Monday
1) Describe epidemiology, etiology, and pathophysiology of prostate cancer
a. Most common male cancer, second most lethal
b. Risk factors are age, ethnicity (African American, because they have
more testosterone), family history (BRCA, first-degree relative), diet
(high fat, NOT smoking or alcohol)
c. Define Gleason Score
i. Measures differentiation of tumor
ii. 2 to 4 for well differentiated (low grade, good prognosis, grow
slowly)
iii. 5 to 6 for moderately differentiated
iv. 7 to 10 for poorly differentiated (high grade, poor prognosis,
grow rapidly)
v. Normal growth and differentiation of prostate depends on
androgens, specifically DHT
d. Define most common presentation of prostate cancer
i. Urinary hesitancy
ii. Retention
iii. Painful urination
iv. Hematuria
v. Erectile dysfunction
2) Define the general concepts of use of prostate specific antigen (PSA) and
digital rectal exam (DRE) for the screening and monitoring of prostate cancer
a. DRE
i. Specific but insensitive
ii. Poor compliance
iii. Little effect as a single screening method
iv. Start at 40-45, then annually at 50
b. PSA
i. Simple but low specificity
ii. May be falsely elevated in acute urinary retention, acute
prostatitis, prostatic ischemia or infarction, BPH
iii. PSA between 4.1 and 10 cannot distinguish between BPH and
prostate cancer. So not good alone for early detection.
iv. Many men have PSA within reference range with clinically
significant cancer
v. Helpful after diagnosis has been established
c. USPSTF recommends against screening
d. ACS recommends that they have the opportunity to screen
e. NCCN says enroll after though pros and cons
f. Confirm diagnosis by biopsy
3) Identify the risk factors linked to the development of prostate cancer
a. Lifetime exposure to testosterone
b. African American
c. Family history: first-degree relative, BRCA1 and 2
d. High fatty diet
e. Vitamin E
i. High dose, fat soluble
f. BPH, Smoking, Alcohol do NOT increase risk
4) List the factors that influence treatment selection for prostate cancer
a. Tumors can become anti-androgen refractory
b. PSA
c. 10-year survival
d. Stage A D2
e. Symptomatic/Asymptomatic
f. Gleason scale (differentiation)
g.
5) Compare and contrast treatment modalities for various stages of prostate
cancer
a. Active surveillance vs. observation
i. Observation is expectant management
1. Monitor disease (PSA q6months, DRE q12months, and
no more)
2. Treat if cancer progresses AND symptoms develop or are
eminent (PSA >100), will then convert to palliative ADT
3. Observation is preferred for low-risk and life expectancy <
10 years
ii. Active surveillance is watchful waiting
1. May involve surveillance prostate biopsies
2. Evidence of progression will prompt conversion to
potentially curative therapy
3. Active surveillance is preferred for men with very-low-risk
cancer and survival < 20 years.
iii. Dont do biopsies if observation of < 10 year life expectancy
b. ADT, systemic chemotherapy
i. Primary systemic therapy in advanced/metastatic disease or as
neo/adjuvant therapy with radiation in localized disease
ii. ADT is for intermediate-risk
iii. ADT combined with RT for high-risk
iv. ADT is gold standard for metastatic disease. Not used as
monotherapy in localized
v. ADT is NOT given with radical prostectomy, but IS given with
radiation therapy
vi. ADT includes:
1. LHRH agonist or antagonist (medical castration) and
bilateral orchiectomy (surgical castration) are equivalent.
2. Combined androgen blockade (castration + antiandrogen) has no benefit over castration alone
3. Anti-androgen should precede or be coadministered with
LHRH agonist for 7 days
4. Anti-androgen monotherapy is NOT recommended
5. Castration = bilateral orchiectomy
c. General principles of surgery and radiation (side effects/risks)
i. Surgery ADEs are blood loss, stricture formation, incontinence,
lymphocele, fistulas, anesthetic risk, and impotence.
ii. Radiation is cystitis, proctitis, hematuria, urinary retention,
penoscrotal edema, less impotence than surgery.
