What is the recommended diagnostic workup and risk‑adapted treatment strategy for a man over 50 years old with suspected prostate cancer and no other comorbidities?

Prostate Cancer: Diagnosis and Treatment

Diagnostic Workup

For a man over 50 with suspected prostate cancer, measure serum PSA and perform digital rectal examination (DRE), then proceed to transrectal ultrasound-guided biopsy with 10–12 cores if either test is abnormal. 1

Initial Evaluation

• Measure serum PSA in appropriately counseled patients with clinical suspicion or those requesting screening 1
• Verify a single elevated PSA with a second measurement before proceeding to biopsy—40–44% of initially elevated values normalize without intervention 1, 2
• Perform DRE to assess clinical T stage, as high-grade cancer can occur even with "normal" PSA levels 1

Biopsy Indications and Technique

The decision to biopsy should incorporate PSA level, DRE findings, ethnicity, age, comorbidities, free/total PSA ratio, and prior biopsy history 1. Proceed to biopsy when:

• PSA ≥4.0 ng/mL (confirmed on repeat testing) 1
• Abnormal DRE regardless of PSA level 1
• PSA 2.5–4.0 ng/mL with additional risk factors (African American ethnicity, family history, suspicious DRE) 3

Biopsy protocol:

• Perform under antibiotic prophylaxis and local anesthesia 1
• Obtain minimum 10–12 cores via transrectal ultrasound guidance 1
• For repeat biopsy after initial negative result, obtain multiparametric MRI first with MRI-guided or MRI-TRUS fusion biopsy 1

Pathology Reporting

The pathology report must document the extent of involvement in each core, the most dominant Gleason pattern, and the pattern with highest Gleason grade 1

Staging and Risk Assessment

Risk Stratification

Categorize localized prostate cancer as low, intermediate, or high risk 1:

• Low risk: T1–2a AND Gleason <7 AND PSA <10 ng/mL
• High risk: T3–4 OR Gleason ≥8 OR PSA >20 ng/mL
• Intermediate risk: All remaining cases

Staging Investigations

Low-risk disease:

• No imaging routinely required 1
• Bone scan generally unnecessary when PSA <20 ng/mL and no Gleason pattern 4 or 5 1
• Pelvic imaging (CT/MRI) generally unnecessary when PSA <10 ng/mL and Gleason <7 1

Intermediate-risk disease:

• Consider bone scintigraphy if Gleason ≥4+3 or PSA ≥15 ng/mL 1
• Pelvic imaging role not well established 1

High-risk disease:

• Perform technetium bone scan 1
• Obtain pelvic CT or MRI for nodal staging 1
• Consider whole-body MRI or choline PET/CT 1

Treatment Strategy

Low-Risk Localized Disease (T1–2a, Gleason <7, PSA <10)

Active surveillance with selected delayed intervention is appropriate for many patients and achieves 99% disease-specific survival at 8 years. 1 Treatment options include:

• Active surveillance with serial PSA, prostate biopsies, or MRI—initiate treatment if Gleason score or tumor stage increases 4
• Radical prostatectomy 1
• External beam radiotherapy (minimum 74 Gy in 2.0 Gy fractions or equivalent using conformal, image-guided techniques) 1
• Brachytherapy with permanent implants 1

The only randomized trial comparing radical prostatectomy to watchful waiting showed 5% absolute improvement in 10-year overall survival (73% vs 68%, P=0.04), though these results may not generalize to screen-detected cancers 1. Radical prostatectomy increased erectile dysfunction by 35% (80% vs 45%) and urinary leakage by 28% (49% vs 21%) compared to watchful waiting 1.

Intermediate and High-Risk Disease

There is no consensus on optimal management—patients must be informed of potential benefits and harms of different options. 1 Men should consult both an urologist and radiation oncologist 1.

Treatment options include:

• Radical prostatectomy 1
• External beam radiotherapy with or without hormone therapy 1, 5
• Watchful waiting with delayed hormone therapy for symptomatic progression (appropriate for men unsuitable for or unwilling to have curative treatment) 1

Metastatic Disease

First-line therapy combines androgen deprivation with androgen receptor pathway inhibitors. 4

• Medical castration with gonadotropin-releasing hormone agonists forms the foundation 4
• Add androgen receptor pathway inhibitors (abiraterone, darolutamide)—abiraterone improved median overall survival from 36.5 to 53.3 months (HR 0.66,95% CI 0.56–0.78) compared to castration alone 4
• Consider chemotherapy (docetaxel) for extensive disease—demonstrated 2–2.5 month survival improvement in hormone-refractory disease 4, 5

Critical Counseling Points

All patients must understand that prostate cancer treatment may cause:

• Sexual dysfunction and infertility 1
• Urinary incontinence 1
• Bowel problems 1

Population screening is not recommended because 781 men need invitation for screening and 27 need treatment to prevent one prostate cancer death, with no reduction in overall mortality 1. Individual risk-adapted testing with shared decision-making is the appropriate approach 1.