Prostate cancer

Question 1

Epidemiology

Answer 1

Most common cancer in men in the US

Lung cancer is the #1 killer in both men/women

Prostate cancer is #2 killer

Question 2

Pathogenesis

Answer 2

Hormonal: increased exposure to DHT

Androgen receptor: alterations in androgen receptor

Question 3

Pathophysiology

Answer 3

Prostate is located anterior to the urethra and inferior to the bladder

Urethra passes through the prostate and hypertrophy of the prostate can compress the urethra

Increased frequency, urinary incontinence, dysuria, hematuria, nocturia

Question 4

History of disease

Answer 4

Indolent, slow growing disease

Spreads via lymphatics and hematogenous

Metastasis: BONE, liver, lung

Question 5

Risk factors

Answer 5

Age–> increase exposure to DHT

Race–> more common in AA, less common in Asians

Family history–> increased if first degree relative has it

Question 6

Signs/symptoms

Answer 6

Asymptomatic in early disease

Urinary abnormalities, impotence, edema, weight loos, anemia

Question 7

Screening

Answer 7

Digital rectal exam (DRE): presence of lumps, hardness, and inability to move the prostate

Prostate specific antigen (PSA)

Transrectal Ultrasonography (TRUS): indicated after an abnormal PSA or DRE

Question 8

When to start screening?

Answer 8

Start at the age of 50 (age 40 or 45 if high risk)

Annual: PSA level > 2.5 ng/mL

Every 2 years: PSA level < 2.5 ng/mL

Referral/evaluation: PSA level > 4 ng/mL

Question 9

Prevention

Answer 9

Finasteride for 7 years

Question 10

Diagnosis

Answer 10

PSA level

Normal: 0-4 ng/mL

Requires evaluation: > 4 ng/mL

Suspicious of malignancy:
> 10 ng/mL
> 0.75 ng/mL rise per year

Biopsy (2)–> 99% are adenocarcinomas

Gleason Score (total score of both biopsy)
2-4: slow-growing, differentiated
8-10: aggressive, poorly-differentiated

Question 11

Localized

Answer 11

early stage

Question 12

Metastatic

Answer 12

M0HSPC–>non-metastatic (PSA only ) + hormone sensitive

MOCRPC–> non-metastatic (PSA only) + castrate resistant

M1HSPC–> metastatic (on scans) + hormone sensitive
-Low volume
-High volume

M1CRPC–>metastatic (on scans) + castrate resistant

Question 13

Radiation

Answer 13

8-9 weeks

Type: External beam–>outside to prostate
Brachytherapy–> radioactive pellets implemented in/around prostate

Who–> patients not surgical candidates

Complications:
Bladder/rectal symptoms
ED
Radiation proctitis

May add adjuvant ADT if high risk patients (high gleason score)

Start ADT prior to radiation, during radiation, and 1-3 years after

Question 14

Androgen Deprivation Therapy

Answer 14

Goal: < 50 ng/mL after 1 month of therapy

Treatment: LHRH agonist +/- anti-androgen or orchiectomy

Question 15

Leuprolide, -relin

Answer 15

SE: Gynecomastia, hot flashes, sexual dysfunction

Acute tumor flare in metastatic setting

Osteoporosis, fracture, increased risk for diabetes and CV events

Question 16

Relugolix

Answer 16

oral

used for extensive CV events

Question 17

-lutamide

Answer 17

androgen receptor antagonist

start 1 week prior to GnRH agonist for a total of 1 month

BICALUTAMIDE IS MOST COMMONLY USED

Question 18

M0HSPC

Answer 18

Diagnostics:
-If PSA doubling time < 6 months: ADT
-If PSA doubling time > 6 months: observe

Treatment (1 of the following):
Orchiectomy (removal of testes)
GnRH Agonist + Androgen receptor antagonist (1 month only)

Intermittent ADT:
-GnRH Agonist +/- Androgen receptor antagonist is d/c when PSA level reaches < or equal to 4 ng/dL

-GnRH Agonist +/- Androgen receptor antagonist is restarted when PSA level reaches 10-20 ng/dL

Question 19

M0CRPC

Answer 19

Diagnostics: PSA is continuing to increase on ADT and no distant metastasis

Continue ADT + Androgen receptor antagonist

Question 20

M1HSPC

Answer 20

Diagnostics:
-Low volume–> few metastasis
-High volume–> multiple metastasis

Question 21

M1CRPC

Answer 21

ADT + any of the following

Docetaxel (1st line)
Cabazitaxel (2nd line)

Poor affinity for MDR–> effective in resistant tumors

SE: severe neutropenia and diarrhea

Sipuleucel-T

Radium 223–> DO NOT GIVE WITH CHEMO

Abiraterone + prednisone

Enzalutamide

BRCA: paribs
dMMR/MDI-H: pembrolizumab

Question 22

Enzalutamide

Answer 22

Drug interactions: CYP2C8 substrate, CYP3A4, 2C0, 2C19 inhibitor
Decreases concentration of warfarin

SE: Seizures, fatigue, weakness, falls, diarrhea, hot flashes, musculoskeletal pain, HTN, enzalutamide syndrome (foggy)

Question 23

Apalutamide

Answer 23

Drug interactions: CYP3A4 AND CYP2C8 substrate

SE: Seizures, fatigue, falls, diarrhea, HTN, increases cholesterol, glucose, triglycerides, TSH levels

Question 24

Darolutamide

Answer 24

Drug interactions: CYP3A4 substrate

SE: Less seizures, falls, fractures, weight loss

Fatigue, diarrhea, musculoskeletal pain, HTN, rash, anemia

TAKE WITH FOOD

Question 25

Low volume

Answer 25

Continue ADT + Androgen receptor antagonist

Abiraterone + prednisone
-Must be given with prednisone to prevent adrenal insufficiency

Drug interaction: CYP3A4 Substrate

SE: Fatigue, diarrhea, muscles aches, hot flashes, HTN, edema, increases TC and LFT, Afib, hypokalemia

TAKE WITHOUT FOOD

Enzalutamide
Apalutamide

Question 26

High volume

Answer 26

ADT + Docetaxel OR ADT + Androgen receptor antagonist + Docetaxel

Use in: Visceral metastasis, 4 or more bone metastasis, one metastasis beyond pelvis vertebral column