28 - prostate ca Flashcards
prostate cancer risk if 1 first degree relative has it
2x
prostate cancer risk if >1 first degree relative has it
10x
% with true hereditary prostate ca
10%
3 criteria for hereditary pca
> /= 3 affected relatives, OR >/= 2 relatives with early onset < 55yo, OR in 3 successive generations
difference with hereditary cap
earlier onset only, same biologic activity
REDUCE trial - what was it
8000 men randomized to dutasteride vs placebo - 25% reduction in prostate cancer risk
PCPT trial - what is it
19K randomized to finasteride vs placebo. 25% risk reduction for prostate cancer on finasteride, but equal number of prostate ca deaths. Higher incidence of G7-10 due to overdetection bias (effect of volume reduction on tumor detection)
PCPT and “normal” PSA values - 2
11% cap in PSA <1, 30% cap in PSA 3.1-4
overall survival for all stages at 5 and 10 yrs
99% and 91%
PLCO - what did it show
80K men 10 yr f/u, no difference in disease specific mortality
problems with PLCO
high contamination in control arm, low biopsy compliance in screening arm
ERSPC - what is it
16K men. NNS 1400, NNT 50
where are most tumors located and %
75% peripheral zone> transition zone (20%)
periurethral duct prostate ca AKA
urothelial ca
% cap detected by DRE alone
20%
what kind of molecule is PSA
kallikrein-like serine protease
what molecule is PSA bound to when referring to free psa
a1-antichemotrypsin
where is free:total psa useful
risk stratifying those with PSA 4-10
is F:T PSA affected by finasteride
no
F:T PSA AKA
% free PSA
x% with pca with F:T <10%
55%
when is PSA doubling time useful
recurrent prostate ca
what kind of marker is PCA3
prostate specific mRNA marker for DD3 gene
PCA3 use
not as primary screening but to dictate need for repeat biopsy in men with persistently elevated PSA
PCA3 compared to PSA
higher sensitivity/specificity
PCA3 and prostatitis/BPH
independent of inflammation/prostate size
how to collect PCA3
agressive DRE - voided urine
AUA best practice policy for post biopsy abx - 1st line
FQ or 2nd/3rd gen cephalosporin
is low dose aspirin an absolute contraindication to biospy
no
is complication rate associated with # biopsy cores
no
3 indications for repeat biopsy
- rising/persistent psa, 2. suspicious DRE, 3. ASAP
detection rate for pca for TURP
8%
why not biopsy transition zone
low detection rate
ideal method of examining prostate apex path
“cone method”
strongest predictor of pca outcome
gleason score
significance of PNI in pca
unknown
prostate cancer distribution by north vs southern europe
more common in northern vs southern europe
PSA levels vary with which 3 things
age, race, prostate volume
urinary retention rate in saturation vs nl prostate biopsy
higher in saturation (swelling)
significance of baseline PSA
baseline >1.5 (@ 50 yo) is powerful predictor of subsequent cap (6-10x rr)
BMI and PSA
higher BMI= PSA hemodilution and lower [psa]. more likely to have agressive disease at presentation and suffer relapse
ACS PSA screening
no screening, discussion w patient regarding pros and cons
NCCN PSA scrreening
no screening, discussion w patient regarding pros and cons. start at 40 for high risk men, and 50 for avg risk
AUA PSA screening
baseline PSA at 40, if < 1 considered low risk and return at 45 yo
nccn very low risk cap criteria for AS
T1c, G6, PSA < 10, < 3 + cores w < 50% vol in each core, psa density < 0.15
AS and prostate ca specific mortality
5-10% esp if PSA doubling time < 3 yrs. nonprostate ca spcific mortality far outweighs prostte ca specific mortality
risk of progression requiring tx during AS
30%
treatment modalities and prostate cancer survival
prostatectomy is the only treatment modality to confur survival advantage over no tx (35% reductin in death/mets vs no tx up to 10 yrs)
recovery of erectile function post nerve sparing prostatectomy
50-90% recovery of some erection if potent beforehand, and upto 80% in pts < 60 yo
penile rehab?
