Prostate Cancer
Summary
Prostate cancer is the most common cancer in men. It is typically a slow-growing adenocarcinoma arising from the Peripheral Zone (70%) of the gland. Because of this location, it often does not cause urinary symptoms (LUTS) until very advanced, unlike BPH which affects the Transition Zone. Screening is controversial due to the lack of specificity of PSA, but modern diagnosis has been revolutionised by multiparametric MRI (mpMRI) before biopsy. Treatment ranges from Active Surveillance for low-risk disease to Radical Prostatectomy, Radiotherapy, or Androgen Deprivation Therapy (ADT) for advanced disease. [1,2]
Key Facts
- Gleason Score: The histological grading system. Two most common patterns are summed (e.g., 3+4 = 7).
- Grade Group 1: Gleason 6 (3+3). Indolent.
- Grade Group 2: Gleason 7 (3+4). Intermediate.
- Grade Group 5: Gleason 9-10. Highly aggressive.
- Bone Metastases: Prostate cancer spreads to the axial skeleton (spine/pelvis) causing Sclerotic (bone-forming) metastases, unlike the lytic lesions of breast/lung cancer.
- The "Flare": Starting LHRH agonists (Goserelin) initially stimulates Testosterone production before crashing it. This can cause tumor growth and spinal compression. Always cover with an Anti-androgen (Bicalutamide) for the first few weeks.
Clinical Pearls
PSA Rules:
- Don't measure if: UTI (wait 6 weeks), Ejaculation (wait 48h), Vigorous exercise/Cycling (wait 48h), or recently catheterised.
- DRE Effect: Usually negligible, but vigorous massage can raise it.
One Stop Shop: The PROMIS trial showed that mpMRI is an excellent triage test. If MRI is PIRADS 1-2 (normal), 27% of men can avoid a painful biopsy safely.
LUTS vs Cancer: A man with urinary flow symptoms usually has BPH. A man with no symptoms but a hard prostate has cancer. Cancer is silent.
Incidence
- 1 in 8 men will get prostate cancer.
- Increases with age (autopsy studies show incident cancer in 80% of 80 year olds).
Risk Factors
- Age: Strongest factor.
- Ethnicity: Black African/Caribbean men have 2-3x higher risk and present younger/more aggressively. PSA thresholds should be lower (2.5) for Black men aged 45+.
- Family History: BRCA2 mutation carriers. First degree relative.
Anatomy
- Zone: Peripheral Zone (Posterior, felt on DRE).
- Driver: Testosterone dependent.
- Spread:
- Local: Seminal vesicles, Bladder neck, Rectum (rare due to Denonvilliers' fascia).
- Lymphatic: Obturator/Iliac nodes.
- Haematogenous: Bone (Batson's Venous Plexus -> Vertebrae).
Localised Disease
Advanced/Metastatic
Digital Rectal Examination (DRE)
- Normal: Walnut size, smooth, firm elastomere consistency, distinct median sulcus.
- Malignant: Hard/Woody nodule, Craggy, Asymmetrical, Loss of median sulcus.
PSA (Prostate Specific Antigen)
- Normal Limits: Age dependent.
- 50-59: less than 3.0
- 60-69: less than 4.0
- >70: less than 5.0
- False Positives: UTI, Prostatitis, BPH, Retention, Instrumentation.
Imaging
- mpMRI Prostate: Done BEFORE biopsy.
- Scoring: PI-RADS (Prostate Imaging Reporting and Data System) 1 to 5.
- PIRADS 4/5: Mandates biopsy.
- PIRADS 1/2: Consider discharge if PSA density low.
Diagnosis
- Transperineal Biopsy: Needle through perineum skin (under LA or GA). Lower sepsis risk than old TRUS (Transrectal) method.
- Bone Scan: Isotope scan for metastases (Hot spots).
- PSMA PET: Superior sensitivity for micrometastases.
Management Algorithm
PROSTATE CANCER DIAGNOSED
↓
RISK STRATIFY
(Gleason + PSA + Stage T1-T4)
↓
┌─────────────┼──────────────┐
LOW RISK INTERMEDIATE HIGH / METASTANDING
(Gleason 6) (Gleason 7) (Gleason 8-10, M1)
↓ ↓ ↓
ACTIVE RADICAL SYSTEMIC THERAPY
SURVEILLANCE SURGERY or (ADT)
RADIOTHERAPY +/- CHEMO
1. Localised Disease
- Active Surveillance: Monitor PSA/MRI/Biopsy. Treat only if it progresses. (Avoids side effects of treatment).
