Prostate Cancer
NICE guideline [NG131] Prostate cancer: diagnosis and management. Last updated: Dec 2021.
NICE guideline [NG12] Suspected cancer: recognition and referral. 1.6 Urological cancers. Last updated: May 2025.
NICE CKS Prostate cancer. Last revised: Aug 2025.
NICE BNF Treatment summaries Prostate cancer.
Background Information
Epidemiology
Prostate cancer is the most common type of cancer in men in the UK
- 1 in 6–8 men in the UK will get prostate cancer at some point in their lives
- Prostate cancer is also the second most common cause of cancer death in males in the UK (after lung cancer)
Histology
95% of prostate cancers are adenocarcinomas
Aetiology
The exact aetiology is unknown. Prostate cancer arises through androgen-dependent (testosterone and DHT) proliferation of genetically altered epithelial cells in the prostate
Risk factors:
- Age – strongest risk factor
- Most common age of diagnosis: 65-69 y/o
- >50% cases are in >70 y/o
- Incidence of disease is highest in >90 y/o
- Black ethnicity (higher risk of prostate cancer, and more likely to have metastatic cancer at diagnosis)
- Family history
- Germline mutation
- BRCA1/2
- HOXB13
Anatomy
Clinical points:
- BPH affects mainly the transition zone
- Prostate cancer affects mainly the peripheral zone
Anatomy of prostate zones:
| Prostate Zone | Location | % of prostate volume |
|---|---|---|
| Peripheral | Posterior & lateral aspects (the part that is palpable on ) | ~70% |
| Transition | Surrounds the proximal prostatic urethra | ~5–10% |
| Central | Surrounds the ejaculatory ducts | ~20–25% |
| Anterior fibromuscular stroma | Anterior aspect (non-glandular) | Minimal glandular tissue |
Diagnosis
Clinical Features
Most patients with prostate cancer are asymptomatic.
If symptoms are present, they depend on the extent of local invasion or metastatic disease:
| Constitutional symptoms |
|
| Local invasion |
|
| Metastasis | Most common site: bone metastasis
|
Red Flags and Referral
NICE recommends considering a DRE and PSA test in those with:
- Any LUTS, or
- Erectile dysfunction, or
- Visible haematuria
When to refer:
- Abnormal DRE (see below for suggestive features of malignancy), or
- Prostate cancer is suspected (based on symptoms) and ↑ PSA levels (above the age-specific thresholds – see below)
DRE (Digital Rectal Examination)
| DRE finding | BPH | Prostate cancer |
|---|---|---|
| Prostate size | Symmetrically enlarged | Normal / asymmetrically enlarged |
| Consistency / texture | Smooth, rubbery | Hard, firm, stony |
| Surface | Regular | Irregular, nodular |
| Median sulcus | Preserved | May be obliterated |
Prostate tenderness is suggestive of prostatitis; BPH and prostate cancer do not typically cause tenderness.
Note that a prostate gland that feels normal does NOT exclude prostate cancer.
PSA (Prostate Specific Antigen)
Age-specific PSA thresholds:
| Age (years) | PSA threshold (micrograms/litre) |
|---|---|
| Below 40 | Use clinical judgement |
| 40 to 49 | >2.5 |
| 50 to 59 | >3.5 |
| 60 to 69 | >4.5 |
| 70 to 79 | >6.5 |
| Above 79 | Use clinical judgement |
Information about PSA testing:
| Description | PSA is a protein produced by the prostate gland:
The aim of PSA testing is to detect early prostate cancer when treatment can be offered that may cure cancer or extend life. |
| Indications | Any of the following:
Before offering PSA testing, provide appropriate information and advice to enable the person to make an informed choice about testing |
| Interpretation | Normal PSA level: 0-4 micrograms/L
However, the normal upper limit varies according to age (and race) |
| Limitations |
There is a particular risk of over-diagnosing and overtreating prostatic cancer in >79 y/o men, where the prevalence is highest, but the proportion of cancers which are clinically significant is lowest PSA levels may be increased by the following conditions:
|
| Precautions before PSA testing | Before a PSA test, the patient should NOT have:
The above factors can raise the PSA and therefore give a false-positive result. Apart from those, BPH and advancing age also increase PSA levels. |
Investigation and Diagnosis
Concept-Based Investigations (Educational Purposes)
Disclaimer
- This section is intended to outline the different investigations used in prostate cancer and their respective purposes. It is designed for concept-based understanding, as exam questions frequently test which investigation is used for what purpose, rather than strict step-by-step guideline pathways.
