What are the treatment options for prostate cancer?

Treatment Options for Prostate Cancer

Treatment selection for prostate cancer must be stratified by risk category, with active surveillance as the primary strategy for low-risk disease, radical prostatectomy or radiation therapy for intermediate-risk disease, and radiation therapy combined with 2-3 years of androgen deprivation therapy for high-risk localized disease. 1

Risk Stratification Framework

Treatment decisions depend on three critical factors that determine prognosis 1:

• Very Low Risk: T1c, Gleason ≤6, PSA <10 ng/mL, <3 positive biopsy cores, ≤50% cancer in any core, PSA density <0.15 ng/mL/g 1
• Low Risk: T1-T2a, Gleason ≤6, PSA <10 ng/mL 1
• Intermediate Risk: T2b-T2c, Gleason 7, or PSA 10-20 ng/mL 1
• High Risk: T3a, Gleason 8-10, or PSA >20 ng/mL 1
• Very High Risk: T3b-T4 (locally advanced) 1

Treatment by Risk Category and Life Expectancy

Very Low and Low Risk Disease

For patients with life expectancy <10 years: Observation (watchful waiting) without routine biopsies is recommended 1. This approach avoids treatment-related morbidity in men unlikely to die from prostate cancer.

For patients with life expectancy 10-20 years: Active surveillance is the preferred management strategy 1, 2. The protocol includes 1:

• PSA testing every 3-6 months
• Digital rectal examination every 6-12 months
• Repeat prostate biopsy within 6-12 months of diagnosis, then at least every 12 months
• Intervention triggered by PSA progression, grade reclassification to Gleason 4 or 5, or increased tumor volume 2

The evidence supporting this approach is compelling: prostate cancer-specific mortality is only 2.4% at 10 years for low-risk patients on active surveillance, while treatment enhances quality-adjusted survival by merely 1.2 months but causes significant urinary, sexual, and bowel dysfunction 1, 2.

For patients with life expectancy >20 years: Active surveillance, radiation therapy (external beam or brachytherapy), or radical prostatectomy are all viable options 1. However, active surveillance remains appropriate given the excellent long-term outcomes, with metastatic progression rates <1% at 15 years for very low-risk patients 1.

Critical pitfall: Approximately 55% of low-risk patients receive unnecessary treatment due to provider bias and patient misunderstanding of the minimal survival benefit 1, 2. Patients must be counseled that active surveillance maintains curability while avoiding treatment side effects 2.

Intermediate Risk Disease

For patients with life expectancy <10 years: Options include observation, radiation therapy with or without 4-6 months of androgen deprivation therapy (ADT), with or without brachytherapy, or brachytherapy alone 1.

For patients with life expectancy ≥10 years: The primary options are 1:

• Radical prostatectomy with pelvic lymph node dissection if predicted probability of lymph node metastasis ≥2%
• External beam radiation therapy with or without 4-6 months of ADT, with or without brachytherapy
• Brachytherapy alone for favorable intermediate-risk patients (T1c, Gleason 7, low volume)

Active surveillance is NOT recommended for intermediate-risk patients with life expectancy >10 years 1. The Scandinavian Prostate Cancer Group Study demonstrated that radical prostatectomy improves overall survival and prostate cancer-specific survival compared to watchful waiting at 10 years 1.

High Risk Disease

The preferred treatment is external beam radiation therapy combined with 2-3 years of ADT (Category 1 recommendation) 1. This combination has been shown in randomized controlled trials to prolong survival compared to radiation alone 1. ADT alone is insufficient for high-risk disease 1.

Alternative options include 1:

• External beam radiation plus brachytherapy with or without 2-3 years of ADT
• Radical prostatectomy with pelvic lymph node dissection in selected patients (subset may benefit from surgery)

Important caveat: Patients with low-volume, high-grade tumors warrant aggressive local radiation combined with typically 2-3 years of ADT 1. The optimal duration of ADT in combination with brachytherapy remains unclear 1.

Very High Risk (Locally Advanced) Disease

Treatment options in order of preference 1:

1. Radiation therapy plus long-term ADT (Category 1 recommendation)
2. External beam radiation plus brachytherapy with or without long-term ADT
3. Radical prostatectomy plus pelvic lymph node dissection in selected patients without fixation to adjacent organs
4. ADT alone for patients not eligible for definitive therapy

Metastatic Castration-Resistant Prostate Cancer

For metastatic hormone-naive disease, first-line treatment options include 1:

• ADT plus abiraterone (improved median overall survival from 36.5 to 53.3 months, HR 0.66) 3
• ADT plus docetaxel (especially for extensive disease) 3
• ADT plus enzalutamide 1
• ADT plus apalutamide 1

For castration-resistant disease, first-line options include abiraterone, docetaxel, or enzalutamide 1. Docetaxel 75 mg/m² every 3 weeks with prednisone 5 mg twice daily is FDA-approved for metastatic castration-resistant prostate cancer 4.

Shared Decision-Making Requirements

Counseling must explicitly address 1:

• Cancer severity (risk category)
• Patient values and preferences
• Life expectancy and comorbidities
• Pre-treatment functional status (urinary, sexual, bowel function)
• Expected post-treatment functional outcomes
• Potential for salvage treatment

Patients should meet with both urology and radiation oncology specialists when possible to promote informed decision-making 1. This is critical because 93% of urologists recommend surgery while 72% of radiation oncologists recommend radiotherapy for the same hypothetical patient 1.

Treatments NOT Recommended

• Cryotherapy or other local therapies as routine primary therapy for localized prostate cancer due to lack of long-term comparative data 1
• ADT as primary treatment for localized prostate cancer (does not improve survival) 1
• Active surveillance for intermediate-risk patients with life expectancy >10 years 1

Radiation Therapy Technical Specifications

When radiation is selected 1, 5:

• External beam radiation should be delivered using conformal techniques to minimum target dose of 70 Gy in 2.0 Gy fractions or equivalent
• Conformal radiotherapy reduces late toxicity compared to conventional radiotherapy
• Iridium is the standard isotope for temporary implant brachytherapy 5