Key Facts

Prostate cancer is the most commonly diagnosed cancer in men in the UK. It has a wide clinical spectrum, from indolent low-grade disease requiring only surveillance to aggressive high-grade disease requiring multimodal treatment. Risk stratification guides management decisions.

Epidemiology

Approximately 52,000 new cases diagnosed annually in the UK. Lifetime risk is 1 in 8 for UK men. Incidence increases with age — median age at diagnosis is 72 years. Afro-Caribbean men have approximately 2-3 times higher risk. It is the second most common cause of male cancer death.

Aetiology

• Age: Strongest risk factor — rare before 50, incidence rises steeply with age
• Ethnicity: Afro-Caribbean > Caucasian > Asian
• Family history: First-degree relative doubles risk; BRCA2 mutation increases risk ~5-fold
• Genetics: BRCA2, HOXB13, Lynch syndrome
• Diet: Possible associations with high-fat Western diet (evidence mixed)

Pathophysiology

Prostate adenocarcinoma arises predominantly from the peripheral zone (70%) — hence palpable on DRE. It is androgen-dependent, driven by testosterone conversion to dihydrotestosterone (DHT) via 5-alpha-reductase. The androgen receptor signalling pathway is the primary therapeutic target. Metastasis is predominantly to bone (osteosclerotic), lymph nodes, and less commonly lung and liver.

Early Disease

• Often asymptomatic — detected by raised PSA
• Incidental finding on TURP histology
• Hard, irregular prostate on DRE (advanced local disease)

Locally Advanced Disease

• LUTS (voiding and storage symptoms)
• Haematuria, haematospermia
• Erectile dysfunction
• Pelvic pain

Metastatic Disease

• Bone pain (especially lower back, pelvis, femora)
• Pathological fractures
• Spinal cord compression (emergency)
• Weight loss, fatigue, anaemia
• Ureteric obstruction (bilateral hydronephrosis)

Red Flags

• New back pain in elderly man with raised PSA — investigate for bone metastases
• Bilateral leg weakness with urinary retention — spinal cord compression (emergency MRI and dexamethasone)
• Rapidly rising PSA (doubling time <3 months) — aggressive disease
• ALP significantly raised with normal LFTs — bone metastases

Bedside

• DRE (digital rectal examination): Hard, irregular prostate suggests cancer; normal DRE does not exclude it
• Urinalysis: Exclude UTI before PSA testing

Bloods

• PSA: Age-adjusted thresholds; >4 ng/mL generally warrants further investigation
• Free:total PSA ratio: <15% more suggestive of cancer
• FBC: Anaemia in metastatic disease
• ALP: Raised in bone metastases
• U&Es: Renal function — bilateral obstruction

Imaging

• mpMRI pelvis: First-line per NICE NG131 — PI-RADS score (1-5); biopsy recommended if PI-RADS ≥3
• TRUS biopsy or transperineal biopsy: Guided by MRI findings (12 systematic + targeted cores)
• CT thorax/abdomen/pelvis: Staging for intermediate/high-risk disease
• Bone scan (isotope): Detect bone metastases (if PSA >20 or Gleason ≥8)
• PSMA PET-CT: Increasingly used for staging and detecting recurrence

Special Tests

• Genomic tests: Oncotype DX, Prolaris — help risk stratify borderline cases
• MRI-targeted biopsy: Superior to systematic biopsy alone (PROMIS and PRECISION trials)

Non-pharmacological

• Active surveillance: Low-risk disease (Gleason 3+3, PSA <10, T1-T2a); serial PSA, mpMRI, re-biopsy
• Watchful waiting: For older/comorbid men with limited life expectancy — treat symptoms only
• Lifestyle: Maintain healthy weight, regular exercise

Pharmacological

• LHRH agonists: Goserelin 3.6mg SC monthly or leuprorelin 3.75mg IM monthly — medical castration
• LHRH antagonist: Degarelix 240mg SC loading then 80mg monthly — no testosterone flare
• Anti-androgens: Bicalutamide 50mg OD (with LHRH agonist to prevent flare) or 150mg OD as monotherapy
• Abiraterone 1000mg OD + prednisolone 5mg OD: For metastatic/castration-resistant disease (STAMPEDE, LATITUDE trials)
• Enzalutamide 160mg OD: Androgen receptor inhibitor — castration-resistant prostate cancer (PREVAIL, PROSPER trials)
• Docetaxel chemotherapy: 75mg/m² 3-weekly — for metastatic castration-resistant disease (TAX327 trial) or upfront with ADT (STAMPEDE)

Surgical/Interventional

• Radical prostatectomy: Robot-assisted laparoscopic or open — curative for localised/locally advanced disease
• Radical radiotherapy: External beam (IMRT/VMAT) ± brachytherapy boost — curative alternative
• ADT + radiotherapy: Standard for high-risk localised/locally advanced disease
• TURP: Palliative — for bladder outflow obstruction
• Spinal cord compression: Emergency dexamethasone 16mg IV + urgent MRI + oncology referral

Referral Criteria

• Raised PSA or abnormal DRE — 2WW urology referral
• Confirmed prostate cancer — specialist MDT discussion
• Spinal cord compression — emergency oncology/neurosurgery referral
• Bone pain with raised PSA — urgent investigation

• Localised low-risk: 10-year cancer-specific survival >98% (ProtecT trial — similar outcomes for surveillance, surgery, and radiotherapy at 10 years)
• Localised intermediate-risk: 10-year cancer-specific survival >90% with radical treatment
• Locally advanced: 5-year survival 85-95% with combined ADT + radiotherapy
• Metastatic hormone-sensitive: Median survival 4-6 years with ADT + abiraterone/docetaxel
• Metastatic castration-resistant: Median survival 15-30 months depending on treatment

ISUP Grade Groups

Risk Stratification (NICE NG131)

Landmark Trials