Prostate Cancer Treatment Guidelines

Risk Stratification and Treatment Selection

• The American College of Radiology and other guideline societies recommend treatment selection for prostate cancer based primarily on risk stratification (very low, low, intermediate, high, and very high/locally advanced) combined with life expectancy, with active surveillance preferred for low-risk disease, radical prostatectomy or radiation therapy for intermediate-risk disease, and radiation therapy plus long-term androgen deprivation therapy for high-risk and locally advanced disease 1
• Risk stratification is essential before selecting treatment, as it determines prognosis and guides therapeutic decisions, according to the National Comprehensive Cancer Network 2
• Very low risk is defined as Gleason score ≤6, PSA <10 ng/mL, <3 positive biopsy cores, ≤50% cancer in any core, PSA density <0.15 ng/mL/g, as per the National Comprehensive Cancer Network guidelines 3
• Low risk is defined as Gleason score ≤6 and PSA <10 ng/mL, according to the American Urological Association and the National Comprehensive Cancer Network 2, 3
• Intermediate risk is defined as Gleason score 7, or PSA 10-20 ng/mL, as per the European Association of Urology and the National Comprehensive Cancer Network guidelines 1, 3
• High risk is defined as Gleason score 8-10, or PSA >20 ng/mL, according to the European Association of Urology and the National Comprehensive Cancer Network 1, 3
• Very high risk/locally advanced is defined as clinical stage T3b-T4, as per the American Joint Committee on Cancer staging manual 1, 3

Staging Workup Requirements

• For intermediate and high-risk disease, cross-sectional imaging (CT or MRI of abdomen and pelvis) and bone scan should be obtained to evaluate for metastases before treatment decisions, as recommended by the National Comprehensive Cancer Network and the European Association of Urology 1, 2
• Low-risk patients do not require staging imaging, according to the American Urological Association and the National Comprehensive Cancer Network 1
• Chest CT should be added for high-risk patients, as per the National Comprehensive Cancer Network guidelines 1

Treatment by Risk Category

• For patients with life expectancy <10 years, observation (watchful waiting) is recommended, involving monitoring without immediate curative intent, with delayed hormone therapy only if symptomatic progression occurs, as per the American Urological Association and the National Comprehensive Cancer Network 2, 3
• For patients with life expectancy ≥10 years, active surveillance is the preferred option, which includes PSA measurement every 6 months, digital rectal examination every 12 months, repeat prostate biopsy every 12 months, and intervention triggered by Gleason score progression or increased tumor volume, according to the National Comprehensive Cancer Network and the European Association of Urology 2, 4
• Alternative curative options for low-risk disease include radical prostatectomy, external beam radiation therapy (minimum 70 Gy), and brachytherapy, as per the American Urological Association and the National Comprehensive Cancer Network 1, 3
• For intermediate-risk disease, radical prostatectomy or radiation therapy plus androgen deprivation therapy (ADT) are the standard treatment options, according to the National Comprehensive Cancer Network and the European Association of Urology 5
• For high-risk localized disease, long-term ADT (2-3 years) plus radical radiation therapy is the preferred treatment based on survival benefit demonstrated in randomized controlled trials, as per the National Comprehensive Cancer Network and the European Association of Urology 1, 4
• For very high risk/locally advanced disease, neoadjuvant ADT plus radical radiation therapy plus adjuvant ADT is the standard approach, according to the National Comprehensive Cancer Network and the European Association of Urology 1, 4

Metastatic Disease

• For metastatic hormone-naïve prostate cancer, ADT combined with novel androgen receptor pathway inhibitors (abiraterone, enzalutamide, apalutamide, or darolutamide) is the standard first-line treatment, as per the National Comprehensive Cancer Network and the European Association of Urology 1, 2
• For castration-resistant metastatic prostate cancer, first-line options include abiraterone, docetaxel, enzalutamide, and radium-223, according to the National Comprehensive Cancer Network and the European Association of Urology 1
• For non-metastatic castration-resistant prostate cancer (M0 CRPC), add second-generation androgen receptor pathway inhibitors to ongoing ADT, as per the National Comprehensive Cancer Network and the European Association of Urology 1

Post-Treatment Surveillance

• After radical prostatectomy, PSA should be undetectable (<0.2 ng/mL) within 2 months, and measure PSA every 6-12 months for first 5 years, then annually, as per the National Comprehensive Cancer Network and the American Urological Association 2, 4
• After external beam radiation therapy, PSA should reach ≤1.0 ng/mL within 16 months, and follow the same PSA monitoring schedule as post-prostatectomy, according to the National Comprehensive Cancer Network and the American Urological Association 3, 4
• For biochemical recurrence (rising PSA), salvage radiation therapy to the prostate bed should be initiated early (PSA <0.5 ng/mL) for improved outcomes, as per the National Comprehensive Cancer Network and the European Association of Urology 2

Shared Decision-Making Considerations

• Patients must be counseled about treatment-related adverse effects, including urinary incontinence, erectile dysfunction, bowel dysfunction, and sexual dysfunction, as per the National Comprehensive Cancer Network and the American Urological Association 1, 6
• Patients should consult with both a urologist and radiation oncologist before making treatment decisions for localized disease, according to the National Comprehensive Cancer Network and the European Association of Urology 1

Indications for Radical Prostatectomy in Localized Prostate Adenocarcinoma

Risk-Based Treatment Algorithm

• The European Association of Urology recommends radical prostatectomy as a standard first-line option for intermediate-risk disease, alongside external beam radiation therapy plus androgen deprivation therapy 7, 8
• For intermediate-risk disease, pelvic lymph node dissection should be performed concurrently based on nomogram estimates of nodal involvement risk, as recommended by the American Urological Association 9, 10
• The Scandinavian Prostate Cancer Group Study 4 demonstrated that radical prostatectomy reduced 12-year prostate cancer mortality from 17.9% to 12.5% compared to watchful waiting, with benefit restricted to men aged ≤65 years, according to the National Comprehensive Cancer Network 7, 8, 11

Pre-Surgical Staging Requirements

• The American College of Radiology recommends bone scan for patients with Gleason score ≥7, PSA ≥10 ng/mL, or bone pain prior to radical prostatectomy 9, 12
• The European Association of Urology recommends omitting bone scan for low-risk patients, as the yield is extremely low 13, 14

Patient Selection Criteria

• The American Urological Association recommends that patients require life expectancy ≥10 years to benefit from curative treatment, and that age and general medical condition do not present absolute contraindications except in exceptional circumstances 7, 9, 11, 12
• The European Association of Urology recommends that patients must be counseled about treatment-related adverse effects, including erectile dysfunction and urinary leakage, which are increased after radical prostatectomy 7, 8, 11

Common Pitfalls to Avoid

• The National Comprehensive Cancer Network recommends against offering radical prostatectomy as first-line treatment for high-risk disease without discussing superior outcomes with radiation plus long-term androgen deprivation therapy 7, 8
• The American Urological Association recommends against performing radical prostatectomy for locally advanced disease, as radiation-based therapy is the standard approach 7, 8
• The European Association of Urology recommends against omitting extended lymphadenectomy in intermediate and high-risk patients undergoing radical prostatectomy 9, 10