Prostate cancer
Exam Tips
- In OSCE/viva, state clearly that early prostate cancer is often asymptomatic; symptoms do not reliably exclude significant disease.
- Use the triad for risk stratification: PSA + Grade Group + clinical TNM, then map to Cambridge Prognostic Group for prognostic discussion.
- Differentiate localised, locally advanced, and metastatic disease because management intent (surveillance/curative/palliative-systemic) changes fundamentally.
- Mention safety explicitly: anti-androgen flare cover with GnRH agonists, and urgent dexamethasone plus same-day oncology/spinal pathway referral if cord compression is suspected.
- For pathology stations, remember biopsy usually samples multiple cores and grading now uses ISUP Grade Groups rather than reporting Gleason alone.
- Image reference for revision: see a standard TNM prostate staging diagram and Grade Group histology plate in your core urology text/lecture pack (for example the staging figure in the prostate cancer chapter).
Definition
Prostate cancer is a malignant neoplasm of the prostate gland, and in clinical practice around 95% are adenocarcinomas arising from glandular epithelium. It is commonly multifocal and biologically heterogeneous, with many tumours remaining indolent for years while a smaller subgroup behaves aggressively with extracapsular spread and distant metastasis, most often to bone.
Pathophysiology
Most prostate cancers develop in an androgen-responsive environment, typically in the peripheral zone, through accumulation of genomic alterations (including hereditary susceptibility in some patients, such as BRCA2/HOXB13-associated risk). Tumour clones can differ within the same prostate, explaining variable behaviour from low-risk organ-confined disease to rapidly progressive cancer. Progression involves local invasion beyond the prostatic capsule (for example seminal vesicles/bladder neck) and metastatic dissemination via lymphatic and haematogenous routes, with osteoblastic-predominant bone metastases causing pain and fragility fractures. Advanced disease may evolve into castration-resistant prostate cancer through adaptive androgen-receptor pathway signalling despite castrate testosterone levels.
Risk Factors
- Increasing age (risk rises substantially from age 50; commonest diagnosis 65-69 years)
- Black ethnicity (higher incidence and mortality than White men in UK cohorts)
- Family history in first-degree relatives (especially multiple affected relatives or affected brother)
- Inherited cancer-predisposition variants (for example BRCA1/2, HOXB13)
- Presence of a prostate in trans women after gender-affirming surgery (risk persists, though population incidence is uncertain)
Clinical Features
Symptoms
- Often asymptomatic in early or even locally advanced disease
- Lower urinary tract symptoms: hesitancy, weak stream, frequency, nocturia, incomplete emptying
- Visible or non-visible haematuria, occasionally haematospermia
- Erectile dysfunction or painful ejaculation in some patients
- Metastatic features: persistent bone pain (especially back/pelvis), unintentional weight loss, fatigue
- Red-flag metastatic spinal cord compression symptoms: back pain with limb weakness, sensory change, bladder/bowel dysfunction
Signs
- Digital rectal examination may show a hard, irregular, nodular, or asymmetric prostate
- Prostate may be enlarged but malignant disease can coexist with a near-normal-sized gland
- Bony tenderness in metastatic disease
- Neurological deficits if spinal cord/cauda equina compromise occurs
- Cachexia or pallor in advanced disease
Investigations
Management
Lifestyle Modifications
- Shared decision-making using stage, PSA, Grade Group, Cambridge Prognostic Group, comorbidity, and patient priorities
- Exercise, weight optimisation, smoking cessation, and cardiovascular risk reduction (important during androgen deprivation)
- Bone health strategy during long-term androgen deprivation (calcium/vitamin D intake, fracture-risk assessment, resistance exercise)
- Safety-net advice for urgent symptoms (especially possible spinal cord compression or acute urinary retention)
Pharmacological Treatment
Androgen deprivation therapy (ADT)
- Goserelin implant 3.6 mg subcut every 28 days (or 10.8 mg every 12 weeks)
- Leuprorelin 3.75 mg IM/SC monthly (or 11.25 mg every 3 months, product-dependent)
- Triptorelin 3 mg IM monthly (or longer-acting depot preparations)
- Degarelix 240 mg loading dose SC, then 80 mg SC monthly
Core systemic treatment for advanced/metastatic disease. With GnRH agonists (goserelin/leuprorelin/triptorelin), give short-course anti-androgen flare protection (for example bicalutamide 50 mg once daily starting before first injection) in patients at risk of flare complications. Monitor for hot flushes, metabolic syndrome, diabetes risk, QT prolongation, depression, and osteoporosis.
