Makindo Medical Notes

Related Subjects: | Urothelial Tumours | Haematuria | Acute Urinary Retention | Anuria and Oliguria | Bladder Cancer | Renal Cell Carcinoma | Benign Prostatic Hyperplasia | IgA Nephropathy | Prostate Cancer | Henoch-Schonlein Purpura | Glomerulonephritis

PSA (Prostate-Specific Antigen) is elevated in various prostate diseases. PSA velocity measures the rate of PSA change over time. A PSA > 100 ng/mL usually indicates bony involvement. Rectal examination does not significantly raise PSA levels. PSA is a 34 KDa glycoprotein protease secreted by epithelial cells lining the prostate's acini, responsible for liquefying semen. Elevated PSA can be associated with prostate carcinoma, BPH, aging, post-ejaculation, and prostate calculi.

About Prostate Cancer

• Often detected post-mortem in individuals over 70 years old.
• Key challenge: deciding when to screen and treat.
• Screening has not been proven to improve survival outcomes.
• Prostate cancer is testosterone-dependent.

Epidemiology

• UK: 41,700 new diagnoses annually.
• Only 1% of cases are diagnosed in patients under 50 years old.
• More common in patients of black African or Caribbean descent.
• Family history: a first-degree relative with prostate cancer increases the risk 3.5 times.
• Smoking and obesity are associated with increased risk of fatal prostate cancer.

Pathology

• 95% of cases are acinar adenocarcinomas arising from glandular epithelial cells.
• 5% are squamous, transitional, or other rare forms.
• Most cancers originate in the peripheral zone of the prostate gland.
• Prostate intraepithelial neoplasia (PIN) is considered a precursor to prostate cancer.
• Prostate epithelial cells produce PSA and acid phosphatase.

Clinical Presentation

• Lower urinary tract symptoms (LUTS): increased frequency, nocturia, weak stream, and dribbling.
• Bone pain or fractures indicate metastatic disease.

Common Presentations

• Elevated PSA levels detected through screening or incidentally post-TURP histology.
• Hard, craggy prostate with loss of the midline sulcus on digital rectal examination (DRE).
• Bladder outflow obstruction: weak stream, nocturia.
• Secondary renal problems.
• Late-stage disease may present with bone pain and osteosclerotic metastases visible on X-ray or bone scan.
• Advanced disease: haematospermia, haematuria, and urinary obstruction.

Prostate-Specific Antigen (PSA) Levels

• Normal PSA for men under 50: <3 ng/mL.
• Normal PSA for men aged 60-69: <4 ng/mL.
• Normal PSA for men over 70: <5 ng/mL.
• A PSA <10 ng/mL is commonly associated with benign prostatic hyperplasia (BPH) or chronic inflammation, with only 20% testing positive for cancer.
• The likelihood of malignancy rises to 50% with a PSA >10 ng/mL.

Investigations

• U&E: to assess renal function; raised ALP suggests bony metastases.
• FBC: may show leucoerythroblastic anaemia.
• PSA > 4 ng/mL: malignancy in 40% of biopsies.
• PSA > 10 ng/mL: malignancy in 60% of biopsies.
• Transrectal ultrasound (TRUS)-guided prostate biopsy.
• Bone scan if PSA > 20 ng/mL or if bone pain is present to check for metastases (note: Paget's disease, healing fractures, and arthritis can produce false positives).
• Many urologists now recommend multi-parametric MRI (MP-MRI) prior to considering prostate biopsy.
• The Gleason grading system is used to assess tumour aggressiveness.

Risk Stratification for Localized Prostate Cancer
Level of Risk	PSA	Gleason Score	Clinical Stage
Low	<10 ng/mL	=6	T1-T2a
Intermediate	10-20 ng/mL	7	T2b
High	>20 ng/mL	8-10	=T2c

Management of Localized Disease

• Radical retropubic prostatectomy: aims to remove all diseased tissue while preserving continence and avoiding impotence. Suggested for patients with >10 years life expectancy.
• Radiation therapy: external beam or brachytherapy (radioactive seed implantation). Diarrhoea and urinary frequency are common side effects, and urethral strictures may occur.
• Watchful waiting: reasonable for older men with well-differentiated tumours. Many patients die from unrelated causes.
• Side effects of treatment: impotence, incontinence, bowel dysfunction.

Management of Metastatic Disease

• Androgen deprivation therapy (ADT): blocks androgen action or decreases androgen production via medical or surgical methods.
• Ketoconazole: blocks androgen production.
• GnRH analogues: initially raise FSH and LH, causing a temporary rise in testosterone (flare), followed by downregulation of receptors. The flare should be avoided in patients with spinal cord or obstructive lesions.
• Anti-androgens (e.g., flutamide): given to block the effects of the testosterone flare along with GnRH analogues.
• Surgical orchidectomy: can cause side effects such as hot flushes, fatigue, impotence, and loss of muscle mass.