Prostate Cancer
An androgen-dependent adenocarcinoma of the prostate gland, often asymptomatic early on but can progress to metastatic bone disease if untreated.
- Sudden onset lower extremity weakness (Spinal Cord Compression).
Emergency Management: Malignant Spinal Cord Compression (MSCC): Requires immediate Dexamethasone 10-16 mg IV and urgent MRI.
Prostate cancer is a malignant neoplasm arising from the epithelial cells of the prostate gland, most commonly in the peripheral zone. It is typically an adenocarcinoma and relies heavily on androgenic stimulation for growth and survival. The disease spectrum ranges from slow-growing indolent tumors to highly aggressive metastatic disease, commonly spreading to bones and lymph nodes.
Detailed Overview
Prostate cancer is the most common non-cutaneous cancer in men globally. It is driven by androgen receptor (AR) signaling, which promotes cellular proliferation and inhibits apoptosis. Early stages are often asymptomatic, making screening with Prostate-Specific Antigen (PSA) and digital rectal exam (DRE) critical for early detection. The clinical course is highly variable; many low-risk tumors never progress to cause morbidity, while high-risk variants can rapidly metastasize, primarily causing osteoblastic bone lesions and associated skeletal complications.
Epidemiology & Demographics
Incidence is roughly 110 per 100,000 men globally, peaking in the 7th and 8th decades of life. Median age at diagnosis is 66 years. Lifetime risk is approximately 1 in 8 for men in the US. Incidence is significantly higher in African American men.
Etiological Mechanism
The primary etiology involves genetic mutations in prostatic epithelial cells, often linked to advanced age, familial inheritance (e.g., BRCA1/BRCA2, HOXB13 mutations), and environmental factors. Androgen receptor activation is a crucial driving factor.
Primary Causes
Genetic Mutations (BRCA2, HOXB13)
Age-related accumulation of cellular damage
Hormonal influences (Androgens)
- Advanced Age: Risk increases exponentially after age 50; over 60% of cases are diagnosed in men older than 65.
- Race/Ethnicity: African American men have the highest incidence and mortality rates globally.
- Family History: First-degree relative with prostate cancer doubles the risk.
Prostate cancer typically originates in the peripheral zone of the gland as prostatic intraepithelial neoplasia (PIN), which progresses to invasive adenocarcinoma. Tumor growth is initially dependent on androgens binding to the androgen receptor (AR), leading to the transcription of target genes that stimulate proliferation and inhibit apoptosis. As the disease progresses, genetic alterations such as PTEN loss and TMPRSS2-ERG gene fusions occur. Metastasis primarily happens hematogenously to the axial skeleton, leading to characteristic osteoblastic bone metastases.
Characteristic Clinical Presentation
- Urinary Hesitancy and Weak Stream: Difficulty initiating urination and a weak urinary flow due to urethral compression.
- Hematuria: Blood in the urine caused by tumor invasion into the urethra.
- Bone Pain: Deep, aching pain in the back, hips, or pelvis, indicative of osteoblastic bone metastases.
Physical Examination Signs
- Abnormal Digital Rectal Exam (DRE)
- Lower Extremity Edema
- Spinal Cord Compression: Oncologic emergency caused by vertebral bone metastases pressing on the spinal cord.
- Pathological Fractures: Fractures occurring in bones weakened by metastatic lesions.
Diagnostic Criteria & Guidelines
Diagnosis is confirmed via a transrectal ultrasound (TRUS)-guided core needle biopsy showing adenocarcinoma. Histologic grading uses the Gleason Scoring System.
Differential Diagnosis
- Benign Prostatic Hyperplasia (BPH)
- Prostatitis
Laboratory Tests & Biomarkers
- Prostate-Specific Antigen (PSA): Elevated > 4.0 ng/mL, though rapid velocity (>0.35 ng/mL/yr) is concerning.
- Alkaline Phosphatase (ALP): Elevated in the presence of osteoblastic bone metastases.
Imaging Modalities & Findings
- Multiparametric MRI:
- Bone Scan:
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Stage I
Tumor involves <= one-half of one lobe, non-palpable (T1a-T1c), Gleason score <= 6, PSA < 10 ng/mL.
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Stage IV
Tumor is fixed or invades adjacent structures (T4), or involves lymph nodes (N1) or distant metastases (M1, often bone).
For localized, low-risk disease: Active Surveillance. For localized, high-risk disease: Radical Prostatectomy OR External Beam Radiation Therapy (EBRT) + Androgen Deprivation Therapy (Leuprolide 22.5 mg IM every 3 months).
Second-Line & Adjunctive Therapy
For metastatic castration-resistant prostate cancer: Enzalutamide 160 mg PO daily or Abiraterone acetate 1000 mg PO daily with Prednisone 5 mg PO BID.
Surgical & Procedural Management
Radical Prostatectomy involving removal of the entire prostate gland and seminal vesicles.
Recommended Lifestyle Changes
- Maintain BMI < 25 kg/m2.
- Exercise for at least 150 minutes per week.
- Diet rich in lycopene.
Patient Counseling & Advice
Discuss the trade-offs between definitive local therapies, specifically risks of stress urinary incontinence and erectile dysfunction.
Follow-Up & Monitoring Schedule
PSA every 3-6 months for 5 years. A PSA > 0.2 ng/mL following radical prostatectomy indicates biochemical recurrence.
Preventive Strategies
No definitive pharmacological prevention. 5-ARIs are not broadly recommended for prevention.
Excellent for localized disease with a 5-year survival rate >99%. Distant metastatic disease has a 5-year survival rate of ~32%.
Frequently Asked Questions
View Official Guideline