B8.048 Prework 2: Evaluation and Treatment of Prostate Cancer Flashcards
incidence of prostate cancer
1 in 9 men will be diagnosed
prostate cancer mortality
1 in 41 men will die of prostate cancer
risk factors for prostate cancer
age
race
family history
familial cancer syndromes
impact of race on prostate cancer risk
AA men
- 1.6x incidence
- 2.4x mortality
impact of family history on prostate cancer risk
father or brother: 2-3x incidence
2 first degree males: 5x increased incidence
impact of familial cancer syndrome on prostate cancer risk
BRCA 1/2: 4.5-8.6x incidence
Lynch: 10x incidence
signs of prostate cancer
most often: NONE
sometimes:
- prostate nodule
symptoms of prostate cancer
most often: NONE sometimes: -obstructive urinary symptoms -hematuria -pain -weight loss -fatigue
biology of prostate cancer
hormonal cancer
LHRH from hypothalamus > LH from pituitary > T from Leydig cells + T from adrenal gland
impact of T on prostate cells
converted to DHT
DHT binds to androgen receptor (AR) > AR dimerizes and translocates into nucleus> AR binds to DNA > increased PSA, increased growth, increased survival of the cell
grade groups of prostate cancer
1: gleason 3+3
2: gleason 3+4
3: gleason 4+3
4: gleason 8
5: gleason 9-10
* *correlates to risk of recurrence after treatment
clinical staging of prostate cancer
all based on DRE
if you can feel it: it is a higher stage (T2-T4)
T1 = not palpable
T2 = palpable within prostate
T3 = extraprostatic tmor that is not fixed or does not invase adjacent structures
T4= tumor is fixed or invades adjacent structures other than the seminal vesicles (external sphincter, rectum, bladder, levator, pelvic wall)
what is risk stratification based on
clinical stage
PSA
grade group
clinically insignificant prostate cancer
very low and some low risk -grade group 1 AND -PSA < 10 AND -non palpable disease
clinically significant prostate cancer
grade group 2-5
OR
PSA > 10
OR palpable
3 ways of spreading of prostate cancer
- locally
- lymph
- hematogenous
staging studies for prostate cancer
- CT/MRI: used in intermediate risk prostate cancer and above to look for nodal involvement
- bone scan
when is a bone scan indicated
PSA > 20 grade 4-5 cT3b N1 on scans symptoms (bone pain, obstruction)
treatment options for prostate cancer based on staging and risk groups
active surveillance
radical prostatectomy
radiation therapy
systemic therapy
what is active surveillance
monitoring of low/very low risk prostate cancer (clinically insignificant) with deferred intervention on identification of progression
rationale for active surveillance
grade group 1 prostate cancer is unlikely to metastasize or cause harm
avoid treatment harm
active monitoring reduces risk of mis classified higher grade disease
what % of patients will undergo treatment within 5-10 years of starting active surveillance
25-50%
what are curative intent options
radiation and surgery
when is curative intent indicated
localized: cT1-2N0M0
locally advanced: cT3N0-1M0
what is a radical prostatectomy
removal of prostate and seminal vesicles
- can be open or robotic (95%)
- +/- removal of the pelvic lymph nodes, indicated if predicted risk of nodal disease is >2%
pros of prostatectomy
ultimate biopsy
-40% of the time a biopsy is inconsistent with the final pathology
can improve urinary symptoms if present
ability to give radiation as an adjuvant treatment in the setting of aggressive disease or recurrence
cons of prostatectomy
incontinence: 2-5% at 1 year post op
-management: pelvic floor physical therapy
erectile dysfunction: 20-25% at 1 year post op
-related to impact of surgery on parasympathetic nerves adjacent to the prostate
-management: PDE5 therapy, penile injection therapy, vacuum erection devices
what is radiation
delivery of energy to tissue to exact DNA strand breaks for cellular death
types of radiation
external beam radiotherapy
stereotactic body radiotherapy
brachytherapy
pros of radiation
non-invasive no recovery time negligible risk of urinary incontinence no immediate impact on erectile function -expedites normal age related decline in erectile health tho (eventually evens out w surgery)
cons of radiation
paired with androgen deprivation therapy if intermediate or high risk
irritative urinary/bowel side effects
-can make existing symptoms worse
hard to salvage with additional local therapy in the setting of failure
ADT courses with radiation
grade group 3: 6 months of ADT
grade group 4/5: 3 years of ADT
follow up after curative intent treatment
PSA checks at a decreasing frequency over 5-10 years
-q3mo for 1 year, q6mo for 1 year, then yearly
management of treatment related side effects
definition of biochemical recurrence
post surgery: PSA > 0.2
post-radiation: PSA > 2.0 + nadir
treatment of biochemical recurrence
radiation if prior surgery
otherwise: simple ADT if after radiation
mechanism of ADT
impairment of the testosterone-androgen receptor interaction
-results in arrest of cell growth
side effects of ADT
hot flashes fatigue decreased bone mineralization decreased muscle mass impotence/decreased libido weight gain/metabolic syndrome CVD risk
different ADT options
all work on H-P-T/A axis hypothalamus -LHRH antagonist -LHRH agonist -estrogen testis -orchiectomy adrenal -CYP 17:20 lyase inhibitors target tissue -anti-androgens (block binding to receptor)
LHRH antagonist
degarelix
degarelix mechanism
prevents activation of gonadotropin releasing hormone receptors > no LH > no T
leuprolide mechanism
binds to and over stimulated the gonadotorpin releasing hormone receptor
- results in and initial stimulation of the receptor > T surge
- within 2 weeks, receptor down-regulates > no more LH > no T
LHRH agonist
leuprolide
antiandrogens
ketoconazole
5a reductase inhibitors
bicalutamide
enzalutamide
bicalutamide mechanism
competitive inhibitor of the androgen receptor
-can be used at the initiation of LHRH agonist therapy to block the effects of the T surge
interesting side effect w biclutamide
breast pain/tenderness
does not reduce T levels > increased peripheral conversion to E
more bioavailable T bc less is working in tissues
how long does first line hormonal therapy typically work after failed local therapy
8-10 years
what is the pathophysiology of castration resistant prostate cancer
prostate cancer is hormonally driven
with prolonged hormonal suppression, the prostate cancer cells will develop the ability to grow despite castrate levels of T
treatment for CRPC
advanced ADT (abiraterone, enzalutamide) chemotherapy (docetaxel)
enzalutamide mechanism
- prevents T binding to AR
- prevents translocation of the AR to the nucleus
- prevents binding of the AR to the DNA
* *give in conjunction with typical ADT
mechanism of abiraterone acetate
inhibition of CYP17:20 lyase
-results in a reduction in the production of steroid hormones, including DHEA
special side effects of abiraterone acetate
hypokalemia
hypertension
fluid overload
due to hyperaldosteronism: since pathway is shunted away from cortisol and DHEA, more aldosterone is made from the pathway
docetaxel mechanism
microtubule inhibitor
side effects of docetaxel
vomiting, diarrhea, constipation, and fatigue
how long after failure of first line therapy does a typical pt survive
10-20 yrs
progressive prostate cancer
bed bound >50% of the time
pain from osseous mets
neuro symptoms from spinal cord compression
renal failure from local growth causing ureteral obstruction
