulated by HPG axis
Exerts negative feedback control of hypothalamic LH secretion
What happens to prostate cells if they are deprived of androgenic stimulation?
They undergo apoptosis
What does chronic exposure to LHRH agonists lead to?
Down-regulation of LHRH receptors = subsequent suppression of pituitary LH and FSH secretion and testosterone production
How do LHRH agonists cause a testosterone surge?
Initially stimulate pituitary LHRH receptors = induces a transient rise in LH and FSH release, and consequently elevates testosterone production
How do patients with a testosterone surge caused by LHRH agonists present?
20% of patients present with catastrophic spinal cord compression
How is a testosterone surge prevented when prescribing LHRH agonists?
Anti-androgen is given for cover 1 week before and 2 weeks after the first dose of LHRH injection
What are the side effects of LHRH agonists?
Loss of libido, erectile dysfunction, hot flushes and sweats, weight gain, gynaecomastia, anaemia, cognitive changes, osteoporosis
How do anti-androgens work?
Compete with testosterone and DHT for binding sites on their receptors in the prostate cell nucleus = promotes apoptosis and inhibits cancer growth
What is an example of a steroidal anti-androgen?
Cyproterone = side effects are loss of libido, erectile dysfunction, gynaecomastia (rare), cardiomegaly and hepatomegaly
What are the two types of anti-androgens?
Steroidal and non-steroidal
What are some examples of non-steroidal anti-androgens?
Nilutamide, flutamide and bicalutamide = sexual interest and libido are preserved, side effects of gynaecomastia, breast pain, hot flashes and hepatotoxicity
What does urinary bladder cancer require?
Lifelong routine monitoring and treatment = highest cost of any cancer from diagnosis to death
What is the most common urothelial cell tumour?
Transitional cell carcinoma = 90%
What are some rarer urothelial cell tumours?
Squamous cell carcinoma = 9%
Other (1%) = sarcoma, adenocarcinoma, undifferentiated, benign mesodermal
What are the types of transitional cell carcinomas?
Papillary type (80%) = 50% are infiltrative malignancies Non-papillary type (20%) = all malignant
What can the classification of transitional cell carcinomas range from?
Well differentiated papilloma (grade 1) to malignancy (low grade and superficial to high grade and invasive)
How are transitional cell carcinomas imaged?
Excretory urogram, sonography, retrograde pyelogram, computed tomography, angiography
What are the usual features of transitional cell carcinomas?
Tend to be multicentric and bilateral = bilateral in up to 10% (synchronous or metachronous)
How common is bladder carcinoma in patients with ureteric or pelvic cancer?
Occurs in up to 50%
What are some features of urinary bladder carcinomas?
Four times more common in men, patients usually age >50, investigated using cystoscopy or excretory urography (insensitive for diagnosis)
What is a radiological sign of urinary bladder cancer?
Halo sign
What uroepithelial tumours undergo calcification?
Transitional cell, squamous cell and urachal carcinomas