it works
when is pelvic LN dissection considered not necessary
low risk cap
2 indications for early adjvant radiation
pT3, positive surgical margins
timing for giving early adjuvant radiation
once continence has returned
is early radiation better than salvage radiation (waiting for biochemical recurrence)
unclear, but salvage avoids treating everyone with T3
who benefits most from salvage radiation - 3
favorable biochemical recurrence characteristics (PSA <2, slow psa doubling time, long interval to failure after surgery)
what to do before salvage radiation - 2
restage with imaging (CT, bone scan) and DRE
PSA threshold post prostatectomy signifying recurrence
> 0.2 ng/dl
how exactly does EBRT work
photons damage cellular DNA
standard EBRT dose
70 gy over 7 weeks
how does androgen depravation therapy help in EBRT - 2
volume reduction of prostate (reduce number of cells, diminish collateral damage to bladder/rectum by shrinking prostate)
caveat to androgen ablation in EBRT
survival benefit wanes in > 65 yo with cardiac risk factors - consider cardiac eval
how far does dose go from brachy seed
2-3mm
radiation dose in brachytherapy - I-125 vs Pd-103
145 gy - I-125 vs 125 gy - Pd-103. same outcomes
limitations to brachy - 3
cant do in prostate > 60 cc, higher risk of retention with IPSS > 15, higher risk of incontinence if hx TURP
brachy + EBRT
done for intermediate - high risk disease
Post EBRT PSA doubling time and clinical relapse
PSAdt < 12 months = high risk early clinical relapse if untreated
significance of PSA rise post radiation
confirm with repeat psa to make sure rise is durable
factors predicting success of salvage surgery - 3
PSA< 10 preop, </= T3a, hx brachy or IMRT
radiation tx for locally advanced cap
ADT x 2-3 yrs + radiation = improved local and systemic control
micromets to nodes and tx
can complete surg and give ADT postop or radiation + ADT = survival benefit
risk factors for metastatic disease and survival in PSA recurrence - 3
time to psa recurrence (< / > 2 yrs), PSA doubling time < / > 9 mo, gleason score >/< PSA 8
main difference between GNRH agonist vs antagonist
no flare with antagonist, vs agonist
what class is degarelix
GNRH antagonist
nilutamide, biclautamide, flutamide class
NONsteroidal antiandrogen
nilutamide side effects - 2
interstitial lung disease, visual adaptation disturbances
risk of gynecomastia with antiandrogen and potential mgmt
50%, pretreatment with breast radiation
alternative to LHRH agonist - why better (2)/worse (1)
antiandrogen - fewer sexual side effects (loss of libido/ED), improved QOL with same survival but high risk of gynecomastia
why is DES not used for medical castration
high CV risk of mortality
only setting where adjuvant ADT assd w survival benefit
post prostatectomy LN positive disease
actual survival benefit of provenge
4.1 mo
exclusion criteria for provenge - 3
pain requiring narcotics, visceral mets, life expectancy < 6 mo
how to monitor response to provenge
no measurable way to detect response
party line on intermittent ADT
considerd safe with suggestion of improved QOL without negative effects on time to disease progression/survival
2 tx options for pts presenting with spinal cord compression
ketoconazole, degarelix
what does it mean when tumor is castrate resistant - 3
- tumor may produce its own androgen (autocrine), 2. amplify low levels of testerone ligand signaling through androgen receptor mutations or duplications, 3. or activation of AR through other ligands
2 caveats to labeling tumor as hormone refractory
- tumor may become hypersensitive to androgens –> dangerous to stop antiandrogen immediately, 2. may be sensitive to other hormonal manipulations
mgmt of RISING psa while recieving ANTIandrogen
1/3 patients will have PSA decline when antiandrogen is stopped.
docetaxel va mitoxantrone
3 month survival benefit with docetaxel
how is docetaxel administered
with prednisone
docetaxel side effects - 2 main
myelosupression and peripheral neuropathy
additional docetaxel side effects - 4
constipation, tearing due to deposition in tear ducts, onycholysis, fluid retention (peripheral/pulmonary edema)
significance of normalized psa while on docetaxel
33 mo survival vs 16 mo
best prognostic marker for survival while on docetaxel
> 30% reduction in PSA in first 3 months
circulating tumor cells and docetaxel
can be used to monitor treatment response and correlates with overall survival.
use of mitoxantrone + prednisone
palliation of pain + QOL once failed docetaxel, and carbazetaxel
main mitoxantrone toxicity
cumulative cardiotoxicity
type of bone remodeling seen with prostate cancer
osteoblastic - bone mets assd w increased bone formation aroud tumor deposits, however causes osteolysis
role of bisphosophonates in bone mets
stops osteolysis
what exactly does zolendronic acid do in prostate cancer - 3
delay in need for radiation, pathologic fx onset, bone pain
who gets zolendronic acid
castrate resistant (only). no role in hormone sensitive
2 side effects for zolendronic acid
renal failure, osteonecrosis of jaw
what is denosumab
inhibitor AB to block RANKL (mediates osteoclast-mediated bone resorbtion). prevents SRE
who gets denosumab
castrate resistant (only). no role in hormone sensitive
second line after failing docetaxel
carbazetaxel + prednisone
survival benefit of carbazitaxel
2 months
major side effect of carbazitaxel and mgmt
neutropenia (upto 8%) and prophylactically given GMCSF
indication for abiraterone
mcrpc who have recieved prior docetaxel
abiraterone MOA
blocks CYP450 c17 (lyase and hydroxylase) steps in testosterone synthesis in periphery and in tumor
electrolyte abnormalities while taking abiraterone - 2
hypokalemia and hypophosphatemia
infection/ stress while taking abiraterone or if steroid is stopped
get adrenal insufficiency
3 reasons for treatment discontinuation in abiraterone
AST/ALT elevation, urosepsis, cardiac failure
T1a,b,c
a/b - incidental histologic finding </> 5%, c - dx by needle biopsy due to elevated PSA
T2a,b,c
a - 1/2 one lobe but not both sides, c - both lobes
T3a/b
a - ECE, b - invades SV
T4
invades bladder, or adjacent structures
