Prostate Flashcards
survey or rad prostatectomy?
PIVOT trial: NEJM 2012 Wilt: 14% of target enrolled; no difference in disease-specific mortality; if: higher PSA, higher baseline risk, higher gleason–> trend of benefit for surgery
active surveillance regimen for diagnosed cancer
repeat biopsy at baseline, then upon progression of PSA, if no progression every 3 years; q6mo PSA and DSE
PSA rise–> when to think local
if extra capsular extension and late rise–>likely local;
PSA doubling time (PSADT) cutoff for risk estimation
if <3mo after surgery/radiation (1/5 of population), likely to develop mets and die of cancer
castration resistant
tumors not hormone-refractory, they just grow with lower levels
intermittent androgen deprivation
reduced toxicity, does not delay castrate-resistance, improved quality of life: NEJM Hussain (if low PSA at 6 months, do intermittent: unable to conclude non-inferiority); other trials show equivalence–> NOW STANDARD to treat 6 months then d/c if PSA drops to <4
if PSA goes down and bone scan worse
flare phenomenon–> repeat second scan, look for NEW lesions
TROPIC trial
cabazitaxel in docetaxel-refractory–> OS benefit
enzalutamide/xtandi
binds and inhibits AR, also inhibits transport to nucleus and binding to DNA (also taxanes inhibit transport to nucleus)
prostate ca epi
1st in men 220k, 2nd most cause of death
rising PSA with no mets
60,000 of patients, proportion develop clinical mets
castrate resistant
means that castrate levels of testosterone but still progression
paradigm for prostate ca treatment
intervene if Sx, or if risk of significant event might occur is high
prostate cancer biospy
12-14 cores
prostate cancer screening
T3a- extracapsular, T3b- seminal vescles
nodal disease in prostate ca
pelvic nodes good prognosis, outside pelvis bad
calculating risk of early stage prostate
need nomogram, which is still work in progress. T-stage alone insufficient
localized prostate cancer risk assessment
if low risk, recommend 2nd biopsy. repeat biopsy with 24-30 cores to ensure sampling. alternative is MRI prostate to look for dominant lesion. low risk if no lesion. biopsies being guided using fused MRI/US imaging for adequate sampling
active surveillance scheduling
every 6 months
biochemical recurrence mgmt
use nomogram to predict liklihood of localized recurrence and benefit from RT
first line therapy with PFS rise
use nomogram. if <3month PSA doubling, more likely to have mortality. treat with antigen depletion (castration)
androgen depletion–> intermittent or continuous?
GnRH agonist + AR antagonist for 7 months for 7 months, . reduced toxicity and improved quality of life. does not delay development of resistance. non-inferiority. 13 trials–> no difference.
bisphos or denosumab in prostate
shown to delay SRE
causes of castrate resistance
up regulation of androgen receptor, or up regulation of androgen synthesis
slow drift up of PSA with enzalutamide
do not stop…still effective. symptom-based may be way to go
abiaraterone versus enzalutamide
prior response doesn’t predict response, but responses are lower in patients who don’t respond to one
high volume (4+ bone lesions) newly diagnosed metastatic prostate cancer
unsure of addition of docetaxel at front-line, one trial showed survival benefit, another showed no difference
DRE palpation
only peripheral zone, 70% of cancers. transition zone not evaluable
familial prostate
10%; highest risk SNP is in HOXB13 TF
adeno confirmation v. benign
expresion of alpha-methylacyl-coenzyme A racemase
translocations in pr ca
TMPRSS2-ERG fusion.
chemoprevention
analysis shows that you can avoid 4 low-grade tumors for 1 high grade- not recommended for healthy men. No OS benefit
AUA PSA recommendations
shared decision for age 55-69; otherwise no
PSA predictors
PSA 4: 23% PPV; PSA velocity >0.75/yr and PSA 4-10–> suspicious
number cores needed for TRUS Bx
12
free psa
% less than 25% is associated with +cancer. not recommended clinically to make decision
pelvic MRI recommendation
if T3/T4 (thru capsule or fixed/invasion) or nomogram LN risk >20%.
bone mets prostate
more often blastic.
bone scan recommended if
PSA >20, gleason 8, T3/T4 (capsule invasion), or Sx
PSA elevation after prostatectomy
median 8 years to Sx; higher risk - time to progression short, high glassine, high doubling time
Tx of PSA elevation after prostatectomy
no gold standard of whether to start ADT. can do intermittent with similar disease-specific survival
RT v. prostatectomy v. observe
can use nomograms.
biochem relapse after RT
nadir + 2.0 points
RT dose for prostate
78-79Gy.
ADT after prostate RT
needed for intermediate disease (6 months, if PSA velocity >2.0/yr). if node-posalsitive, need 2 years adjuvant ADT.
RT following prostatectomy
pT3 (capsule penetration), positive margins, detectable PSA after surgery.
salvage RT following prostatectomy
consider if PSA relapse and low risk features (i.e. >1 yr from surgery, glee 7, no LN or seminal vesicle invasion at surgery)
denosumab to prevent fracture on ADT
need 60mg SQ every 6 months. effective
bone flare on ADT
3-6 months after initiation of therapy
PSA to assess initial ADT response
7 month PSA: 4 high risk
ADT combined blockade versus just GnRH
modest improvement in survival. anti-androgen alone is inferior.
anti-androgens
flutamide, bicalutamide, nilutamide.
ADT after prostectomy
no
intermittent v continuous ADT for metastastic
data not conclusive. intermittent not non-inferior. however meta-analysis shows same OS and improved QOL
docetaxel + ADT for newly metastatic
survival benefit for visceral disease, or 4+ boney sites. only 1 study
medical castration
defined as testosterone
newly castrate resistant disease
trial of anti-androgen withdrawl, and consider second ant9-androgen or ketoconazole or hydrocortisone (non-cross-resistant sometimes)
abiatarone
oral CYP17 inhibitor + prednisone, blocks androgen synth. 1g daily plus prednisone 5mg BID
enzalutamide
another potent anti-androgen,
sipuleucel-T
autologous vaccine of prostatic acid phosphatase and G-CSF, q2wks x 3
docetaxel for prostate
75mg/m2 q3wk + prednisone
cabazitaxel for prostate
25mg/m2 + 10mg day predinsone. improved survival. consider G-CSF given high rates of neutropenia
alpharadin
approved for symptomatic bone mets (cannot have visceral disease), improved survival.
regimens for adrenocortical caricinoma
surgery. poor prognosis if >5cm. mitotane. adding EDT (etoposide, doxorubicin, cisplatin) improves PFS but not OS.
