Flashcards in 5/2 Prostate Cancer Deck (58):
sx of prostatitis?
dysuria, frequency, urgency, low back pain
causes of prostatitis?
chronic: bacterial or abacterial (most common)
what is PSA?
serine protease that is responsible for semen liquefaction
why does PSA increase?
- prostate size
- disruption of cellular architecture (prostate cancer, prostatitis, BPH, prostate massage, prostate bx)
it is organ-specific but NOT cancer specific
3 different ways that PSA can be measured?
kinetics: ∆ over time
density = ratio of PSA to size of prostate
% free = lower % free correlates with higher risk of prostate cancer
benign prostatic hyperplasia (BPH) - common in what age group
BPH - what is it? where does it often occur?
Hyperplasia of the prostate resulting in a smooth, elastic, firm nodular enlargement
usually of LATERAL + MIDDLE lobes (aka TRANSITION ZONE)
compresses the urethra into a vertical slit
∆ btwn microscopic BPH and macroscopic BPH?
Microscopic BPH - histologic evidence of cellular proliferation
Macroscopic BPH - enlargement of the prostate due to microscopic BPH
Symptoms of BPH?
What happens if it's not treated?
- difficulty with starting or stopping the stream of urine
- distension and hypertrophy of the bladder, hydronephrosis, UTI
- chronic obstruction -> bladder dysfunction or spasticity, resulting in poor bladder emptying, urgency, frequency
how does BPH result in hematuria?
prostate has a lot of veins on its surface; as it grow, the veins are prone to rupture, resulting in blood in the urine
What the heck is LUTS?
*LUTS (Lower urinary tract symptoms) complex of voiding symptoms (straining, hesitancy, urgency, frequency) that may or may not be caused by macroscopic BPH
term used when the precise cause of urinary dysfunction is unknown
What PE would you do on a patient with BPH?
DRE - est. prostate volume (size ≠ symptom severity)
Focused neurological exam - anal reflex, perianal sensation, gross motor exam neurological dysfunction.
He didn't say, but if this was actually prostate cancer, it can metz to the spinal column and cause neurological compromise (cord compression can cause bladder/bowel incontinence and decr lower extremity sensations/reflexes)
What are some tests that you can run on a patient with BPH?
Purpose of TRUS in BPH?
measure prostate volume
Purpose of Urinalysis in BPH?
r/o UTI, detect hematuria
Purpose of Needle Bx in BPH?
Purpose of Uroflow in BPH?
determine presence of obstruction (= low flow)
Purpose of urodynamics in BPH?
determine presence of obstruction vs contractility
obstruction = bladder generates high pressure + low flow
impaired contractility = low bladder pressure + low flow
in what cases would you recommend watchful waiting for patients with BPH?
What would you recommend patients to do during this period?
when symptoms are not bothersome since risk >> benefits and cost of treatment
recommendations: decr. fluid intake, esp if they have urgency/frequency, avoid diuretics, caffeine, EtOH, timed voiding
terazosin MoA? indications?
α1 antagnoist -> smooth muscle relaxation to decrease bladder outlet obstruction and improve emptying, flow rate, and symptoms
Used for BPH
tamulosin “Flomax” MoA? indications?
selective α1 antagnoist -> smooth muscle relaxation to decrease bladder outlet obstruction and improve emptying, flow rate, and symptoms
same as terazosin, but with fewer ADRs
Used for BPH
(5α-reductase inhibitor, 5ARI) = blocks T -> DHT conversion, resulting in decreased prostate size
Used for BPH (also male-pattern baldness..oddly)
- decr. libido, ejaculatory disorder, impotence
- breast enlargement (incr T available for conversion to E)
potential risk for high-risk prostate cancer
MoA of Anticholinergic Rx in BPH? What must you monitor if you give this to a patient?
block cholinergic receptors in the bladder that enable contractility (good for men with overactive bladder sx caused by chronic obstruction)
need to monitor PVR (post-void residual) to ensure that these patients don’t develop urinary retention
When is surgery indicated for BPH?
What are some of the procedures that you can do?
when BPH is refractory to behavioral + pharmacological Rx
- TURP – scrape out the extra prostate tissue from periurethral regions
- Laser prostatectomy – ablate or vaporize the prostate
- Prostatectomy – usually done for very large prostates
Histologically, what should you see in BPH?
presence of BOTH stromal (basal) + epithelial elements
prostate cancer - common age of occurrence?
where does CaP usually occur? What type is most common?
posterior lobe (peripheral zone)
causes of CaP?
multifactorial - androgens, inflammation, age, race, family Hx
tumor markers of CaP?
PAP (prostatic acid phosphatase)
PSA (usually incr. total with decr. free fraction)
How does CaP progress if it is not treated?
metastasis - OsteoBLASTIC metz to bone may develop in late stages, as indicated by lower back pain and incr. in serum ALP and PSA
if CaP locally invades, what structures does it affect? classic symptoms?
extraprostatic extension or seminal vesicles; rarely rectum
- bladder outlet obstruction that is unresponsive to Flomax
- hematuria (due to incr vascularity)
- ureteral obstruction due to invasion into the bladder, resulting in Hydronephrosis and renal failure
if CaP metz, where does it usually go? what are the classic symptoms and labs?
