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.