Prostate Cancer Pathophysiology

Prostate Cancer Pathophysiology

• Risk of developing prostate cancer: 1 in 6 men
• Second leading cause of cancer death in men aged over 65
• 85% of men diagnosed with prostate cancer are over 65
• Exact cause often unknown
• Risk factors:
  • Advancing age
  • Family history of prostate cancer
  • Black race
  • Smoking
  • High intake of fats and meat
  • Low intake of lycopene (tomato-based products and fruit)
  • High dietary calcium

Prostate Cancer Pathophysiology: Malignant Transformation

• Malignant transformation of prostate epithelial cells is a series of initiating and promoting events
• Genetic and environmental influences contribute
• 5-10% of cases linked to inherited genetic factors
• HPC1 is a hereditary prostate cancer gene
• More than 95% of primary prostate cancers are adenocarcinomas
• Androgens and estrogens support carcinogenesis, promoting prostate epithelial cell proliferation

Prostate Cancer Pathophysiology: Premalignant Changes

• Premalignant changes in prostate cancer patients include prostatic intraepithelial neoplasia (PIN)
• PIN lesions can progress to prostate adenocarcinoma

Prostate Cancer Pathophysiology: Tumor Location

• Neoplasm develops in the peripheral portion of the gland
• Due to location, tumor compression of the urethra is a late clinical event

Prostate Cancer Clinical Manifestations

• Often asymptomatic until advanced stages
• Clinical manifestations appear when tumor has expanded
• Obstructing urethra is a symptom
• Can present with similar symptoms to benign prostatic hyperplasia (BPH)
• Common systemic manifestations include paraneoplastic syndromes
• Manifestations of metastatic spread, including bone pain

Prostate Cancer Diagnostic Criteria

• Diagnostic tools include:
  • Digital rectal examination
  • Transrectal ultrasound
  • Prostate-specific antigen (PSA) test
  • Biopsy via fine-needle aspiration transrectally
  • Pelvic lymph node dissection during radical prostatectomy
  • Radionucleotide bone scans to detect metastases
  • Most common site of distant metastasis

Prostate Cancer Diagnostic Criteria: Staging

• Staging uses the TNM classification system:
  • T1: Clinically inapparent tumor (not palpable or visible)
  • T2: Tumor confined to the prostate
  • T3: Tumor extends through the prostate capsule
  • T4: Tumor invades adjacent structures except seminal vesicles
• Survival rates and prognosis are linked to:
  • Histologic features
  • Staging
  • Local/regional spread (5-year survival >99%)
  • Distant metastases (5-year survival 33.5%)

Prostate Cancer Treatment

• Treatment is based on tumor grading, TNM classification, age, and overall health.
• Treatment options include:
  • Surgery: radical prostatectomy
  • Radiation therapy (adjuvant)
  • Chemotherapy (adjuvant)
  • Androgen-deprivation hormone therapy to decrease cell proliferation
  • "Watchful waiting" for slow-growing tumors diagnosed later in life
• This approach can avoid complications of more aggressive treatments (surgery, radiation, chemo).
• Many older men die of causes other than prostate cancer.