What is the treatment for stage 4 prostate cancer?

Treatment of Stage 4 Prostate Cancer

For stage 4 (metastatic) prostate cancer, androgen deprivation therapy (ADT) combined with androgen receptor pathway inhibitors (such as abiraterone or darolutamide) is the first-line treatment, with the addition of docetaxel chemotherapy for patients with extensive disease who are fit enough to receive it. 1, 2, 3

First-Line Systemic Therapy

Hormone-Sensitive Metastatic Disease (Initial Presentation)

Primary treatment consists of continuous ADT as the backbone, achieved through:

• Medical castration with LHRH analogs (goserelin, leuprolide) 4, 5, 3
• Surgical castration (bilateral orchiectomy) as an equally effective alternative 4

Combination therapy significantly improves survival over ADT alone:

• ADT + abiraterone + prednisone improves median overall survival from 36.5 months to 53.3 months (HR 0.66) 3
• Triplet therapy with ADT + docetaxel + darolutamide provides the greatest survival benefit (OS gain: 23.0 months, HR 0.68) for fit patients with de novo metastatic disease 2
• ADT + docetaxel should be added for patients with extensive metastatic burden, particularly those with multiple bone metastases or visceral metastases 1, 2, 3

Treatment Selection Algorithm

For newly diagnosed metastatic prostate cancer, choose based on:

• Extensive disease (multiple bone/visceral metastases) + fit for chemotherapy: Triplet therapy (ADT + docetaxel + darolutamide or abiraterone) 2, 3
• Limited metastatic disease or unfit for chemotherapy: ADT + androgen receptor pathway inhibitor (abiraterone, apalutamide, or enzalutamide) 1, 2
• Poor performance status or significant comorbidities: ADT monotherapy 4, 6

Castration-Resistant Metastatic Disease (CRPC)

When disease progresses despite castrate testosterone levels:

Asymptomatic or Mildly Symptomatic CRPC

• Abiraterone or enzalutamide as first-line agents 6, 7
• PARP inhibitors (olaparib) for patients with BRCA1/2 alterations after progression on androgen receptor axis inhibitors (HR 0.69 for OS) 2, 7

Symptomatic CRPC or After Novel Hormone Therapy Failure

• Docetaxel chemotherapy with prednisone for pain palliation and modest survival benefit 4, 7
• Cabazitaxel after docetaxel progression 7, 8
• Radium-223 for symptomatic bone metastases 1, 7
• Lutetium-177 PSMA-617 after progression on taxane and androgen receptor axis inhibitor, showing improved radiographic progression-free survival and overall survival 2, 7

Management of Specific Metastatic Sites

Brain Metastases (Uncommon but Important)

• Gadolinium-enhanced MRI for diagnosis 6
• Dexamethasone 4-8 mg/day for moderate symptoms, increasing to 16 mg/day for severe symptoms with mass effect 6
• Stereotactic radiosurgery (SRS) for 1-4 unresected brain metastases 6
• Surgical resection for large tumors with significant mass effect, symptomatic lesions refractory to steroids, or solitary accessible lesions 6

Bone Metastases

• Denosumab or zoledronic acid for skeletal-related event prevention 1
• External beam radiotherapy for painful bone metastases 4
• Radium-223 for symptomatic bone metastases in CRPC 1, 7

Locally Advanced Disease with Regional Nodes (N1M0)

For stage 4 disease limited to regional lymph nodes without distant metastases:

• Standard hormonal therapy (ADT) is recommended 4
• Consider radiotherapy + long-term ADT (at least 2 years) for locally advanced disease with nodal involvement 4

Critical Treatment Principles

ADT Administration Details

• LHRH analogs must be accompanied by an antiandrogen for the first 4 weeks to prevent testosterone flare 4
• No proven benefit for continuing total androgen blockade beyond 4 weeks 4
• Continuous ADT is superior to intermittent therapy for metastatic disease 6

Common Pitfalls to Avoid

• Do not use pure anti-androgens as monotherapy—they are associated with poorer outcomes compared to watchful waiting 4
• Do not delay chemotherapy in extensive disease—early addition of docetaxel to ADT improves survival significantly 2, 3
• Do not withhold treatment from symptomatic patients—symptomatic patients should not be denied treatment regardless of disease extent 4
• Prevent gynecomastia prophylactically with breast irradiation (8-15 Gy in 1-3 fractions) given 1-2 weeks before initiating antiandrogen therapy 4

Monitoring During Treatment

• PSA levels should be monitored regularly to assess treatment response 4
• Digital rectal examination every 6 months 4
• Imaging as clinically indicated for symptomatic progression 4

Emerging Therapies

• Bispecific T-cell engagers (BiTE) are under investigation but not yet standard of care 7
• Clinical trial participation is strongly encouraged given the rapidly evolving treatment landscape 2