- Radical Prostatectomy: Robot-Assisted Laparoscopic Prostatectomy (RALP). Risk of ED and Incontinence.
- Radical Radiotherapy (EBRT): External beam.
- Brachytherapy: Radioactive seeds implanted.
2. Metastatic / Advanced Disease
- Mainstay: Androgen Deprivation Therapy (ADT).
- LHRH Agonists: Goserelin (Zoladex), Leuprorelin (Prostap). Must cover flare with Bicalutamide.
- LHRH Antagonists: Degarelix (No flare).
- Orchidectomy: Surgical castration (Gold standard, but psycholgically difficult).
- New Agents: Enzalutamide / Abiraterone (for hormone sensitive or resistant disease).
- Chemotherapy: Docetaxel (STAMPEDE trial).
3. Emergency: Cord Compression
- Urgent MRI Spine.
- Dexamethasone.
- Degarelix (Rapid ADT).
- Neurosurgery / Radiotherapy.
- Treatment Related:
- Surgery: Erectile Dysfunction (ED) due to nerve damage. Stress Incontinence.
- Radiotherapy: Radiation Proctitis (bleeding PR), Cystitis.
- ADT: Hot flushes, Gynaecomastia, Osteoporosis, Weight gain, Loss of libido.
- Localised: 5-year survival ~100%. Many men die with prostate cancer, not of it.
- Metastatic: Median survival 4-5 years (improving with new agents).
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| NG131 | NICE (2019) | Offer mpMRI first line before biopsy. Discuss Active Surveillance for low risk. |
| Screening | NSC | No national screening program (PSA too non-specific). |
Landmark Trials
1. PROMIS (2017)
- Findings: mpMRI is highly sensitive (93%) compared to TRUS biopsy (48%).
- Impact: Established MRI-first pathway.
2. PROTECT (2016)
- Findings: No difference in 10-year survival between Surgery, Radiotherapy, and Active Monitoring for localised disease (though metastasis rate slightly higher in monitoring).
- Impact: Supports conservative management for low risk.
3. STAMPEDE (Ongoing)
- Findings: Adding Docetaxel or Abiraterone upfront to ADT improves survival in metastatic disease.
What is Prostate Cancer?
It is a cancer of the walnut-sized gland that produces semen fluid. It is very common in older men.
Is it dangerous?
It depends.
- "Pussycat" Cancer: Low grade (Gleason 6). Grows so slowly it might never cause you harm. We just watch it.
- "Tiger" Cancer: High grade. Needs aggressive treatment.
The Test (PSA)
PSA acts as a smoke alarm. It tells us something is happening in the prostate, but not what. It could be cancer, infection, or just a large gland. That's why we need an MRI scan to see the fire.
Treatment Side Effects
Removing the prostate can damage the delicate nerves for erections and the valve for urine control. Many men recover these functions, but some have long-term problems. We only operate if necessary.
Primary Sources
- NICE Guideline NG131. Prostate cancer: diagnosis and management. 2019.
- Ahmed HU, et al. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS). Lancet. 2017.
- Hamdy FC, et al. 10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer (ProtecT). N Engl J Med. 2016.
Common Exam Questions
- Urology: "Gleason 3+4 vs 4+3. Which is worse?"
- Answer: 4+3 (Grade Group 3). The primary pattern is the first number. Pattern 4 is aggressive.
- Emergency: "PSA 1000 + Back pain + Leg weakness. Action?"
- Answer: Suspect Cord Compression. Urgent MRI Spine.
- Pharmacology: "Mechanism of Goserelin?"
- Answer: GnRH (LHRH) Agonist. Causes initial stimulation (flare) then down-regulation of receptors.
- Radiology: "Type of bone mets?"
- Answer: Sclerotic (Osteoblastic).
Viva Points
- PSA Density: PSA divided by Prostate Volume. >0.15 suggests cancer (vs BPH where high PSA is just due to huge volume).
- Prostate Zones:
- Peripheral: Cancer (70%).
- Transition: BPH.
- Central: Rare cancers.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.