- Importantly, NICE guidelines do NOT recommend routine use of all these investigations in every patient. See the section below for details on NICE guideline.
Initial assessment:
- PSA and DRE assess the risk of prostate cancer
- They are NOT diagnostic alone
Diagnostic investigations:
- 1st line: multi-parametric MRI
- Definitive test: prostate biopsy
- Staging: isotope bone scan (to identify bone metastases)
Histological Findings in Prostate Cancer
Key histological features
- Small, crowded glands infiltrating normal prostate tissue
- Loss of basal cell layer (key diagnostic feature)
- Enlarged nuclei with prominent nucleoli
- Irregular gland architecture
- Infiltrative growth pattern (not well circumscribed)
The Gleason score is used to grade prostate cancer:
- The score is derived from 2 numbers: 1) the most common growth pattern, and 2) the second most common growth pattern
- Each growth pattern is graded 1-5
- This gives a total score that is out of 10
In practice, grades 1-2 are not used, so the total score is typically 6 (3+3) – 10 (5+5)
Simplified Gleason score interpretation:
- 6 – low risk
- 7 – intermediate risk
- 8-10 – high risk
NICE Guidelines
Diagnostic approach:
| 1st line investigation | Multiparametric MRI and report the results with a 5-point Likert scale |
| Further investigations | Subsequent action depends on the Likert scale:
|
Some reasons to omit investigations:
- Do not routinely offer multiparametric MRI to patients who are NOT going to be able to have radical treatment
- If the clinical suspicion of prostate cancer is high (↑ PSA and evidence of bone metastases from a positive isotope bone scan or sclerotic metastases on plain radiographs) → do not offer prostate biopsy for histological confirmation
NICE does not recommend offering other imaging techniques routinely:
- CT should only be considered for people with histologically proven prostate cancer for whom MRI is contraindicated
- Isotope bone scan should NOT be routinely offered to those with CPG 1 or 2 localised prostate cancer (due to low risk of bone metastases)
- Offer isotope bone scans when hormonal therapy is being deferred as part of watchful waiting to asymptomatic people who are at high risk of developing bone complications
Risk Stratification – CPG (Cambridge Prognostic Group)
The Cambridge Prognostic Group (CPG) is used to stratify the risk of prostate cancer and guide management. The CPG is based on 3 main factors:
- PSA level (the higher, the worse)
- T stage (tumour size, derived from imaging)
- Gleason score (based on histology)
The Full CPG
| CPG | Criteria |
|---|---|
| 1 |
|
| 2 |
|
| 3 |
OR
|
| 4 | ANY of the following:
|
| 5 |
OR
OR
|
It would be unnecessary to learn the entire CPG grouping.
One may benefit by learning how the Gleason score corresponds to the disease risk / GPG grouping (roughly):
- Gleason 6 – low risk (CPG 1)
- Gleason 7 – intermediate risk (GPG 2-3)
- 3+4 (=7) is better than 4+3 (=7)
- Gleason 8-10 – high risk (CPG 4-5)
Management
Disclaimer: The following is a simplified summary of NICE guideline recommendations.
It would be unnecessary to learn the full NICE guideline, based on the exact CPG groupings. For exam purposes, the key distinctions to understand are: (1) low-risk disease, (2) high-risk disease, and (3) metastatic disease.
