Prostate Cancer

Screening

Screening considerations

Age-specific recommendations

Elevated PSA differential

PSA density

Probability of cancer diagnosis based on pre-biopsy PSA and DRE, from Campbell's

Prostate Biopsy

Recommendations

Risks of biopsy

Prostate MRI

Biopsy findings besides cancer

Prostate Cancer AUA Risk Classifications

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)

*Indications/Notes for Further Staging after Diagnosis

Active Surveillance/Watchful Waiting

Active Surveillance

Active Surveillance Protocols

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

Watchful Waiting

Focal Therapies

Basis for Focal Therapy as Treatment

Therapy options

Surgery (RALP) vs Radiation (XRT)

Considerations

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

Locally advanced disease (T3-T4)

Surgery

Surgical considerations

MSK nomograms

Specific surgical risks for counseling

Radiation (XRT)

General XRT options and terms

Risk-Based Options

Risks, Side Effects, and Other Considerations

Biochemical Recurrence

Considerations

After RALP

After XRT

PSA rise after RALP + XRT (no further local treatment options)

Androgen Deprivation Therapies (ADT)

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

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

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
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

Initial management of metastatic disease

Follow Up

Post-RALP

Post-XRT

Post-ADT

Metastatic disease

References: