Metastatic Prostate Cancer

Androgen Deprivation Therapy (ADT) and other drugs

Treatment Class Specific Treatment Uses Side Effects
Surgical Treatment Orchiectomy Castration within 6hrs Cosmetic perception
Less side effects than drugs
Androgen Receptor Antagonist First Generation:
Bicalutamide (Casodex, 50mg daily)
Flutamide (Eulexin)
Nilutamide (Nilandron)
Prevent T surge with initiation of GnRH agonists Inadequate as monotherapy
T converted to E, gynecomastia
Impotency (80%)
Hepatitis (monitor LFTs)
Withdrawal can decrease PSA due to mutation causing drug to act as an agonist
Second Generation
Enzalutamide (Xtandi, 160mg daily)
Apalutamide (Erleada, 240mg daily)
Darolutamide (Nubeqa, 600mg BID)
mCRPC Both: rash, fatigue, diarrhea
Enzalutamide: seizures (< 1%)
Apalutamide: falls/fractures (12%), hypothyroid (8%)
GnRH Inhibition Agonists: leuprolide (Lupron/Eligard), goserelin (Zoladex)
Antagonists: degarelix (Firmagon), relugolix (Orgovyx)
Monotherapy or combination with other medications T surge: occurs within 10-20 days, can cause symptom exacerbation if bone mets
Androgen Synthesis Inhibitors Abiraterone (Zytiga, 1000mg daily) CYP17 inhibitor Treat with prednisone (5mg QD for CS, BID for CR) to prevent hypocortisolism
Ketoconazole (400mg TID) Blocks 17,20 desmolase
castration within 4hrs
Treat with hydrocortisone (5-20mg BID)
Gynecomastia, hepatitis
Non-ADT Treatments Docetaxel (Taxotere, q3wk) Microtubule assembly inhibitor Febrile neutropenia (15%)
Systemic symptoms (7%)
GI symptoms (8%)
Cabazitaxel (q3wk) Used for mCRPC after docetaxel Neutropenia
Sipuleucel-T (Provenge) Immunotherapy Improves survival without clinical/serologic/radiographic response
Radium-223 (Xofigo) a-emitting particle causing dsDNA breaks
Bone metastases without visceral metastases
Neutropenia (2%)
Thrombocytopenia (6%)
Do not give with abiraterone
PSA monitoring is not accurate
Olaparib (Lynparza, 300mg BID)
Rucaparib (Rubraca, 600mg BID)
PARP inhibitor Anemia, nausea, DVT (7%), MDS/AML (< 1.5%)
Pembrolizumab anti-PD1 monoclonal antibody Immunosuppresion side effects

When to Use Immediate ADT

Situation Immediate ADT?
Low risk, localized disease No benefit
Locally advanced Improves cancer-specific survival
No benefit in overall survival
Asymptomatic metastatic disease
Node-positive prior to primary therapy May provide benefit
Node-positive after surgery Improves overall survival
After biochemical recurrence, asymptomatic Not required, okay for intermittent ADT (set threshold)

General complications of ADT

Intermittent ADT

Survival on ADT

Metastatic Prostate Cancer

Defining Metastatic Disease

Treatment Recommendations for Metastatic and/or Castrate Resistant Prostate Cancer

Metastatic? Castrate Resistant? Workup Treatments Monitoring
No No PSAdt
Bone scan
Consider PET
iADT (PSA cutoff 4-10)
Clinical trials
PSA q3-6mo
Consider repeat imaging q6-12mo
Yes No CT/MR
Bone scan
PET (57% positive if PSA > 1)
Consider genetic testing
XRT + ADT (if low volume)
Abiraterone + ADT
Apalutamide/Enzalutamide + ADT
Docetaxel + ADT (if high volume)
No Yes Calculate PSAdt (cutoff ≤ 10mo)
Bone scan
observation or ADT (if PSAdt > 10mo)
Apalutamide/Enzalutamide/Darolutamide + ADT (if PSAdt ≤ 10mo)
Yes Yes PSA, T, LDH, Hgb, AlkPhos
Bone scan
Consider genetic testing
ADT + Abiraterone
ADT + Docetaxel
ADT + Enzalutamide
Sipuleucel-T (if asymptomatic or minimally symptomatic)
Radium-223 (if bony metastases only)
Cabazitaxel (if prior docetaxel)
Olaparib/Rucaparib (if germline mutation)
Carboplatin (if no germline mutation)
Pembrolizumab (if MMR mutations)
Annual imaging

Initial management of metastatic disease

Castrate resistant disease

Acute cord compression management