Prostate Cancer

Question 1

Risk factors

Answer 1

Increasing age (65-74)
Family history
African american
BRCA-2 mutations and Lynch syndrome

Question 2

Localized disease presentation

Answer 2

asymptomatic

Question 3

Locally invasive disease presentation

Answer 3

ureteral dysfunction
urinary frequency
urinary hesitancy
dribbling or decreased urinary stream
incomplete bladder emptying

Question 4

advanced disease presentation

Answer 4

back pain
cord compression
lower-extremity edema
pathologic fractures
anemia
weight loss

Question 5

prognostic factors

Answer 5

PSA
tumor size and extent of primary tumor
histologic grade- gleason score

Question 6

PSA

Answer 6

can be lowered by 5alpha-reductase inhibitors (finasteride/dutasteride)
increased in BPH
normal rand <4ng/mL- some patients with those levels develop prostate cancer
PSA velocity may be another predictor (0.35ng/dL/year)

Question 7

Gleason score

Answer 7

describes how cancer cells look under a microscope
Scores range from 1-5
2 most common patterns are added together
Low <6
High >7 (8 or greater)

Question 8

Factors to consider for treatment

Answer 8

comorbidities
symptoms
recurrence risk- gleason score, metastatic, high risk
life expectancy
disease stage
-surgery 10 yr life expectancy and tumor confined to prostate

Question 9

LHRH agonists

Answer 9

*Goserelin, leuprolide, triptorelin, histrelin
Acute ADEs: tumore flare, hot flashes, erectile dysfunction, edema, gynecomastia, injection site reaction
Long-term: osteoporosis, clinical fracture, obesity, insulin resistance, increased risk of diabetes, CV events, hyperlipidemia

Increased initial testosterone production- resolves after 2 weeks
-start 1st gen antiandrogen and continue for 2-4 weeks to mitigate tumore flare
Baseline bone mineral density test
-calcium and vitamin D supplementation

Question 10

LHRH antagonist

Answer 10

*Degarelix and Relugolix
Testosterone drops much faster
less flexibility in dosing schedule (q month),high cost

Question 11

antiandrogens

Answer 11

1st gen- bicalutamide, flutamide, nilutamide
diarrhea, gynecomastia, elevated LFTs, hot flashes
Monitoring: LFTs monthly x4 (then periodically) serum testosterone, PSA, pulmonary function (nilutamide)

2nd gen
apalutamide (M0)
enzalutamide (M0 and M1)
darolutamide (M0)

Question 12

Castration sensitive prostate cancer

Answer 12

ADT + abiraterone or apalutamide or enzalutamide

ADT wit docetaxel x 6 cycles + abiraterone or darolutamide
-high volume castration sensitive

Question 13

Nonmetastatic CRPC

Answer 13

PSADT >10 months
-monitor or
-other secondary hormone therapy

PSADT <10 months
1) apalutamide
2)enzalutamide
3) darolutamide
4) other secondary hormone therapy

Question 14

other secondary hormone therapy

Answer 14

first generation antiandrogen (nilutamide, flutamide, or bicalutamide)
Corticosteroids (hydrocortisone, prednisone, or dexamethasone)
Antiandrogen withdrawal
ketoconazole plus hyddrocortisone

Question 15

apalutamide

Answer 15

androgen receptor inhibitor - decreased proliferation of tumor cells and increased apoptosis
falls and fractures
seizure!- permanently discontinue

Question 16

darolutamide

Answer 16

androgen receptor inhibitor
fatigue, HTN, rash
No sezure!

Question 17

enzalutamide

Answer 17

androgen receptor signaling inhibitor
diarrhea, fatigue, edema
increased risk of seizures

Question 18

M1 CRPC treatment options no prior ADT or docetaxel

Answer 18

Abiraterone
Docetaxel
enzalutamide

Question 19

M1 CRPC treatment options prior ADT no prior docetaxel

Answer 19

Docetaxel
Olaparib or rucaparib for BRCA mutation

Question 20

M1 CRPC treatment options prior docetaxel no prior ADT

Answer 20

abiraterone
cabazetaxel
enzalutamide

Question 21

M1 CRPC treatment options prior docetaxel and ADT

Answer 21

cabazitaxel
docetaxel rechallenge

Question 22

abiraterone

Answer 22

inhibits formation of testosterone precursors and androstenedione
*give with steroids to minimize signs of mineralcorticoid excess from treatment
Monitor: LFTs, potassium and phosphate levels, blood pressure on monthly basis

Question 23

olaparib

Answer 23

inhibits PARP enzymes- which aid in DNA repair
PARP inhibitors have been shown to double your risk of secondary cancer - MDS or AML
Monitor: blood counts, serum creatinine, and signs and symptoms of pneumonitis

Question 24

radium-223

Answer 24

antitumor effect on bone metasteses
useful for symptomatic bone metastases and no visceral metastases prior to and after docetaxel therapy
NOT used in combo with chemo
Peripheral edema, nausea, myelosuppression

Question 25

Sipuleucel-T

Answer 25

Dendritic cell vaccine designed to enhance immune T cell response to prostatic acid phosphatase
-prepared from peripheral blood mononuclear cells obtained by leukapheresis
-activated cells then infused back 3 days after harvesting
given at 2 week intervals for 3 total doses

infusion reaction, chills, fever, fatigue, headache

Question 26

Other 2nd line therapies

Answer 26

pembrolizumab- MSI-H, dMMR, TMB>10
Radium-223 for bone metastases
Olaparib for HRR
Rucaparib for BRCAm
Lutetium Lu177 vipivotide tetraxetan based on PSMA

Question 27

cabazitaxel

Answer 27

activity in docetaxel resistance
febrile neutropenia, hypersensitivity reaction, mucositis, edema

Question 28

lutetium Lu 177 vipivotide tetraxetan

Answer 28

beta-emitting radiopharmaceutical that selectively binds to PSMA receptors on prostate cancer cells
PSMA-positive M1 CRPC
fatigue, dry mouth, nausea, and myelosuppression

Question 29

Supportive care

Answer 29

ADT
-baseline and yearly DEXA scans
-calcium 1000-1200mg daily and vtamin 400-800IU daily

Bone metastases modifying agents (prevent skeletal related events and possible antitumor effect)
-zoledronic acid
-denosumab

General osteoporosis/ bone loss, different dosing and formulation used
treatment of androgen deprivation induced bone los: denosumab
osteoporosis: zoledronic acid IV once a year