OsteoBLASTIC metz to bone may develop in late stages
- bone/back pain (vertebral involvement can result in nerve compression)
- pathological fractures
- neurological compromise (cord compression can cause bladder/bowel incontinence and decr lower extremity strength or sensation)
- weight loss
incr. in serum ALP and PSA
What tests would you order to dx CaP?
DRE – assess prostate size, nodules (impt for clinical staging, extent of nodularity)
Needle Bx – TRUS guided – 12 cores (sextant biopsy) of the peripheral zones (sometimes transitional)
Bone scan – for metastatic diseases
Cap Treatment? (general)
Hormone Tx (1st line)
Chemotherapy (2nd line)
What is the purpose of hormone Tx in CaP?
Androgen Deprivation Tx (ADT)
surgical castration (ouch....)
medical castration using
- leuprolide (Lupron) - LHRH agonist)
- Androgen Receptor blockers
MoA of leuprolide?
Impt consideration when giving this drug?
LHRH agonist – causes an initial LH surge (and T production), but eventually results in a loss of phasic stimulation -> decr. LH -> decr. T production by Leydig cells to the level of an orchiectomy (shuts down hormone axis).
MUST start an androgen receptor blocker 2 wks prior to starting due to initial LH surge/ T production
ADR of leuprolide?
fatigue, hot flashes, mood changes, libido, erectile dysfunction, bone density, CVD
MoA of Androgen Receptor blockers ?
competitively binds androgen receptor;
steroidal (cyproterone acetate)
nonsteroidal (flutamide, bicalutamide)
MoA of Ketoconazole?
interferes with CYP450 pathways (blocks production of steroids); RAPID effect (testosterone to castrate levels in 4 hrs)
MoA of o Abiraterone?
selective and irreversible inhibitor of CYP17A, results in an extreme lowering of testosterone (<1ng/mL)
Why is chemoRx a second line therapy for CaP?
Which one is commonly used?
all patients eventually develop hormone-refractory cancers due to somatic alterations of the androgen receptor that can be activated by E, progestin, etc
Docetaxel = 1st line chemoRx
MoA of Docetaxel?
induces apoptosis by inhibiting microtubule depolymerization and blocks anti-apoptotic signaling
prolongs progression and overall survival, decr. pain, and improves QOL.
ADR of Docetaxel?
**myelosuppression, fatigue, edema, neurotoxicity, changes in liver function
What would you use to treat CaP bone metz?
MoA of bisphosphonates? ADR?
decr. bone resorption by inhibiting osteoclasts
decr. incidence of skeletal events caused by the prostate cancer
ADR: jaw osteonecrosis
What is D'Amico?
risk categories for prostate cancer
- low risk: PSA < 10, Gleason 6
- intermediate risk: PSA 10-20, Gleason 7
- high risk: PSA ≥20, Gleason 8-10
prognosis of LOW grade PIN in CaP?
usually an indolent course with a high cure rate
require active surveillance since local progression and metz may develop long-term (>15yrs)
prognosis of HIGH grade PIN?
Architecturally benign prostatic ducts lined by cytologically atypical cells; considered a precursor to cancer
repeat biopsy in 2-3 years
prognosis of ASAP?
"Atypical small acinar proliferation”
suggestive, but NOT diagnostic of cancer, though the likelihood of cancer increased 40-50%
repeat biopsy in 3 months
evidence of HIGH grade CaP?
- Perineural Invasion – usually path of least resistance for the cancer to spread (rather than invading through the thick stroma)
- fused glands
- single sheet of cells
hormonal Rx then chemoRx
Hx for CaP Adenocarcinoma?
multiple glands that are lined by crowded epithelial cells w/ prominent nucleoli
loss of basal cell layer = malignant
Hx for High grade PIN?
- crowded epithelium with lots of nuclei
- basal layer is still preserved (ø breaking through the BM)
What is the gleason score based on?
architectural features (glandular profiles and the degree of stromal infiltration)
NOT cytologic features
why are there 2 numbers in the gleason score?
many prostate cancers do not have a uniform appearance (>1 gleason pattern), it is usually given 2 grades
primary grade = predominant pattern
secondary grade = subordinate pattern
gleason score = primary grade + secondary grade
General schema of the gleason grading?
Grade 1/2 = well defined; not usually scored!
Grade 3 = crowded glands infiltrating btwn benign glands
Grade 4 = glands coalescing to form cyst-like structures
Grade 5 = glands fuse to become single cells
What is Staging based on? What are the 3 categories?
defined by location of tumor
T1 - clinically inapparent tumor neither palpable nor visible by imaging
T2 - Tumor confined within prostate
T3 - Tumor extends through the prostate capsule
T4 - Tumor is fixed or invades adjacent structures other than seminal vesicles (external sphincter, rectum, bladder, levator muscles, and/or pelvic wall)
M0 No distant metastasis
M1 Distant metastasis
- M1a: Non-regional lymph node(s)
- M1b: Bone(s)
- M1c: Other site(s) with or without bone disease