Lecture 12 - Prostate Cancer Flashcards
(48 cards)
Prostate cancer is the most common cancer in
men
2nd most common cause of cancer related death in men
1 in 8 men will be diagnosed with prostate cancer
Etiology/pathogenesis
hormonal: testosterone is a growth signal to the prostate, most risk factors associated with prostate cancer are related to increased exposure to testosterone
androgen receptor: alterations in androgen receptor
Risk factors
increased age, more common in african-americans, family history, diet (high fat intake), vitamin E, selenium, soy, and lycopenes may protect, textile or industrial workers, long-term vasectomy
Pathophysiology
urethra passes through the prostate and prostatic hypertrophy may compress the urethra - increased frequency, inability ot start and stop uring flow, dysuria, hematuria, nocturia, incomplete bladder emptying and dribbling
Signs and symptoms
asymptomatic with early disease - can tell from elevated PSA levels
advanced disease: alterations in urinary habits, impotence, lower extremity edema, weight loss, anemia
Diagnosis
physical exam, PSA level, transrectal ultrasound, serum chemistries, bone scane, CT/MRI is suspect metastatic disease
biopsy of prostate
histology: adenocarcinoma
Pathology
grading: gleason score (2-10)
scores assigned to primary and secondary growth patterns and then added together
scores of 2-4 are slow growing, well differentiated; scores of 8-10 are aggressive, poorly differentiated
higher the score, higher the risk of extracapsular spread
Prostate specific antigen
liquefies seminal secretions and increases with disorders of prostate
normal range is 0-4 ng/mL; >4 ng/mL requires evaluation; >10 ng/mL highly suspicious for malignancy
PSA velocity: >0.75 ng/mL rise per year suspicious for malignancy
Treatment overview
options: localized therapy, metastatic disease - m0HSPC, m0CRPC, m1HSPC, m1CRPC
m1 = metastatic
m0 = non-metastatic (PSA only)
HSPC = hormone sensitive prostate cancer
CRPC = castrate resistant prostate cancer
Treatment: localized - obervation
observation: monitor course of disease with expectation to deliver palliative therapy for development of sx or a change in exam or PSA that suggests sx are imminent
PSA + DRE every 6 mo
advantage: avoids immediate morbidity associated with tx
disadvantage: risk fo disease complications such as urinary retention or fractures
Treatment: localized - active surveillance
based on premise that prostate cancer is a benign and indolent disease
active monitoring of disease, if cancer noted to progress, will initiate potentially curative therapy
monitor PSA, DRE, and sx; treatment initiated with rising PSA or development of sx
advantages: 2/3 of pts will avoid therapy, avoid possible SEs, QOL less affected
disadvantages: 1/3 of pts may require tx, periodic f/u and test/biopsies may be necessary
Treatment: localized - radiation therapy
external beam vs brachytherapy
reasonable alternative to pts not eligible for surgery
complications: bladder and/or rectal sx, ED, radiation proctitis
give adjuvant ADT if intermediate or poor risk
Locally advanced/high risk
androgen deprivation therapy (ADT) in combo with external beam radiation therapy (EBRT) improved overall survival
start ADT prior to radiation and then continue ADT during radiation and for 1-3 years after
Treatment: localized - radical prostatectomy + PLND
definitive curative therapy; survival with surgery ~85% at 10 years
complications: early mortality, bladder contracture, incontinence, impotence
follow with ADT therapy
Androgen deprivation therapy
goal is to induce castrate levels of testosterone: goal level = <50 ng/dL after 1 month of therapy
surgically: orchiectomy; medically: LHRH agonists
ADT: LHRH agonist +/- anti-androgen or orchiectomy
antiandrogens: blocks androgen receptors and inhibits androgen uptake and binding in target tissues - bicalutamide, nilutamide, flutamide, abiraterone, enzalutamide
LHRH agonists
reversible and is as effective as orchiectomy
leuoprolide, goserelin, triptorelin, histerelin
LHRH antagonist - oral: relugolix - has less CV events (if pt has extensive cardiac history use this!)
LHRH agonsit toxicities
acute: tumor flare, gynecomastia, hot flashes, ED, edema
long-term: osteoporosis, fracture, obesity, insuling resistance, changes in lipids, increased risk of diabetes and CV events
Anti-androgens
flutamide
bicalutamide
nilutamide
these help prevent tumor flare
use these in combo with LHRH in metastatic setting
Metastatic prostate cancer
goals of therapy - palliation of disease
suppress testosterone production (<50 ng/dL)
need to determine whether this is a PSA recurrence or overt metastatic disease
Metastatic disease: m0HSPC
if only PSA recurrence, may delay start of ADT
if pt experiences a rapid PSA velocity or short PSA doubling time (< 6 mo) and has long-life expectancy: consider ADT
orchiectomy (removal of testes) - immediate drop in testosterone levels; SE = impotence and hot flashes
Metastatic: LHRH agonists
risk of disease flare in 1st weeks of therapy due to initial release of testosterone - add anti-androgen to prevent disease flare
sx of flare = bone pain or increased urinary sx
Intermittent ADT: m0HSPC
can start on LHRH agonist alone or with oral ADT
when PSA level has returned to pre-specified baseline, androgen suppression is d/c’d
PSA is monitored while pt off therapy and then androgen ablation therapy is restarted at pre-defined PSA
men with biochemical failure only can consider intermittent therapy
advantages: decreased cost and SEs (less CV evetns and fractures)
m0CRPC
is PSA still increasing and not responding to ADT and no distant metastasis found on scane, consider m0CRPC
1. continue ADT (usually LHRH agonist)
2. add on one of the following: enzalutamide, apalutamide, darolutamide
abiraterone not indicated in M0 setting!
Enzalutamide
blocks androgen binding and translocation of androgen receptor
avoid CYP2C8 inhibitors
decreases serum conc of warfarin; caution use in pts with seizure history (lowers seizure threshold)
toxicities: fatigue, seizures, falls, weakness, diarrhea, hot flashes, musculoskeletal pain, HA, HTN