6)
7)
8)
9)
iii. Both have significant and immediate mortality compared with
expectant management.
d. OTHER
i. Early stage can use surgery (curative), radiation (curative), or
expectant management (this one may be preferred because
morbidity/mortality)
1. If less than 10-year survival can just do radiation or just
observation
2. If greater, can do observe, radiation, or surgery
(prostatectomy). Radiation and radical prostatectomy are
equivalent for localized cancer.
ii. Advanced stage mainstay is androgen deprivation therapy,
reduce testosterone to castrate levels, with either orchiectomy
or an LHRH agonist
iii. High risk of recurrence will receive androgen ablation for 2 to 3
years combined with radiation therapy.
iv. ADT with a LHRH agonist plus anti-androgen should be used
prior to surgery for locally advanced. ?
v. Treat bone metastasis
Discuss methods of androgen deprivation therapy (ADT)
a. LHRH
b. LHRH plus anti-androgen
c. Orchiectomy
d. All can be used for palliative in advanced advanced disease
Describe side effects associated with ADT and antiandrogen therapy
a. Androgen deprivation ADEs include cognitive impairment, mood
disturbances, and lack of initiative.
List mechanism of action of pharmacotherapy options for prostate cancer
Recognize which prostate cancer patient population receives systemic
chemotherapy
a. Systemic chemotherapy (docetaxel) is for symptomatic castrateresistant prostate cancer = symptomatic mCRPC. Docetaxel for
symptomatic or disease involving internal organs, such as liver. Her
slides just say symptomatic
b. Sipuleucel-T for asymptomatic (or minimally symptomatic) with a
rising PSA
i. Chills, pyrexia, and headache
ii. Immunotherapy
iii. Best if good performance status, life expectancy > 6 months
iv. No hepatic metastasis
v. No or minimal symptoms
c. Symptomatic visercal following docetaxel, use abiraterone acetate
d. Can use Cabazitaxel with either prednisone or enzalutamide (antiandrogen)
e. ADT and docetaxel should be given to metastatic disease
f. Abiraterone and Enzalutamide for metastatic castrate-resistant
prostate cancer (mCRPC), good alternatives to docetaxel
g. Chemotherapy is for mCRPC in general
Radiation = radical prostatectomy
LHRH agonist = bilateral orchiectomy
Class Notes
LH and FSH go to both Testes and directly to Prostate cells. Give ADT in intermediate
(with radiation), pair with all treatment options in high and above. Metastatic pair
ADT with chemo. Can observe very-low through intermediate, can active
surveillance very-low through low. Outcomes are worse with surgery. Can give
chemo if high-volume good performance status ADT-nave healthy patient. ADT
starts with N1 or intermediate, dont use intermittent in metastatic or in curative
therapy. Testosterone is pro-bone. Anti-androgen is NOT ADT*. IM ro SubQ
leuprolide. Abiraterone is given with PREDNISONE to prevent adrenal insufficiency,
Cyp17, fluid retention, hypokalemia. Cabazitaxel is second-line if docetaxel doesnt
work.
1) Identify signs and symptoms of prostate cancer
a. Most present as asymptomatic
b. Hesitancy, Frequency, Night time, Painful, Retention, Hematuria
c. Erectile dysfunction
2) Discuss the application of Gleason Scores
a. <6 is well differentiated
b. 7 = moderate
c. 8-10 = poorly differentiated
d. Tumor size, Gleason score, and PSA are used specifically in Risk of
Recurrence
3) Rationalize prostate cancer, non-pharmacologic treatment methods and their
side effects
a. Radiation causes less impotency, GI, incontinence, frequency, dysurea
b. Prostectomy causes impotency, blood loss
4) Describe treatment options for bladder cancer
a. Live mycobacterium to host cancer cells
i. Systemic absorption is rare
ii. Pour bleach
iii. Not within 48 hours of treatment. Use condom during treatment
and 6 weeks
iv. Women can use contraception
b. Treat BCG
5) Identify features of renal cancer
a. Clear cell is most common
b. Flank pain, hematuria, fatigue
