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 |
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) |
Metastatic? | Castrate Resistant? | Workup | Treatments | Monitoring |
---|---|---|---|---|
No | No | PSAdt CT/MR Bone scan Consider PET |
Observation 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 |
iADT/cADT XRT + ADT (if low volume) Abiraterone + ADT Apalutamide/Enzalutamide + ADT Docetaxel + ADT (if high volume) |
|
No | Yes | Calculate PSAdt (cutoff ≤ 10mo) CT/MR Bone scan |
observation or ADT (if PSAdt > 10mo) Apalutamide/Enzalutamide/Darolutamide + ADT (if PSAdt ≤ 10mo) |
|
Yes | Yes | PSA, T, LDH, Hgb, AlkPhos CT/MR 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 |