What is the recommended treatment for prostate cancer?

Treatment of Prostate Cancer

The recommended treatment for prostate cancer depends critically on disease stage and risk stratification, with localized low-risk disease managed by active surveillance, radical prostatectomy, or radiotherapy; intermediate/high-risk localized disease treated with surgery or radiotherapy plus androgen deprivation therapy (ADT); and metastatic disease requiring continuous ADT with or without docetaxel chemotherapy. 1

Risk Stratification and Staging

Before selecting treatment, classify localized disease as low-, intermediate-, or high-risk based on PSA level, Gleason score, and clinical T stage 1:

• Low-risk: T1-2a, Gleason ≤6, PSA <10 ng/mL
• Intermediate-risk: T2b-2c, Gleason 7, or PSA 10-20 ng/mL
• High-risk: T3a or Gleason 8-10 or PSA >20 ng/mL

For intermediate- or high-risk disease, perform nodal staging with CT, MRI, choline PET/CT, or pelvic nodal dissection, and stage for metastases using technetium bone scan and thoraco-abdominal CT 1.

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

Active surveillance is the preferred option for low-risk disease, as no benefit for active treatment has been demonstrated in overall survival. 1

Alternative curative options include 1:

• Radical prostatectomy
• External beam radiotherapy (minimum 70 Gy in 2.0 Gy fractions or equivalent) 1
• Brachytherapy with permanent implants

Watchful waiting with delayed hormone therapy is appropriate for men not suitable for or unwilling to have radical treatment 1.

Intermediate-Risk Disease

Treatment options include 1:

• Radical prostatectomy with consideration of lymph node dissection based on nomogram estimates
• External beam radiotherapy plus ADT for 4-6 months (neoadjuvant and concurrent) 1
• High-dose rate brachytherapy

Primary ADT alone is not recommended as standard initial treatment of non-metastatic disease. 1

High-Risk or Locally Advanced Disease (T3-4)

External beam radiotherapy plus hormone treatment for at least 2 years is the recommended approach. 1

Specifically 1:

• Neoadjuvant LHRH agonist therapy for 4-6 months is recommended
• Adjuvant hormonal therapy for 2-3 years is recommended for men at high risk of prostate cancer mortality
• Radical prostatectomy plus extended pelvic lymphadenectomy can be considered in highly selected cases 1

Post-Operative Management

Immediate post-operative radiotherapy after radical prostatectomy is not routinely recommended. 1

However, patients with positive surgical margins or extracapsular extension should be informed about pros and cons of adjuvant radiotherapy 1.

For PSA failure after radical prostatectomy, salvage radiotherapy to the prostate bed should start early (e.g., PSA <0.5 ng/mL) 1.

Biochemical Relapse After Radical Therapy

Early ADT is not routinely recommended for men with biochemical relapse unless they have symptomatic local disease, proven metastases, or PSA doubling time <3 months. 1

For men with biochemical relapse after radical radiotherapy who start ADT, intermittent ADT is recommended over continuous therapy due to quality-of-life benefits 1.

Metastatic Hormone-Naïve Disease

Continuous ADT (bilateral orchiectomy or LHRH agonists) is the recommended first-line treatment. 1

For patients fit enough for chemotherapy, ADT plus docetaxel is recommended as first-line treatment, as this combination improves survival. 1, 2

Key implementation details 1, 2:

• When starting LHRH agonist, give antiandrogen for 3-4 weeks to prevent testosterone flare
• Combined androgen blockade (CAB) with castration plus antiandrogen shows minimal survival benefit (1-5% absolute reduction at 5 years) with high cost 1
• First-line hormonal management should be based on castration only, not routine CAB 1
• Inform men starting ADT that regular exercise reduces fatigue and improves quality of life 1

Castration-Resistant Prostate Cancer (CRPC)

Patients who develop CRPC should continue androgen suppression. 1

Chemotherapy-Naïve Metastatic CRPC

For asymptomatic/mildly symptomatic patients 1, 2:

• Abiraterone or enzalutamide are recommended first-line options
• Radium-223 is recommended for bone-predominant, symptomatic disease without visceral metastases

Symptomatic Metastatic CRPC

Docetaxel using a 3-weekly schedule is recommended for symptomatic, castration-resistant disease. 1, 2

Post-Docetaxel CRPC

In patients progressing after docetaxel, recommended options include 1:

• Abiraterone (if not used previously)
• Enzalutamide (if not used previously) 3
• Cabazitaxel
• Radium-223 (in those without visceral disease)

Bone Metastases Management

A single fraction of external beam radiotherapy is recommended for palliation of painful bone metastases. 1, 2

In patients with bone metastases from CRPC at high risk for skeletal-related events, denosumab or zoledronic acid can be recommended 1, 2.

MRI of the spine to detect subclinical cord compression is recommended in men with CRPC with vertebral metastases. 1, 2

Monitoring During Treatment

Men on long-term ADT should be monitored for side effects including 1, 2:

• Osteoporosis (using bone densitometry)
• Metabolic syndrome
• Cardiovascular risk factors 3

Following radical prostatectomy, serum PSA should be below detection level after 2 months 1.

Important Caveats

• Patients with neuroendocrine differentiation should receive chemotherapy in addition to ADT, as PSA is not a reliable indicator in this population 1, 2
• To prevent painful gynecomastia with antiandrogen therapy, breast bud irradiation (8-10 Gy in one fraction) should be given 1
• Enzalutamide carries risk of seizure (0.6% overall, 2.2% in predisposing factors); permanently discontinue if seizure occurs 3