Prostate — Zones, BPH vs Carcinoma, Gleason Grade Groups and PSA

The prostate is a dense fibromuscular gland shaped like an inverted cone: the base lies against the neck of the urinary bladder and the apex rests on the external urethral sphincter. It sits in the lesser pelvis, wrapping around the proximal urethra, and is enclosed in a fibrous capsule with its nerves and vascular plexus, which is in turn surrounded by a visceral layer of pelvic fascia.

The gland is also traversed by the proximal urethra and the two ejaculatory ducts, which enter as they emerge from the seminal vesicles and converge on the urethra at the seminal colliculus (verumontanum). Embryologically the prostate develops as epithelial buds growing from the wall of the urogenital sinus; the buds branch, canalise and form ducts and acini, while the surrounding mesenchyme forms the stroma and smooth muscle. See development of the genitourinary system.

Many anatomy textbooks describe five lobes — anterior, posterior, two lateral and a median lobe — while clinicians speak of two lateral lobes and a median lobe. The histologically based zonal description is the one that matters for pathology.

• Arteries: the inferior vesical artery is the major supply, with branches from the middle rectal and internal pudendal arteries.
• Veins: the prostatic venous plexus drains to the internal iliac veins.
• Lymphatics: internal iliac and sacral nodes.
• Nerves: autonomic fibres from the inferior hypogastric plexus — sympathetic input via the hypogastric nerve and parasympathetic input via the pelvic nerve; both plexuses carry sensory fibres.

BPH is non-malignant proliferation of prostatic tissue and a common cause of lower urinary tract symptoms (LUTS) in older men. Histologically it is a hyperplastic process with increased numbers of both glandular and stromal cells in the periurethral and transition zones: the periurethral zone shows hyperplastic stromal nodules and the transition zone shows glandular nodular proliferation. The enlargement is nodular, not diffuse.

• Mechanism: a loss of balance between cell proliferation and apoptosis favours proliferation.
• Androgens: testicular androgens are required. DHT drives growth, and testosterone is converted to DHT by 5-alpha-reductase type 2 in stromal cells, which accounts for about 90% of total intraprostatic androgens.
• Static component: increased gland volume. Dynamic component: prostatic smooth muscle tone — the reason alpha-blockers relax the gland and 5-alpha-reductase inhibitors shrink it.
• Risk factors: age (about half of men over 50 show evidence of BPH), metabolic syndrome and obesity (higher prostate volumes), diabetes and insulin use, and chronic inflammation.
• BPH is not a risk factor for prostate cancer, although it can raise PSA.

LUTS divide into storage symptoms (frequency, nocturia, urgency) and voiding symptoms (weak or intermittent stream, hesitancy, straining, prolonged micturition, incomplete emptying). BPH accounts for more than two-thirds of cases of acute urinary retention. Diuretics for hypertension or heart failure can worsen frequency and nocturia.

Severe BPH that has failed medical therapy, or recurrent retention, is treated surgically, classically by transurethral resection of the prostate (TURP): an instrument is passed up the urethra and trims tissue to enlarge the channel. Starting a 5-ARI 2 to 4 weeks before surgery reduces bleeding. See adrenergic drugs for the receptor pharmacology.

Prostate cancer is usually an adenocarcinoma, arising in glandular tissue, most often in the peripheral zone. Most tumours grow slowly, are low-grade and cause no early symptoms; late features include bone pain, anaemia, spinal cord compression and renal failure from bilateral ureteric obstruction. Metastatic disease often causes severe bone pain in the vertebrae, pelvis, hips and ribs. Risk factors include family history, higher BMI, smoking, BRCA2 mutation (BRCA1 to a lesser degree) and over 100 other variants.

Up to 14% of patients have metastatic disease at diagnosis. Prostatic MRI with PI-RADS scoring and MRI-guided biopsy are now standard, and PSMA PET is emerging as the leading imaging modality for staging because PSMA is over-expressed in 90% to 100% of prostate cancer cells. F-18 sodium fluoride PET is a sensitive tracer for skeletal metastases. See renal tumours and neoplasia nomenclature for related pathology.

The Gleason system grades prostate cancer by the architecture of the glands, not by individual cell features. Patterns are graded 1 to 5. The score is the sum of the most common (primary) pattern and the second most common pattern, so a tumour is reported as, for example, 3+4 = 7. If only one pattern is seen it is doubled (3+3 = 6, the commonest score). The primary pattern comes first: 3+4 and 4+3 are different.

Prostate-specific antigen is a serine protease produced by the columnar epithelium of prostatic tissue. Its physiological job is to break down semenogelin and fibronectin, which reduces seminal viscosity (liquefies the ejaculate) and so assists sperm migration. PSA is organ-specific, not cancer-specific: BPH, prostatitis and other causes also raise it.

Screening is controversial because of overdiagnosis and overtreatment, but most professional bodies endorse informed PSA screening; see screening tests for how sensitivity and specificity apply.