Key Facts

Prostate cancer has a wide spectrum of biological behaviour, from indolent disease requiring only monitoring to aggressive metastatic disease. Understanding risk stratification and appropriate treatment selection is crucial.

Epidemiology

• UK incidence: approximately 52,300 new cases per year (most common cancer in men)
• Mortality: approximately 12,000 deaths per year (2nd most common cause of cancer death in men)
• Peak incidence: 75-79 years
• Lifetime risk: 1 in 8 men
• 5-year survival: approximately 87% overall; >95% for localised disease

Aetiology

• Age: strongest risk factor; rare before 50; median age at diagnosis 72
• Ethnicity: Black men have 2× higher risk; earlier onset
• Family history: first-degree relative with prostate cancer doubles risk; BRCA2 carriers 3-5× risk
• Genetic: BRCA2, HOXB13, Lynch syndrome
• Protective: 5-alpha reductase inhibitors (finasteride, dutasteride) reduce incidence by 25% but may select for higher-grade tumours

Pathophysiology

• Adenocarcinoma (>95%): arises from prostatic epithelial cells, typically in the peripheral zone
• Androgen-dependent growth (testosterone → DHT via 5-alpha reductase → AR activation)
• Multifocal in approximately 85% of cases
• Spread: local invasion (seminal vesicles, bladder) → lymphatic (pelvic/para-aortic) → haematogenous (bone: sclerotic metastases; liver, lung)
• Castration-resistant prostate cancer (CRPC): disease progresses despite castrate testosterone levels; may still be AR-driven

Early Disease (Often Asymptomatic)

• Detected on PSA testing or incidental finding
• May have LUTS (frequency, hesitancy, nocturia) but these more commonly due to BPH
• Hard, irregular nodule on DRE

Locally Advanced Disease

• Haematuria, haematospermia
• Obstructive symptoms: acute urinary retention
• Perineal pain
• Erectile dysfunction
• Lower limb oedema (lymphatic/venous obstruction)

Metastatic Disease

• Bone pain (axial skeleton; sclerotic metastases)
• Pathological fractures
• Spinal cord compression
• Weight loss, fatigue, anorexia
• Anaemia

Red Flags

• Hard irregular prostate on DRE
• Rapidly rising PSA (PSA velocity >0.75 ng/mL/year)
• New bone pain with raised PSA
• Lower limb weakness in man with prostate cancer (MSCC)
• PSA >100 ng/mL (almost always metastatic)

Bedside

• Digital rectal examination (DRE): assess prostate size, shape, consistency, nodules
• Urinalysis (exclude UTI)

Bloods

• PSA: age-adjusted reference ranges (50-59: <3, 60-69: <4, >70: <5 ng/mL); also check if symptoms or abnormal DRE
• FBC (anaemia in advanced disease)
• U&Es, ALP (bone metastases), LDH

Imaging

• mpMRI prostate: first-line before biopsy (NICE NG131); PI-RADS 1-2 (negative) avoids biopsy; PI-RADS 3-5 → targeted biopsy
• TRUS biopsy or MRI-targeted transperineal biopsy: histological diagnosis; at least 12 cores
• CT chest/abdomen/pelvis and bone scan: staging for intermediate/high-risk disease
• PSMA PET-CT: superior staging for high-risk disease; detects small volume metastases

Special Tests

• Gleason grading: pathologist grades tumour architecture (Grade Groups 1-5)
• Genomic tests: Oncotype DX GPS, Prolaris (risk stratification for active surveillance candidates)
• BRCA2/ATM testing: for metastatic disease (PARP inhibitor eligibility)
• Bone density (DEXA): before long-term ADT

Non-pharmacological

• Active surveillance: for low-risk disease (Grade Group 1, PSA <10, ≤T2a); regular PSA, mpMRI, and re-biopsy; ProtecT trial supports safety
• Watchful waiting: for men with limited life expectancy; treat symptoms only

Pharmacological

• Androgen deprivation therapy (ADT):
  • GnRH agonists: goserelin 3.6mg SC monthly or 10.8mg 3-monthly; triptorelin, leuprorelin
  • GnRH antagonist: degarelix 240mg SC loading → 80mg monthly (no testosterone flare)
  • Anti-androgens: bicalutamide 50mg OD (combined androgen blockade) or 150mg monotherapy
• Radical RT ± ADT: EBRT (78 Gy in 39 fractions or hypofractionated) ± 6 months ADT (intermediate-risk) or 2-3 years ADT (high-risk; STAMPEDE trial)
• Metastatic hormone-sensitive prostate cancer (mHSPC):
  • ADT + docetaxel (STAMPEDE/CHAARTED) or
  • ADT + abiraterone 1000mg OD + prednisolone 5mg OD (STAMPEDE/LATITUDE) or
  • ADT + enzalutamide 160mg OD (ENZAMET) or
  • ADT + apalutamide (TITAN)
• Castration-resistant prostate cancer (CRPC):
  • Abiraterone + prednisolone (COU-AA-301/302)
  • Enzalutamide (PREVAIL/AFFIRM)
  • Docetaxel 75mg/m² 3-weekly
  • Cabazitaxel (post-docetaxel; TROPIC trial)
  • Olaparib (BRCA1/2 or ATM mutated; PROfound trial)
  • Lutetium-177 PSMA (PSMA-expressing; VISION trial)
  • Radium-223 (bone-only metastases; ALSYMPCA trial)

Surgical/Interventional

• Radical prostatectomy (open, laparoscopic, or robot-assisted): for localised disease; cure rate >90% for organ-confined disease
• Brachytherapy (low-dose rate or high-dose rate): alternative for low/intermediate risk
• Pelvic lymph node dissection: at time of radical prostatectomy for intermediate/high-risk
• TURP: for obstructive symptoms (palliative)
• Orchidectomy (bilateral): surgical castration; rapid, permanent; rarely performed now

Referral Criteria

• Abnormal DRE or raised PSA: urgent 2-week wait urology referral
• Confirmed prostate cancer: MDT discussion
• BRCA carrier or strong family history: genetics referral and early PSA screening (from age 40)
• Advanced disease: oncology referral

• Overall 5-year survival: 87% (one of the highest of any cancer)
• Localised disease: >95% 10-year survival with active surveillance, surgery, or RT (ProtecT trial)
• Locally advanced: 80-85% with multimodal treatment
• Metastatic hormone-sensitive: median survival 4-6 years with intensified treatment (ADT + docetaxel or abiraterone)
• Castration-resistant metastatic: median survival 2-3 years with modern sequential therapies
• Bone metastases: managed but significantly impacts QoL (pain, fractures, MSCC)

Risk Stratification (NICE NG131)

Key Prostate Cancer Trials