What are the management options for carcinoma of the prostate?

Management of Carcinoma of the Prostate

Management of prostate cancer must be stratified by risk category, with active surveillance as the preferred approach for low-risk disease, radical treatment (surgery or radiation) for intermediate-risk disease, and radiation therapy combined with long-term androgen deprivation therapy for high-risk localized disease. 1, 2

Initial Diagnosis and Risk Stratification

Risk stratification is the essential first step that determines all subsequent management decisions. 2

• Measure serum PSA and perform digital rectal examination in appropriately counseled patients with clinical suspicion of prostate cancer or those requesting screening 3
• Perform TRUS-guided prostate biopsy under antibiotic prophylaxis with a minimum of 8-10 cores obtained 3, 1
• Report the extent of involvement of each core, the most common and worst Gleason grades 3

Risk categories are defined as follows:

• Very low risk: Gleason ≤6, PSA <10 ng/mL, <3 positive cores, ≤50% cancer in any core, PSA density <0.15 ng/mL/g 2
• Low risk: Gleason ≤6 and PSA <10 ng/mL 2
• Intermediate risk: Gleason 7, or PSA 10-20 ng/mL 2
• High risk: Gleason 8-10, or PSA >20 ng/mL 2
• Very high risk/locally advanced: Clinical stage T3b-T4 2

Staging Workup by Risk Category

Low-risk patients do not require staging imaging. 2

For intermediate-risk disease:

• Consider bone scintigraphy if Gleason score ≥4+3 or PSA ≥15 ng/mL 3
• CT or MRI of pelvis is not well established but may be considered 3

For high-risk disease:

• Perform bone scintigraphy (mandatory) 3
• Perform CT or MRI of pelvis 3, 2
• Add chest CT 2

Management by Risk Category

Low-Risk Disease

Active surveillance is the preferred management option for low-risk prostate cancer, achieving 96% 5-year biochemical recurrence-free rate and only 2.4% prostate cancer-specific mortality at 10 years. 1, 4

Active surveillance protocol includes:

• PSA testing every 3-6 months 1
• Digital rectal examination every 6-12 months 1, 2
• Confirmatory prostate biopsy at 12-24 months after initial diagnosis, with minimum 10-12 cores 1
• Intervention triggered by Gleason score progression or increased tumor volume 2

Alternative curative options for patients declining surveillance:

• Radical prostatectomy 3, 2
• External beam radiotherapy (minimum 70 Gy) using conformal techniques 3, 2
• Brachytherapy with permanent implants or high-dose rate temporary implants 3

Ten-year prostate cancer-specific survival approaches 100% for each management option, including active surveillance. 3

Important caveat: Immediate hormone therapy alone is not recommended for low-risk disease 3

Intermediate-Risk Disease

Definitive treatment is required for patients with ≥10 years life expectancy. 1

Treatment options include:

• Radical prostatectomy 3, 2
• External beam radiotherapy plus short-term androgen deprivation therapy 1, 2
• Brachytherapy with permanent implants (for select favorable intermediate-risk cases) 3, 1

The SPCG-4 trial demonstrated that radical prostatectomy reduced 12-year prostate cancer mortality from 17.9% to 12.5% compared to watchful waiting (NNT=18.5), though this benefit was restricted to men aged ≤65 years. 3

Quality of life considerations: Radical prostatectomy increased erectile dysfunction by 35% (80% vs 45%) and urinary leakage by 28% (49% vs 21%) compared to watchful waiting, though overall quality of life was not significantly worse 3

Important caveat: Immediate hormone therapy alone is not recommended 3

High-Risk and Locally Advanced Disease

External beam radiation therapy combined with long-term androgen deprivation therapy (2-3 years) is the standard approach for high-risk localized disease, with this combination being superior to radiotherapy alone. 1, 2

Treatment options include:

• External beam radiotherapy plus neoadjuvant/adjuvant androgen deprivation therapy (2-3 years) 3, 1, 2
• Radical prostatectomy with pelvic lymph node dissection 3, 4

For locally confined Stage T2b-T4 (Stage B2-C) disease:

• Combine goserelin (ZOLADEX) with flutamide, starting 8 weeks prior to radiation therapy and continuing during radiation 5

Important caveat: Immediate hormone therapy alone is not recommended 3

Lymphadenectomy for staging should be limited to the ilio-obturator regions and performed in patients undergoing surgery with T2a or higher, PSA >15 ng/mL, and Gleason ≥7. 3

Metastatic Hormone-Naïve Disease

Continuous androgen deprivation therapy plus novel androgen receptor pathway inhibitors (abiraterone, enzalutamide, apalutamide, or darolutamide) is the standard first-line treatment for metastatic hormone-naïve prostate cancer. 1, 2

Abiraterone acetate dosing: 1,000 mg orally once daily (taken at least 1 hour before or 2 hours after food) in combination with prednisone 5 mg twice daily 6

Important caveat: Abiraterone must be taken on an empty stomach, as food increases exposure 5-10 fold 6

Castration-Resistant Prostate Cancer

First-line options for castration-resistant metastatic disease include:

• Abiraterone 1, 2
• Enzalutamide 1
• Docetaxel chemotherapy 1, 2
• Radium-223 for bone metastases 1
• Denosumab or zoledronic acid for skeletal-related events 1

Post-Treatment Surveillance

After radical prostatectomy:

• PSA should be undetectable (<0.2 ng/mL) within 2 months 2
• Measure PSA every 3 months during year 1, then every 6 months for 7 years, then annually 1, 2
• Initiate salvage radiotherapy early (PSA <0.5 ng/mL) for biochemical recurrence for maximum effectiveness 1, 2

After radiotherapy:

• PSA should reach ≤1.0 ng/mL within 16 months 2
• Perform PSA determination and digital rectal examination every 6 months indefinitely 1, 2
• Early androgen deprivation therapy is not routinely recommended unless symptomatic local disease, proven metastases, or PSA doubling time <3 months 1

Treatments to Avoid

The following approaches should not be used:

• Cryotherapy, HIFU, and focal therapy as standard initial treatment (regarded as options in current development only) 3
• Cryosurgery as primary therapy due to lack of long-term comparative data 1
• Pure anti-androgens (associated with poorer outcomes compared to watchful waiting) 1
• Combined androgen blockade routinely 1
• Chemotherapy for nonmetastatic disease 1

Quality Benchmarks

Expected complication rates:

• Incontinence requiring >2 pads daily at 1 year should occur in <5% after prostatectomy 1
• Severe late radiation complications to bladder/rectum should be <5% at 2 years 1
• All patients undergoing radical treatment should be followed in specialized units with systematic data collection 1

Special Considerations for Watchful Waiting

Watchful waiting with delayed hormone therapy is appropriate for:

• Men with life expectancy <10 years 3, 2
• Men unsuitable for or unwilling to have radical treatment 3
• This involves monitoring without immediate curative intent, with delayed hormone therapy only if symptomatic progression occurs 2