Carcinoma of the prostate

1. Overview

• Most common visceral cancer in males.
• #2 cancer-related death in men (after lung).
• Disease of older men (> 50 yr).
• 95 % = acinar-type adenocarcinoma.

2. Pathogenesis

A) Hormonal

• Androgens provide the “soil” for tumor development — prostate is androgen-dependent.

B) Hereditary

• ↑ Risk with first-degree relatives affected (familial).
• More common in African-Americans than whites or Asians.

C) Genetic

• TMPRSS2-ETS fusion gene — androgen-regulated promoter fused with ETS transcription factor coding sequence.
• PI3K / AKT pathway activation by loss-of-function PTEN mutation → tumor cell growth + survival.

D) Environmental

• Industrial settings, geographic differences.
• Diet rich in animal fat, smoking.

3. Morphology

• Most cancers not visible grossly at detection.
• Advanced: firm, gray-white to yellow lesions infiltrating adjacent glands.
• Arises in peripheral zone (posterior) — palpable on DRE.
• Histology:
  • Adenocarcinoma; well-differentiated to anaplastic.
  • Glands lined by single cuboidal cell layer WITHOUT basal cells (loss of basal cells = key diagnostic feature).
• Precursor lesion: High-grade prostatic intraepithelial neoplasia (HGPIN).

4. Clinical Features

• Often clinically silent in early stages; discovered accidentally.
• DRE: hard, irregular nodules, fixed prostate.
• Extensive cancers → local discomfort + urethral complications (late since peripheral zone).
• Aggressive carcinomas may present with metastases:
  • Bone metastases — commonly osteoblastic (bone-forming) lesions; can be osteolytic.
  • Lumbar spine + pelvis + femur are favored sites.
  • Local invasion: seminal vesicles, bladder, rectum.
  • Lymphatic + hematogenous spread.

5. Treatment

• Surgery (radical prostatectomy).
• Radiation.
• Hormonal manipulation (androgen deprivation): GnRH agonists (leuprolide), antiandrogens (flutamide); for advanced.

6. Diagnosis

Digital Rectal Exam (DRE)

• Recommended every 2 yr for men 55–69 yr.
• Palpable hard nodule in peripheral zone.

Prostate-Specific Antigen (PSA)

• Proteolytic enzyme secreted into semen.
• Prostate cancer secretes 10× the PSA of normal tissue (normal level < 4 ng/mL).
• Prostate-specific but NOT cancer-specific: also ↑ in BPH, prostatitis, ejaculation, instrumentation.
• Best used with other screening methods + to monitor therapy response.
• PSA > 10 ng/mL → high suspicion; biopsy.

Biopsy

• Definitive diagnosis via transrectal ultrasound-guided biopsy.

7. Gleason Grading

• Refers to how abnormal cells look + likelihood of progression.
• Low Gleason score → well-differentiated, not aggressive.
• High Gleason score → least differentiated, aggressive.

Pattern	Description	Differentiation
1	Small, uniform glands	Well-differentiated
2	More stroma between glands	Well-differentiated
3	Distinctly infiltrative margins	Moderately differentiated
4	Irregular masses of neoplastic glands	Poorly differentiated / anaplastic
5	Only occasional gland formation	Poorly differentiated / anaplastic

• Final score: sum of two most prevalent patterns (range 2–10).
• Score ≤ 6 = low risk; 7 = intermediate; ≥ 8 = high risk.

8. Comparison — BPH vs Prostate Carcinoma

Feature	BPH	Prostate carcinoma
Zone	Transitional (periurethral)	Peripheral (posterior)
DRE	Smooth, rubbery, enlarged	Hard nodule, irregular, fixed
PSA	Mildly ↑	Markedly ↑ (> 10 ng/mL)
Basal cells	Preserved	Lost
Sx onset	Early obstruction	Late (silent until advanced)
Bone mets	None	Osteoblastic

💡 High-yield: #1 visceral cancer in men, #2 cancer death. Acinar adenocarcinoma 95 %, peripheral zone (palpable on DRE = hard nodule). Pathogenesis: TMPRSS2-ETS fusion, PTEN loss, androgen-dependent. African-Americans ↑ risk. Histology: glands without basal cells. Bone mets = osteoblastic (lumbar spine, pelvis, femur). Diagnosis: DRE + PSA (10× ↑; not cancer-specific) + biopsy. Gleason grading (sum of 2 most prevalent patterns, 2–10). Tx: surgery + radiation + androgen deprivation (GnRH agonists, antiandrogens) for advanced. Precursor = HGPIN.