Prostate cancer Flashcards
Epidemiology
Most common cancer in men in the US
Lung cancer is the #1 killer in both men/women
Prostate cancer is #2 killer
Pathogenesis
Hormonal: increased exposure to DHT
Androgen receptor: alterations in androgen receptor
Pathophysiology
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
History of disease
Indolent, slow growing disease
Spreads via lymphatics and hematogenous
Metastasis: BONE, liver, lung
Risk factors
Age–> increase exposure to DHT
Race–> more common in AA, less common in Asians
Family history–> increased if first degree relative has it
Signs/symptoms
Asymptomatic in early disease
Urinary abnormalities, impotence, edema, weight loos, anemia
Screening
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
When to start screening?
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
Prevention
Finasteride for 7 years
Diagnosis
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
Localized
early stage
Metastatic
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
Radiation
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
Androgen Deprivation Therapy
Goal: < 50 ng/mL after 1 month of therapy
Treatment: LHRH agonist +/- anti-androgen or orchiectomy
Leuprolide, -relin
SE: Gynecomastia, hot flashes, sexual dysfunction
Acute tumor flare in metastatic setting
Osteoporosis, fracture, increased risk for diabetes and CV events
Relugolix
oral
used for extensive CV events
-lutamide
androgen receptor antagonist
start 1 week prior to GnRH agonist for a total of 1 month
BICALUTAMIDE IS MOST COMMONLY USED
M0HSPC
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
M0CRPC
Diagnostics: PSA is continuing to increase on ADT and no distant metastasis
Continue ADT + Androgen receptor antagonist
M1HSPC
Diagnostics:
-Low volume–> few metastasis
-High volume–> multiple metastasis
M1CRPC
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
Enzalutamide
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)
Apalutamide
Drug interactions: CYP3A4 AND CYP2C8 substrate
SE: Seizures, fatigue, falls, diarrhea, HTN, increases cholesterol, glucose, triglycerides, TSH levels
Darolutamide
Drug interactions: CYP3A4 substrate
SE: Less seizures, falls, fractures, weight loss
Fatigue, diarrhea, musculoskeletal pain, HTN, rash, anemia
TAKE WITH FOOD
Low volume
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
High volume
ADT + Docetaxel OR ADT + Androgen receptor antagonist + Docetaxel
Use in: Visceral metastasis, 4 or more bone metastasis, one metastasis beyond pelvis vertebral column
