Risk Group | Grade Group | Clinical Stage | PSA | # Cores Positive | % Core Involvement | PSA Density | Further Workup | Treatment Recommendations | Metastatic risk on surveillance |
---|---|---|---|---|---|---|---|---|---|
Very Low | GG1 | cT1-T2a | < 10 | < 1/3 | < 50% | < 0.15 | none | Active Surveillance | < 1% @ 10-15yrs |
Low | - | Active Surveillance (unless high risk for progression) |
~3% @ 10-15yrs | ||||||
Intermediate Favorable | GG1 GG2 |
cT2b-c | 10-20 <10 |
* | RALP +/- PLND XRT +/- ADT |
> 10-20% @ 15yrs | |||
Intermediate Unfavorable | GG2 GG3 |
cT2b-c | 10-20 < 20 |
* | RALP + PLND XRT w/o ADT |
||||
High | GG4-5 | cT3-T4 | > 20 | CT +/- MR bone scan Consider genetic testing |
RALP + PLND XRT + ADT ADT only (palliative option) |
Guideline | PSA | DRE | MRI | Biopsy |
---|---|---|---|---|
AUA | q3-6mo | q12mo | Unclear role | Repeat within 6-12mo Then q3-5yrs |
ASCO | ||||
Cancer Care Ontario | If disconnect between pathology and clinical findings | |||
NICE | q3-4mo, adjust per kinetics | At enrollment |
Surgery | XRT | |
---|---|---|
Benefits | Removes all cancerous tissue Confirms diagnosis for upstaging Salvage XRT "easier" than salvage surgery |
No incisions/surgery, no recovery needed No anesthetic risk |
Risks | Immediate incontinence, 5-10% persistence at 1yr Immediate erectile dysfunction (with improvement over time) Usual surgical risks |
Salvage RALP has high complication rate Worsens baseline LUTS Hematuria Acute/delayed GI toxicity Secondary malignancy |
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 (50mg daily) Flutamide |
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 (160mg daily) Apalutamide (240mg daily) |
mCRPC | Both: rash, fatigue, diarrhea Enzalutamide: seizures (< 1%) Apalutamide: falls/fractures (12%), hypothyroid (8%) |
|
GnRH Inhibition | Agonists: leuprolide, goserelin Antagonists: degarelix, cetorelix |
Monotherapy or combination with other medications | T surge: occurs within 10-20 days, can cause symptom exacerbation if bone mets |
Androgen Synthesis Inhibitors | Abiraterone (1000mg daily) | CYP17 inhibitor | Treat with prednisone (5mg QD-BID) 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 | Microtubule assembly inhibitor | Febrile neutropenia (15%) Systemic symptoms (7%) GI symptoms (8%) |
Cabazitaxel | Used for mCRPC after docetaxel | Neutropenia | |
Sipuleucel-T | Immunotherapy | Improves survival without clinical/serologic/radiographic response | |
Radium-223 | 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 | PARP inhibitor | Anemia, nausea | |
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 |
ADT XRT + ADT (if low volume) Abiraterone + ADT Apalutamide/Enzalutamide + ADT Docetaxel + ADT |
|
No | Yes | Calculate PSAdt (cutoff ≤ 10mo) CT/MR Bone scan |
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 |