What are the treatment options for prostate cancer?

Prostate Cancer Management

Treatment selection for prostate cancer depends primarily on risk stratification (low, intermediate, high, or metastatic disease) combined with life expectancy, with active surveillance strongly preferred for low-risk disease, radical prostatectomy or radiation therapy for intermediate-risk disease, and radiation therapy plus long-term androgen deprivation therapy (ADT) for high-risk disease. 1, 2

Risk Stratification Framework

Risk stratification must be completed before selecting any treatment approach, as it determines both prognosis and therapeutic decisions 2:

• Low-risk disease: PSA <10 ng/mL AND Gleason score ≤6 AND clinical stage T1-T2a 1, 2
• Intermediate-risk disease: PSA 10-20 ng/mL OR Gleason score 7 OR clinical stage T2b 1, 2
• High-risk disease: PSA >20 ng/mL OR Gleason score 8-10 OR clinical stage T2c 1, 2
• Very high-risk/locally advanced: Clinical stage T3b-T4 2

Life expectancy is critical—curative treatment is generally not recommended for patients with life expectancy <10 years, as observation (watchful waiting) is the appropriate strategy. 1, 2

Staging Workup Requirements

Before treatment decisions:

• Low-risk patients do not require staging imaging 2
• Intermediate and high-risk disease requires cross-sectional imaging (CT or MRI of abdomen/pelvis) and bone scan to evaluate for metastases 2
• High-risk patients should also receive chest CT 2

Treatment by Risk Category

Low-Risk Disease (Life Expectancy ≥10 Years)

Active surveillance is the preferred option for low-risk prostate cancer. 1, 2 This approach involves:

• PSA measurement every 6 months 2
• Digital rectal examination every 12 months 2
• Repeat prostate biopsy every 12 months 2
• Intervention triggered by Gleason score progression or increased tumor volume 2

Active surveillance is safe, with prostate cancer-specific mortality only 2.4% at 10 years in low-risk patients. 3 Treatment enhances quality-adjusted survival by only 1.2 months in low-risk patients, while causing urinary, sexual, and bowel dysfunction 3.

Alternative curative options if active surveillance is declined include radical prostatectomy, external beam radiation therapy (minimum 70 Gy), or brachytherapy 2.

Intermediate-Risk Disease

Radical prostatectomy or radiation therapy plus short-term ADT (4-6 months) are the standard treatment options. 3, 1, 2 These treatments are almost equivalent in effectiveness but have different adverse effect profiles 3:

• Radical prostatectomy: Higher rates of urinary incontinence and erectile dysfunction, especially in older men 3
• Radiation therapy: Higher rates of bowel dysfunction and proctitis 3
• Brachytherapy: Can be offered alone or combined with external beam radiation therapy for favorable intermediate-risk disease 3, 1

Pelvic lymph node dissection (PLND) is recommended for unfavorable intermediate-risk disease at prostatectomy. 3

High-Risk Localized Disease

Long-term ADT (24-36 months) plus external beam radiation therapy is the preferred treatment based on survival benefit demonstrated in randomized controlled trials. 3, 1, 2 This combination is superior to radiation therapy alone 3.

Radical prostatectomy is an alternative for high-risk disease, with consideration of adjuvant radiotherapy when locally extensive cancer is found. 3, 1

Very High-Risk/Locally Advanced Disease

Neoadjuvant ADT plus radical radiation therapy plus adjuvant ADT is the standard approach. 2

Metastatic Disease Management

Metastatic Hormone-Naïve Prostate Cancer

Continuous ADT plus novel androgen receptor pathway inhibitors (abiraterone, enzalutamide, apalutamide, or darolutamide) is the standard first-line treatment. 2, 4 Use of abiraterone improved median overall survival from 36.5 months to 53.3 months compared with medical castration alone 5.

For patients fit enough to receive chemotherapy, ADT plus docetaxel is first-line treatment, especially for extensive disease. 1, 6 Docetaxel is administered at 75 mg/m² every 3 weeks with prednisone 5 mg orally twice daily 6.

Castration-Resistant Prostate Cancer

For metastatic castration-resistant prostate cancer, first-line options include abiraterone, docetaxel, enzalutamide, and radium-223. 1, 2

For non-metastatic castration-resistant prostate cancer (M0 CRPC), add second-generation androgen receptor pathway inhibitors to ongoing ADT. 2

Post-Treatment Surveillance and Salvage Therapy

After Radical Prostatectomy

• PSA should be undetectable (<0.2 ng/mL) within 2 months 2
• Measure PSA every 6-12 months for first 5 years, then annually 2
• For biochemical recurrence (rising PSA), salvage radiotherapy to the prostate bed should be initiated early (PSA <0.5 ng/mL) for improved outcomes 1, 2

After Radiation Therapy

• PSA should reach ≤1.0 ng/mL within 16 months 2
• Follow same PSA monitoring schedule as post-prostatectomy 2
• Early ADT is not routinely recommended for biochemical recurrence unless patients have symptomatic local disease, proven metastases, or PSA doubling time <3 months 1

Critical Adverse Effects and Counseling

Patients must be counseled about treatment-related adverse effects before making decisions 2:

• Radical prostatectomy: Urinary incontinence and erectile dysfunction, with higher rates in older men 3
• Radiation therapy: Erectile dysfunction, proctitis, and bowel dysfunction 3
• Brachytherapy: Similar effects as external beam radiation therapy regarding erectile dysfunction and proctitis, but can exacerbate urinary obstructive symptoms 3
• ADT with radiation: Increases likelihood and severity of sexual dysfunction and causes systemic side effects 3

Patients should consult with both a urologist and radiation oncologist before making treatment decisions for localized disease. 2

Common Pitfalls to Avoid

• Overtreatment of low-risk disease: Proper counseling about active surveillance as a safe option is essential, as approximately 55% of low-risk patients receive unnecessary treatment 3, 1
• Delayed salvage radiotherapy: Most effective when PSA is <0.5 ng/mL after prostatectomy 1, 2
• Ignoring life expectancy: Curative treatment offers minimal benefit when life expectancy is <10 years 1, 2
• Inadequate biopsy sampling: A minimum of 10-12 cores should be obtained to avoid missing cancer 1