What are the treatment guidelines for a patient diagnosed with prostate cancer?

Prostate Cancer Treatment Guidelines

For newly diagnosed prostate cancer, treatment selection depends primarily on risk stratification using Gleason score, PSA level, and clinical stage, with active surveillance recommended for low-risk disease, radical prostatectomy or radiation therapy for intermediate-risk disease, and radiation therapy plus androgen deprivation therapy for high-risk localized disease. 1, 2

Diagnosis and Initial Assessment

Diagnostic Workup

• Do not perform prostate biopsy based on a single elevated PSA—verify with a second measurement 1
• Perform transrectal ultrasound-guided biopsy under antibiotic prophylaxis with local anesthesia, obtaining minimum 10-12 cores 1
• For repeat biopsy after initial negative results, obtain multi-parametric MRI first to guide MRI-TRUS fusion biopsy 1
• Pathology reports must include Gleason score, extent of core involvement, and both the most common and highest Gleason patterns 1

Risk Stratification Framework

Low-risk disease: T1-2a, Gleason ≤6 (Grade Group 1), PSA <10 ng/mL 2, 3

Intermediate-risk disease: Gleason 7 OR PSA 10-20 ng/mL, further subdivided into:

• Favorable: Gleason 3+4, PSA <10, <3 positive cores, <50% core involvement 4, 2
• Unfavorable: Does not meet favorable criteria 4, 2

High-risk disease: T3-4 OR Gleason ≥8 (Grade Group ≥4) OR PSA >20 ng/mL 2, 3

Staging Investigations

Low-Risk Disease

• Bone imaging is not recommended for low-risk disease 1
• Staging investigations generally not required if patient unsuitable for curative treatment due to comorbidities 1

Intermediate and High-Risk Disease

• Perform technetium bone scan AND thoraco-abdominal CT scan OR whole-body MRI OR choline PET/CT for metastatic staging 1
• Obtain pelvic MRI or CT for nodal staging 1
• Consider pelvic MRI when Partin tables indicate >15% risk of nodal involvement 1

Treatment by Risk Category

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

For patients with life expectancy <10 years:

• Watchful waiting with delayed hormone therapy for symptomatic progression 1, 3

For patients with life expectancy >10 years:

• Active surveillance is the preferred option 2, 3
• Active surveillance protocol includes PSA every 6 months, digital rectal examination every 12 months, and repeat biopsy every 12 months 3
• Active surveillance has demonstrated 99% disease-specific survival at 8 years 1
• Radical prostatectomy or radiation therapy are alternatives for patients who prefer definitive treatment 2, 3

Intermediate-Risk Disease (Gleason 7 or PSA 10-20)

Treatment options include:

• Radical prostatectomy with consideration of pelvic lymph node dissection based on nomogram risk estimates 1, 4, 3
• External beam radiation therapy (minimum 70 Gy in 2.0 Gy fractions) with 4-6 months of androgen deprivation therapy 1, 4, 3
• Brachytherapy as monotherapy (for favorable intermediate-risk with Gleason 3+4, PSA <10) or combined with external beam radiation 4, 3

Critical considerations:

• Patients must consult both urologist and radiation oncologist before treatment decision 1
• Radical prostatectomy causes erectile dysfunction in 80% and urinary incontinence in 49% of patients 1
• Brachytherapy should be used cautiously in patients with significant lower urinary tract symptoms 4, 3

High-Risk Localized Disease (T3-4 or Gleason ≥8 or PSA >20)

Standard treatment:

• External beam radiation therapy plus androgen deprivation therapy for minimum 2-3 years 1, 2, 3
• Neoadjuvant LHRH agonist for 4-6 months before radiation, continuing as adjuvant therapy for 2-3 years total 1, 2
• Radical prostatectomy with extended pelvic lymph node dissection may be considered in highly selected cases 1, 2, 3

Locally Advanced Disease (Stage T2b-T4)

For Stage B2-C disease:

• Combination therapy with LHRH agonist (goserelin) plus flutamide, starting 8 weeks before radiation and continuing during radiation 5
• Radiation therapy delivered concurrently 5

Metastatic Disease Management

Hormone-Naive Metastatic Disease

First-line treatment:

• Androgen deprivation therapy (bilateral orchiectomy or LHRH agonist) plus androgen receptor pathway inhibitor (abiraterone, enzalutamide, apalutamide, or darolutamide) 2, 6
• Abiraterone plus ADT improves median overall survival from 36.5 to 53.3 months (HR 0.66) compared to ADT alone 6
• Short-course antiandrogen required to prevent disease flare when starting LHRH agonist 1
• Consider adding docetaxel chemotherapy for extensive disease 2, 6

Castration-Resistant Prostate Cancer (CRPC)

Continue androgen suppression and add:

• First-line options: abiraterone, docetaxel (3-weekly schedule), or enzalutamide 1, 2
• Second-line options after docetaxel: abiraterone, cabazitaxel, enzalutamide, or radium-223 1, 2
• Consider second-line hormonal therapy (antiandrogen, corticosteroid) and third-line therapy (estrogen) 1

Bone Metastases Management

• External beam radiation for painful bone metastases: 1 × 8 Gy or 10 × 3 Gy with equal efficacy 1
• Radioisotope therapy (strontium-89 or samarium-153) for painful bone metastases 1
• Intravenous bisphosphonates (pamidronate) for bone pain resistant to palliative radiation 1
• Manage in collaboration with palliative care services 1

Post-Treatment Management and Surveillance

After Radical Prostatectomy

• PSA should be undetectable (<0.1 ng/mL) within 2 months 3
• Monitor with sensitive PSA assay 1
• For biochemical recurrence (rising PSA): salvage radiation therapy to prostate bed, initiated early when PSA <0.5 ng/mL 1, 2, 3
• Adjuvant radiation immediately after surgery is not routinely recommended but consider for positive surgical margins or extracapsular extension 1, 2

After External Beam Radiation

• PSA should reach ≤1 ng/mL within 16 months 3
• First follow-up at 3 months with PSA measurement, digital rectal examination, and symptom assessment 3

Biochemical Recurrence Management

• Androgen deprivation therapy is not routinely recommended for biochemical recurrence alone 1, 2
• Indications for ADT: symptomatic local disease, proven metastases, or PSA doubling time <3 months 1, 2

Critical Warnings and Contraindications

Androgen Deprivation Therapy Risks

• Monitor for hyperglycemia and diabetes development—check blood glucose and HbA1c periodically 5
• Increased risk of myocardial infarction, sudden cardiac death, and stroke 5
• May prolong QT/QTc interval—avoid in patients with congenital long QT syndrome, correct electrolyte abnormalities, consider ECG monitoring 5
• Tumor flare phenomenon may cause temporary worsening of symptoms, bone pain, ureteral obstruction, or spinal cord compression in first few weeks 5

Treatment Approaches to Avoid

• Do not use primary ADT alone for localized prostate cancer—it does not improve survival 2, 3
• Do not perform PSA screening in men over age 70 years 1
• Population-based PSA screening is not recommended due to overdiagnosis and overtreatment despite mortality reduction 1
• Cryotherapy, HIFU, and focal therapy are not recommended as standard initial treatments 3

Special Precautions

• Brachytherapy can exacerbate urinary obstructive symptoms 4, 3
• Older men experience higher rates of permanent erectile dysfunction and urinary incontinence after prostatectomy 4, 3
• ADT with radiation increases adverse effects on sexual function 4, 3
• Patients receiving bicalutamide monotherapy should receive breast bud irradiation (8-10 Gy single fraction) to prevent painful gynecomastia 1