Prostate Adenocarcinoma
~Introduction
Prostate adenocarcinoma is the most common malignant tumor of the prostate gland and one of the leading causes of cancer-related death in elderly men worldwide. It arises from the glandular epithelial cells of the prostate, predominantly from the peripheral zone. The disease typically affects men over the age of 50 years, with incidence increasing sharply with advancing age.
Most prostate cancers are slow-growing, but a subset behaves aggressively, leading to local invasion, metastasis, and death. Early diagnosis through prostate-specific antigen (PSA) testing, digital rectal examination (DRE), and biopsy has significantly improved detection rates.
~Anatomy of the Prostate
The prostate is a fibromuscular gland located below the urinary bladder and surrounds the proximal urethra.
Zones of the Prostate
Peripheral zone – site of ~70% of carcinomas
Central zone
Transition zone – commonly involved in benign prostatic hyperplasia (BPH)
Anterior fibromuscular stroma
~Epidemiology
Most common cancer in men (excluding skin cancer)
Incidence increases after 50 years
More common in African-American men
Rare before age 40
High prevalence in Western countries
~Etiology and Risk Factors
Age
Strongest risk factor
Majority of cases occur after 65 years
Genetic Factors
Family history increases risk
Mutations in:
BRCA1 and BRCA2
HOXB13
Hormonal Factors
Androgen-dependent tumor
Testosterone and dihydrotestosterone (DHT) play a key role
Environmental and Lifestyle Factors
High-fat diet
Obesity
Smoking
Sedentary lifestyle
~Pathogenesis
Prostate adenocarcinoma develops through a sequence of molecular and histological changes.
Precursor Lesion
Prostatic Intraepithelial Neoplasia (PIN)
Especially high-grade PIN
Characterized by cellular atypia without stromal invasion
Molecular Changes
TMPRSS2-ERG gene fusion
PTEN tumor suppressor gene loss
Increased androgen receptor signaling
~Clinical Features
Early Stage
Often asymptomatic
Detected incidentally through PSA screening
Late Stage
Increased urinary frequency
Nocturia
Hesitancy
Weak urinary stream
Hematuria
Bone pain (due to metastasis)
Weight loss and fatigue
~Physical Examination
Digital Rectal Examination (DRE)
Hard, irregular, nodular prostate
Loss of normal median sulcus
Asymmetrical enlargement
~Gross Pathology
Firm, ill-defined gray-white areas
Usually located in the peripheral zone
Tumor may be multifocal
Advanced tumors invade seminal vesicles and bladder neck
~Histopathology
Microscopic Features
Small, crowded malignant glands
Infiltration into surrounding stroma
Loss of basal cell layer
Enlarged nuclei with prominent nucleoli
Perineural invasion (common)
~Gleason Grading System
The Gleason score is the most important prognostic factor.
Scoring
Based on glandular architecture
Two most common patterns graded from 1 to 5
Gleason score = Primary grade + Secondary grade
Risk Groups
Score ≤6: Low grade
Score 7: Intermediate grade
Score 8–10: High grade
~TNM Staging
Tumor (T)
T1: Clinically inapparent
T2: Confined to prostate
T3: Extraprostatic extension
T4: Invades adjacent structures
Node (N)
N0: No lymph node involvement
N1: Pelvic lymph node metastasis
Metastasis (M)
M0: No distant metastasis
M1: Distant metastasis (commonly bone)
~Patterns of Spread
Local Spread
Seminal vesicles
Bladder neck
Urethra
Lymphatic Spread
Pelvic lymph nodes
Obturator and iliac nodes
Hematogenous Spread
Bones (vertebrae, pelvis, ribs)
Produces osteoblastic lesions
~Diagnosis
Laboratory Investigations
Elevated PSA
PSA velocity and PSA density
Imaging
Transrectal ultrasound (TRUS)
MRI prostate
Bone scan for metastasis
Biopsy
TRUS-guided core needle biopsy
Gold standard for diagnosis
~Differential Diagnosis
Benign prostatic hyperplasia (BPH)
Prostatitis
Prostatic intraepithelial neoplasia
Small cell carcinoma of prostate
~Treatment
Localized Disease
Radical prostatectomy
Radiation therapy (external beam or brachytherapy)
Active surveillance in low-risk cases
Advanced Disease
Androgen deprivation therapy (ADT)
Orchiectomy
Anti-androgens (bicalutamide)
Chemotherapy (docetaxel)
Metastatic Disease
Hormonal therapy
Palliative radiotherapy
Bone-targeted therapy (bisphosphonates)
~Prognosis
Prognosis depends on:
Gleason score
PSA level
Tumor stage
Lymph node involvement
Survival Rates
Localized disease: Excellent prognosis
Advanced disease: Poorer outcomes
~Prevention and Screening
PSA screening (controversial but useful)
Healthy diet
Regular physical activity
Genetic counseling in high-risk individuals
~Complications
Urinary incontinence
Erectile dysfunction
Bone fractures
Metastatic pain
Hormonal therapy side effects
~Conclusion
Prostate adenocarcinoma is a common malignancy of aging men with a wide spectrum of clinical behavior. Early detection through PSA testing and biopsy allows curative treatment in localized disease, while advanced stages require systemic therapy. Understanding the pathology, grading, staging, and treatment options is essential for effective management and improved patient outcomes.
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