Prostate Cancer Flashcards
The most commonly diagnosed cancer for Men
Prostate Cancer
Treatment Plan for Prostate Cancer
Localized prostate cancer can be cured by surgery
or radiation therapy, but advanced prostate cancer
is not yet curable.
Risk Factors: Age Race Genetics Mutations occupational Diet Decreased Intake
Age:More than 70% of cases are diagnosed in men greater than 65 years old.
Race: African Americans have higher incidence and death rate.
Genetic Familial prostate cancer is inherited in an autosomal dominant manner.
Mutations in p53, Rb, E-cahedrin, a-catenin, androgen receptor,,microsatellite instability. Candidate prostate cancer gene locus identified on chromosome 1.
Occupational: Increased risk associated with cadmium exposure.
Diet: Increased risk associated with high-meat and high-fat diets.
Decreased intake of 1, 25-dihydroxyvitamin D, vitamin E, lycopene, and bcarotene increases risk.
Is Prostate Cancer Hormonal?
Hormonal Does not occur in eunuchs. Low incidence in cirrhotic patients
(why?). Up to 80% are hormonally dependent. African-Americans have 15%
increased testosterone. Japanese have decreased 5-a-reductase activities.
Polymorphic expression of the androgen receptor.
Currently, the most promising agent for the prevention of prostate cancer is
finasteride, a 5-α-reductase inhibitor
used for BPH.
Other agents, including selenium, vitamin E, lycopene,
green tea, nonsteriodal anti-inflammatory agents,
isoflavones, and statins, are under investigsation for
prostate cancer and show promise.
Screening for Prostate
1-Digital rectal examination (DRE).
2- Prostate specific antigen (PSA)
Pathophysiology Prostate Cancer
The growth and development of the prostate is
under control of androgens, and it is well known
that men who undergo castration prior to
puberty do not develop prostate cancer.
Antiandrogens inhibit the formation of the DHTreceptor complex and thereby interfere with
androgen-mediated action at the cellular level.
Localized Disease
Advanced Disease
Asymptomatic. Locally Invasive Disease • Ureteral dysfunction, frequency, hesitancy, and dribbling • Impotence. Advanced Disease: • Back pain • Cord compression • Lower extremity edema • Pathologic fractures • Anemia • Weight loss
Prostate Therapy
Androgen deprivation for 2 years
greater than 20 ng/mL and RT or RT or RP
What’s Expectant Management
observation or watchful waiting, involves monitoring the course of disease and initiating treatement if the cancer progresses or the patient becomes symptomatic.
Orchiectomy:
Bilateral orchiectomy, or removal of the testes, rapidly
reduces circulating androgens to castrate levels
(androstenedione less than 50 ng/mL, 1.7 nmol/L).
Radiation common methods:
The two commonly used methods for
radiation therapy are external-beam
radiotherapy and brachytherapy.
Complications from radical prostatectomy
include
blood loss, stricture formation,
incontinence, lymphocele, fistula
formation, anesthetic risk, and impotence
LHRH agonists MOA
Types of Drugs
LHRH agonists are a reversible method of androgen
ablation and are as effective as orchiectomy in
treating prostate cancer. Currently available LHRH
agonists include leuprolide, leuprolide depot,
leuprolide implant, and goserelin acetate implant.
The most common adverse effects reported with LHRH
agonist therapy include
a disease flare-up during the
first week of therapy, hot flashes, erectile impotence,
decreased libido, and injection-site reactions.
LHRH antagonists -
MOA
Treatment
These drugs work in a slightly different way from the
LHRH agonists, but they lower testosterone levels more quickly and don’t cause tumor flare like the LHRH agonists do.
Treatment with these drugs can also be considered a form of medical castration.
LHRH antagonists drugs-
Degarelix (Firmagon) is given as a monthly injection under the skin. Some men may notice problems at the injection site (pain, redness, and swelling). Relugolix (Orgovyx) is taken as pills, once a day, so it might
allow for less frequent office visits.
Antiandrogens Drugs:
Three antiandrogens, flutamide, bicalutamide, and
nilutamide,
Why are androgens used/ not used
antiandrogens is less effective than LHRH
agonist therapy.
Objective responses are manifested as decreased
bone pain, decreased prostate size, decreased
PSA, and/or improved performance state
Antiadrogens Side effects
Gynecomastia, Hot flushes, Gastrointestinal disturbances (diarrhea)
Combined Hormonal blockade
The rationale for combination hormonal therapy is to
interfere with multiple hormonal pathways to completely eliminate androgen action.
Relapse is usually after 2-4 years
Estrogens, are they used- why or why not
DES was once a mainstay of prostate cancer therapy. While very effective in androgen ablation, DES-treated patients experienced increased cardiovascular mortality
Second-line therapy for whom
Patients for their initial therapy has progressed
Types of second-line therapy
Supportive care, chemotherapy, or local radiotherapy can be used in
patients who have failed all forms of androgen-ablation
manipulations because these patients are considered to have
androgen-independent disease.
Whats added to Androgen for a better response
aminoglutethimide, at the time that androgens are withdrawn may produce a better response than androgen withdrawal alone.
Androgen synthesis inhibitors, such as aminoglutethimide and ketoconazole, can provide symptomatic relief for a short time in
approximately 50% of patients with progressive disease despite previous androgen-ablation therapy.
