Prostate Cancer Flashcards
Prostate Cancer Clinical Presentation
Localized disease:
- asymptomatic
Locally invasive disease:
- ureteral dysfunction, urinary frq, urinary hesitancy, incomplete bladder emptying
Advanced disease:
- back pain, cord compression, lower extremity edema, pathologic fractures, anemia, weight loss
Prognostic factors
Prostate specific antigen (PSA)
- normal < 4
- >10 high risk
Tumor size
Histologic grade (Gleason Score)
- 2 to 4: less aggressive
- 7 to 10: more aggressive
When you see this card review the local disease initial therapies chart
Do it, Bitch >:/
Androgen Deprivation Therapy
Gold standard treatment for advanced prostate cancer
- Surgical castration (not common anymore)
- Medical castration: LHRH agonist +/- antiandrogen, OR LHRH antagonist
LHRH agonists
- reversible method of androgen ablation
- goal serum testosterone < 50 ng/dL one month after starting therapy
Agents: - Goserelin (Zoladex)
- Leuprolide (Lupron IM, Eligard SQ)
LHRH agonist acute ADE
tumor flare
hot flashes
erectile dysfunction
edema
gynecomastia
injection site reaction
LHRH agonist chronic ADE
Osteoporosis
clinical fracture
obesity
insulin resistance
increased risk of diabetes
CV events
hyperlipidemia
LHRH agonists counseling points
Initial tumor flare caused by LH/FSH surge
- presents clinically as bone pain or increased urinary sx
- resolves after about 2 weeks
- management: first gen antiandrogen before the administration of LHRH agonist and continuing for 2-4 weeks
Baseline bone mineral density test before starting long term ADT
- calcium and Vit D supplementation
LHRH antagonists
Agents:
- degarelix (Firmagon)
- relugolix (Orgovyx)
Faster effects than LHRH agonists
Antiandrogens
MOA: inhibit androgen uptake and/or binding of androgen to target tissues
First Gen:
- Biculatamide
- Flutamide
- Nilutamide
- ADE: diarrhea, gynecomastia, inc LFTs, hot flashes
2nd gen: (more potent, preferred)
- Apalutamide (M0)
- Enzalutamide (M0 or M1)
- Darolutamide (M0)
Combined Androgen Blockade
LHRH agonist or antagonist + antiandrogen
higher risk of ADE
Controversial: can be used as an initial therapy or add after several months if androgen ablation is incomplete (testosterone not < 50)
Castration Sensitive Prostate Cancer
ADT + Abiraterone or Apalutamide or Enzalutamide
ADT w/ Docetaxel x6 cycles + Abiraterone or Darolutamide
- good for high volume castration sensitive metastatic prostate cancer
high volume = visceral metastases, and/or 4 bone metastases with at least 1 metastases beyond pelvis
M0 Castration Resistant Prostate Cancer (CRPC) treatment
if PSADT > 10 months:
- monitor (preferred)
- other secondary hormone therapy
if PSADT </= 10 months:
- Apalutamide
- Enzalutamide
- Darolutamide
- other secondary hormone therapy
Secondary Hormone Therapies
2nd gen antiandrogen:
- Apalutamide
- Darolutamide
- Enzalutamide
Androgen metabolism inhibitor:
- abiraterone + prednisone or methylprednisone (M1 only)
Other secondary hormone therapy:
- First gen antiandrogen (nilutamide, flutamide, or bicalutamide)
- corticosteroids
- antiandrogen withdrawal
- ketoconazole + hydrocortisone
Apalutamide (Erleada)
MOA: nonsteroidal androgen receptor inhibitor
ADE: fatigue, HTN, rash, diarrhea, nausea, arthralgias, fracture risk, peripheral edema, seizure
CI: seizure hx, DC if seizure occurs
Darolutamide (Nubeqa)
MOA: competitive androgen receptor inhibitor
ADE: fatigue, HTN, Rash
Pearls:
- take with food
- no increase in seizure risk
Enzalutamide (Xtandi)
MOA: pure androgen receptor signaling inhibitor
ADE: diarrhea, fatigue, HA, myalgia, edema, seizures
M1 CRPC treatment: No prior Docetaxel or novel hormone therapy
Preferred:
- Abiraterone
- Docetaxel
- Enzalutamide
Other:
- Radium-233 (for symptomatic bone metastases)
- Sipuleucel-T
- other secondary hormone therapy
M1 CRPC treatment: prior novel hormone therapy / no prior docetaxel
Preferred:
- docetaxel
Other:
- cabizataxel/carboplatin
- Olaparib (for HRRm)
- Rucaparib (for BCRA)
- Radium 223 (sx bone metastases)
- Sipuleucel-T
- abiraterone +/- dexamethasone
- other secondary hormone therapy
M1 CRPC treatment: prior docetaxel / no prior novel hormone therapy
Preferred:
- Abiraterone
- Cabazitaxel
- Enzalutamide
Other
- Cabazitaxel/Carboplatin
- Mitoxantrone (for sx patients who can’t tolerate other therapies)
- Radium 223 (sx bone metastases)
- Sipuleucel-T
- other secondary hormone therapy
M1 CRPC treatment: prior docetaxel and novel hormone therapy
Preferred:
- Cabazitaxel
- Docetaxel rechallenge
Other:
- Lutetium Lu 177 (for PSMA positive metastases)
- Cabazitaxel/carboplatin
= Olaparib for HRRm
- Mitaxantron for palliation
- Rucaparib for BRCA
- Radium223 for sx bone metastases
- Pembrolizumab
- Abiraterone
- Enzalutamide
- Other secondary hormone therapy
Docetaxel (Taxotere)
MOA: inhibition of DNA, RNA, and protein synthesis
ADE: myelosuppression, alopecia, edema, peripheral neuropathy, hypersensitivity rxn
Caution with hepatic impairment, avoid if:
- Tbili > ULN
- AST +/- ALT > 1.5x ULN AND alk phos > 2.5x ULN
Pearls: co-administer with prednisone
Abiraterone (Zytiga, Yonsa)
MOA: inhibits formation of the testosterone precursors DHEA and androstenedione
ADE: diarrhea, edema, hypoK, HTN, hepatotoxicity, hypertriglyceridemia
Pearls: admin with prednisone or methylprednisolone)
- Zytiga should be given on empty stomach (1hr before or 2 hrs after food)
- Yonsa may be administered with or without food
Radium-223 (Xofigo)
MOA: radiopharmaceutical -> breaks DNA
ADE: peripheral edema, nausea, myelosuppression
Pearls:
- do not give with chemo
- used for symptomatic bone metastases
Cabazitaxel (Jevtana)
MOA: microtubule inhibitor
ADE: febrile neutropenia, hypersensitivity rxn, mucositis, edema
Lu-177-PSMA-617 (Pluvicto)
beta-emitting radiopharmaceutical that selectively binds to PSMA receptors on prostate cancer cells
Indicated for PSMA+ M1 CRPC
ADE: fatigue, dry mouth, nausea, myelosuppression
Prostate Cancer Supportive care
Screen for diabetes and CVD in all patients receiving ADT
Yearly bone mineral density monitoring
- Calcium 1000-1200 mg QD
- Vitamin D 400-800 IU daily
- androgen induced bone loss: Denosumab
- osteoporosis: Zoledronic acid
