What are the treatments for prostate cancer?

Prostate Cancer Treatment Overview

Treatment for prostate cancer depends on disease stage and risk stratification, with options ranging from active surveillance for low-risk disease to combination systemic therapy for metastatic disease, prioritizing mortality reduction and quality of life preservation.

Risk-Stratified Treatment Approach

Low-Risk Localized Disease (T1-2a, Gleason ≤6, PSA <10 ng/mL)

Active surveillance is the preferred management strategy for low-risk prostate cancer rather than immediate intervention 1. This approach achieves 99% disease-specific survival at 8 years while avoiding treatment-related morbidity 2.

Monitoring protocol includes:

• PSA measurement every 6 months 1
• Digital rectal examination every 12 months 1
• Repeat prostate biopsy every 12 months 1
• First follow-up at 3 months to establish baseline 1

Intervention triggers:

• Gleason score upgrade to ≥7 on repeat biopsy 1
• PSA velocity >2.0 ng/mL/year 1
• Increased tumor volume (>3 cores positive or >50% involvement per core) 1

Low-Risk Treatment Options (When Intervention Required)

For patients requiring treatment, radical prostatectomy, external beam radiotherapy (minimum 70 Gy in 2.0 Gy fractions), and brachytherapy achieve similar long-term survival outcomes 2, 1. The 10-year survival rate is 90-94% with all treatment modalities 2.

Key treatment considerations:

• External beam radiotherapy should use conformal techniques with minimum target dose of 70 Gy 2
• Brachytherapy with permanent implants results in similar survival to radical prostatectomy with less chronic urinary symptoms and erectile dysfunction 2
• Radical prostatectomy significantly reduced disease-specific mortality (4.6% vs. 8.9% at median 6.2 years follow-up) compared to watchful waiting, though no difference in overall survival was observed 2

Intermediate and High-Risk Localized Disease (T2-T4)

Androgen suppression combined with external beam radiotherapy significantly improves local control, reduces disease progression, and improves overall survival 2.

Treatment protocol:

• Neoadjuvant LHRH agonist therapy for 4-6 months before radiotherapy 2
• Adjuvant hormonal therapy for minimum 6 months, ideally 2-3 years 2
• External beam radiotherapy with target dose ≥66 Gy in 1.8-2.0 Gy fractions over 6-7 weeks 2

Preventive measure: Breast irradiation (8-15 Gy in 1-3 fractions) should be given 1-2 weeks before antiandrogen therapy to prevent painful gynecomastia 2.

Metastatic Hormone-Sensitive Prostate Cancer

First-line treatment is triplet therapy combining ADT + docetaxel + darolutamide, which provides significant overall survival benefit (23.0 months OS gain, HR: 0.68) 3.

Alternative first-line regimens:

• ADT + docetaxel + abiraterone + prednisone for fit men with de novo metastatic disease, especially those with multiple bone metastases or visceral metastases 3
• ADT + novel hormone agents (abiraterone + prednisone, apalutamide, or enzalutamide) 3

Standard hormonal approach:

• Medical castration with LHRH analogs or surgical castration (orchiectomy) 2
• LHRH analogs should be accompanied with antiandrogen for 4 weeks to prevent disease flare 2
• No proven benefit for continuing total androgen blockade beyond 4 weeks 2

Castration-Resistant Prostate Cancer (CRPC)

Patients with CRPC should continue androgen suppression and receive sequential therapies based on disease burden and prior treatments 2.

Treatment sequence:

• Docetaxel 75 mg/m² every 3 weeks with prednisone 5 mg orally twice daily for symptomatic metastatic CRPC 4. This provides modest survival benefit and palliates pain 2, 5
• Olaparib (PARP inhibitor) after novel androgen receptor axis inhibitors for patients with BRCA1/2 alterations (improved OS: HR 0.69,95% CI 0.50-0.97) 3
• Lutetium-177 PSMA-617 combined with best standard of care for patients pretreated with at least one taxane and one novel androgen receptor axis inhibitor 3

Second-line hormonal therapies:

• Antiandrogens (cyprosterone acetate, flutamide, bicalutamide, nilutamide) 2
• Corticosteroids 2
• Progestins 2

Bone Metastases Management

For painful bone metastases:

• External beam radiotherapy using 1 × 8 Gy or 10 × 3 Gy fractionation with equal pain-reducing efficacy 2
• Radioisotope therapy (strontium-89 or samarium-153-EDTMP) 2
• Intravenous bisphosphonates (pamidronate) or denosumab for pain resistant to palliative radiotherapy 2

Post-Treatment Surveillance

Following radical prostatectomy:

• Serum PSA should be below detection level after 2 months 2
• Salvage radiotherapy to prostate bed recommended for PSA failure, starting early 2
• First follow-up at 3 months, then yearly visits 2

Following external beam radiotherapy:

• Serum PSA should reach ≤1 ng/mL within 16 months 2

Critical Contraindications and Precautions

Docetaxel should not be administered to:

• Patients with neutrophil counts <1500 cells/mm³ 4
• Patients with bilirubin >ULN or AST/ALT >1.5 × ULN with alkaline phosphatase >2.5 × ULN 4
• Patients with history of severe hypersensitivity reactions to docetaxel or polysorbate 80 4

Common pitfall: A dose of 100 mg/m² docetaxel in previously treated patients is associated with increased hematologic toxicity, infection, and treatment-related mortality 4. The recommended dose is 75 mg/m² every 3 weeks 4.

Patient Selection Considerations

Treatment decisions must account for:

• Patient age, life expectancy, and comorbidities 2
• For patients with life expectancy <10 years and low-risk disease, watchful waiting without curative intent may be more appropriate than active surveillance 1
• Men with comorbid conditions and low-risk disease receive no survival benefit from treatment and are at risk for adverse events without benefit 6
• Patient preferences regarding quality of life trade-offs, particularly erectile dysfunction (increased by 35% with surgery: 80% vs. 45%) and urinary leakage (increased by 28% with surgery: 49% vs. 21%) 2