Management Approach
Localised Prostate Cancer
Management depends on the CPG group:
| Risk group | CPG group | Recommended 1st line management |
|---|---|---|
| Low risk | 1 | Offer active surveillance |
| Intermediate risk | 2-3 | Offer a choice of:
|
| High risk | 4-5 | Do not offer active surveillance
Offer:
Consider docetaxel chemotherapy in those who are given androgen deprivation therapy and have high-risk disease |
Metastatic Prostate Cancer
Metastatic prostate cancer is managed with systemic therapy of:
- Docetaxel chemotherapy, and
- Androgen deprivation therapy
Details on Management Options
Active Surveillance
Active surveillance involves:
- Avoiding / delaying surgery (prostatectomy) or radiotherapy
- Regular disease monitoring with DRE, PSA testing, and multiparametric MRI +/- biopsy
Radical Prostatectomy
Procedure Information
A radical prostatectomy entails:
- Removal of the following structures
- Prostate gland
- Seminal vesicles and distal portion of vas deferens
- Prostatic urethra
- Pelvic lymph node dissection is indicated
- Bladder neck is detached from the prostate and re-anastomosed to the remaining membranous urethra
Complications
- Sexual dysfunction
- Erectile dysfunction (due to damage to cavernous nerves) – common
- Loss of ejaculation and fertility (as the prostate, seminal vesicles and the vas deferens are removed)
- Urinary complications
- Urinary incontinence (due to external sphincter injury or deficiency) – most common complication
- Bladder neck contracture
- Urethral stricture
- Bowel dysfunction (e.g. faecal incontinence)
Radical prostatectomy vs radical radiotherapy:
- Urinary continence issues (most common) and erectile dysfunction are the major adverse effects associated with radical prostatectomy
- Bowel dysfunction is more prominently linked to radical radiotherapy
Radical Radiotherapy
Choice of Radiotherapy
- External beam radiotherapy – primary treatment option
- Brachytherapy is typically used as an intensification measure (in combination with external beam radiotherapy)
Note that radical radiotherapy should be combined with androgen deprivation therapy
Complications
- Bowel dysfunction
- Faecal incontinence
- Small increased risk of colorectal cancer
- Radiation-induced enteropathy
- Sexual dysfunction
- Erectile dysfunction
- Loss of ejaculation and fertility
- Urinary complications
- Urinary incontinence
Radical prostatectomy vs radical radiotherapy
- Urinary continence issues and erectile dysfunction are the major adverse effects associated with radical prostatectomy
- Bowel dysfunction is more prominently linked to radical radiotherapy
Androgen Deprivation Therapy (Hormone Therapy)
Choice of Androgen Deprivation Therapy
Recommended 1st line androgen deprivation therapy:
| Class | Examples |
|---|---|
| GnRH (LHRH) agonist (chemical castration) |
Initiation of GnRH agonist can cause an initial surge in testosterone, which can cause a tumour flare. BNF: manufacturers advise that the use of prophylactic anti-androgen therapy (e.g. cyproterone acetate) with initial GnRH agonist therapy |
| Surgical castration |
|
2nd line androgen deprivation therapy:
- Bicalutamide monotherapy can be offered to those who wish to retain sexual function but are willing to accept the adverse impact on overall survival and gynaecomastia
- GnRH antagonist (e.g. degarelix, relugolix)
How does GnRH agonist produce an androgen deprivation effect?
- Initial stimulation phase: GnRH agonists strongly activate pituitary GnRH receptors → temporary rise in LH and FSH → short-term increase in testosterone (tumour flare)
- Continuous agonist exposure causes pituitary GnRH receptors to become desensitised
- LH and FSH production collapse and the testes stop producing testosterone
- Within 2–4 weeks, testosterone falls to castrate levels (<0.7 nmol/L)
Adverse Effects of Androgen Deprivation Therapy
Shared adverse effects (all types) → resemble “menopause-like features“:
| Category | Specific features | Management |
|---|---|---|
| Sexual dysfunction |
|
Important to advise patients on the risk of sexual dysfunction before starting treatment
Management:
|
| Vasomotor symptoms |
|
Management of hot flushes:
|
| MSK effects |
|
Androgen deprivation therapy is a major risk factor for osteoporosis:
Offer supervised resistance and aerobic exercise to reduce fatigue and improve quality of life |
Adverse effects specific to each class:
| Class | Adverse effects | Notes |
|---|---|---|
| GnRH agonist (e.g. goserelin) |
|
Offer prophylactic anti-androgen therapy (e.g. cyproterone acetate) with initial GnRH agonist therapy |
| GnRH antagonist (e.g. degarelix, relugolix) |
|
Advantages:
|
| Steroidal anti-androgens (e.g. cyproterone acetate) |
|
Only used short-term for flare prevention and management of hot flush |
| Non-steroidal anti-androgens (e.g. bicalutamide) |
|
Only offer if the patient wishes to retain sexual function but is willing to accept the adverse impact on survival and gynaecomastia
Offer prophylactic radiotherapy to both breasts in patients who are starting long-term bicalutamide monotherapy (>6 months) |