Androgen receptor pathway intensification
- Abiraterone 1000 mg once daily on empty stomach plus prednisolone 5 mg once daily
- Enzalutamide 160 mg once daily
- Apalutamide 240 mg once daily
Used in selected metastatic hormone-sensitive or castration-resistant settings with specialist oncology input. Key safety issues: abiraterone can cause hypertension, hypokalaemia, fluid retention, and hepatotoxicity (monitor BP, potassium, LFTs); enzalutamide/apalutamide may increase seizure/fall risk and interact with other medicines.
Chemotherapy (specialist oncology)
- Docetaxel 75 mg/m^2 IV every 3 weeks with prednisolone (commonly 5 mg twice daily in prostate regimens)
Consider in fit patients with metastatic disease depending on line of therapy. Major warnings: neutropenic sepsis risk, neuropathy, hypersensitivity, and fluid retention; requires full counselling and blood count monitoring.
Supportive and complication-directed medicines
- Dexamethasone 8 mg twice daily urgently if metastatic spinal cord compression is suspected
- Zoledronic acid IV (dose adjusted to renal function) or denosumab 120 mg SC every 4 weeks for selected bone metastatic disease
Do not delay emergency referral for neurological compromise. For bone-modifying agents, check dental status first because of osteonecrosis of the jaw risk; monitor calcium and renal function.
Surgical / Interventional
- Active surveillance for suitable low-risk localised disease (protocolled PSA/MRI/biopsy follow-up)
- Radical prostatectomy with pelvic lymph node dissection in selected localised/locally advanced cases
- Radical radiotherapy (external beam, with or without brachytherapy) usually combined with ADT by risk group
- Palliative procedures where needed: TURP for obstruction, nephrostomy/stenting for upper tract obstruction, orthopaedic/radiotherapy interventions for painful bone metastases
Complications
- Metastatic bone pain and pathological fractures
- Metastatic spinal cord compression (oncological emergency)
- Urinary retention or obstructive uropathy with renal impairment
- Treatment-related complications: erectile dysfunction and urinary incontinence after radical treatment
- ADT-related osteoporosis, cardiovascular/metabolic toxicity, and mood/cognitive effects
Prognosis
Outcome is highly stage- and biology-dependent. Many localised cancers are slow growing, whereas higher PSA, higher Grade Group, and more advanced TNM stage predict worse survival; Cambridge Prognostic Group 10-year prostate-cancer mortality rises from about 1.9% (CPG1) to about 31.9% (CPG5). Metastatic disease has substantially poorer outcomes (around half survive 5 years), though modern systemic therapy has improved disease control in many patients.
Sources & References
🏥BMJ Best Practice(4)
💊BNF Drug References(18)
- Abiraterone acetate[management.pharmacological]
- Apalutamide[management.pharmacological]
- Bicalutamide[management.pharmacological]
- Cabazitaxel [Specialist drug][management.pharmacological]
- Darolutamide[management.pharmacological]
- Degarelix[management.pharmacological]
- Diethylstilbestrol[management.pharmacological]
- Enzalutamide[management.pharmacological]
- Estramustine phosphate [Specialist drug][management.pharmacological]
- Flutamide[management.pharmacological]
- Leuprorelin acetate[management.pharmacological]
- Olaparib [Specialist drug][management.pharmacological]
- Relugolix[management.pharmacological]
- Talazoparib [Specialist drug][management.pharmacological]
- Testosterone[contraindications]
- Testosterone enantate[contraindications]
- Testosterone propionate[contraindications]
- Testosterone undecanoate[contraindications]
✅NICE Guidelines(1)
- Prostate cancer[overview]
📖Textbook References(1)
- [Williams, Bailey and Love's Short Practice of Surgery] Norman Williams, Christopher Bulstrode, P Ronan O'Connell - Bailey & Love's Short Practice of Surgery 26E (2013, CRC Press) - libgen.li.pdf(pp. 159)[context]