Prostate cancer

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Prostate adenocarcinoma ranges from indolent organ-confined tumours to metastatic androgen-driven and later castration-resistant disease; grade group, stage, PSA, life expectancy, symptoms and treatment preferences determine benefit. Risk rises markedly with age and is higher in Black men, reflecting inherited susceptibility and complex population factors rather than a single causal exposure. A first-degree family history and pathogenic BRCA2, BRCA1, ATM, mismatch-repair or other DNA-repair variants increase risk and can change systemic options. Many adenocarcinomas arise posteriorly in the peripheral zone, allowing clinically silent growth before urethral obstruction develops. Gleason pattern and ISUP grade group reflect gland formation and predict invasion, metastasis and the value of definitive treatment.

Recognition depends on the tempo, host context and anatomical pattern rather than one isolated result. Many localised cancers are detected after informed PSA testing rather than symptoms and require risk estimation rather than automatic treatment. Frequency, poor stream and nocturia are more often benign enlargement, but examination and PSA context determine further assessment. A hard, irregular or fixed prostate increases concern even with a PSA that is not markedly raised. Investigation should answer immediate safety, diagnostic confirmation and extent in that order. PSA with informed discussion Interpret against age, prostate volume, trend, examination, infection, ejaculation and instrumentation; repeat a moderately raised result under appropriate conditions when safe. Multiparametric MRI before biopsy NICE recommends pre-biopsy mpMRI; Likert or PI-RADS suspicion guides targeted sampling, but a negative MRI does not eliminate clinically significant cancer in every risk context. Transperineal targeted and systematic biopsy Combine MRI-targeted cores with systematic strategy according to pathway; transperineal access lowers infectious risk and adequate sampling prevents undergrading.

Management is determined by physiological urgency, disease extent, treatment intent and the person's priorities. The pathway moves through move from psa to mri and biopsy, then match treatment burden to cancer risk, then intensify initial androgen deprivation; each transition requires named multidisciplinary ownership. Follow-up must anticipate metastatic spinal cord compression, skeletal-related events, urinary obstruction while measuring function and treatment toxicity.

Key points

Asymptomatic PSA abnormality is a pivotal clue in Prostate cancer: Many localised cancers are detected after informed PSA testing rather than symptoms and require risk estimation rather than automatic treatment.
Immediate priority in unstable Prostate cancer: Activate the MSCC pathway for spinal symptoms, catheterise and treat infection or renal obstruction when safe, involve urology urgently and do not delay emergency care while obtaining an elective PSA or biopsy.
PSA with informed discussion is used early to estimate cancer probability while explaining false positives, overdiagnosis and consequences of further tests. Interpret against age, prostate volume, trend, examination, infection, ejaculation and instrumentation; repeat a moderately raised result under appropriate conditions when safe.
Multiparametric MRI before biopsy refines the next decision because nICE recommends pre-biopsy mpMRI; Likert or PI-RADS suspicion guides targeted sampling, but a negative MRI does not eliminate clinically significant cancer in every risk context.
Move from PSA to MRI and biopsy: Discuss PSA limitations, exclude or treat infection and repeat a moderately raised result when appropriate, using life expectancy and preferences in referral decisions.
Match treatment burden to cancer risk: Compare radical prostatectomy and external-beam or brachytherapy options using urinary, bowel, sexual, anaesthetic and oncological outcomes.
A major avoidable harm is metastatic spinal cord compression; Vertebral or epidural disease can cause irreversible weakness and sphincter loss unless dexamethasone, MRI and definitive treatment occur urgently.
A common diagnostic trap is benign prostatic enlargement: Common transition-zone enlargement causes urinary symptoms and PSA elevation without the grade and invasion pattern of cancer.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Age and ancestry

Risk rises markedly with age and is higher in Black men, reflecting inherited susceptibility and complex population factors rather than a single causal exposure.

Family and inherited risk

A first-degree family history and pathogenic BRCA2, BRCA1, ATM, mismatch-repair or other DNA-repair variants increase risk and can change systemic options.

Androgen signalling

Normal prostate development and most early cancers depend on androgen-receptor activity, making hormonal deprivation therapeutically effective but not permanently curative in advanced disease.

Sporadic genomic evolution

TMPRSS2–ERG rearrangement, PTEN loss, TP53 alteration and later androgen-receptor amplification create heterogeneous progression and resistance. In Prostate cancer, this distinction materially changes aetiological assessment.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Peripheral-zone origin
Many adenocarcinomas arise posteriorly in the peripheral zone, allowing clinically silent growth before urethral obstruction develops.
2
Grade architecture
Gleason pattern and ISUP grade group reflect gland formation and predict invasion, metastasis and the value of definitive treatment.
3
Lymphatic and skeletal spread
Tumour reaches pelvic nodes and bone, often producing osteoblastic lesions, marrow compromise and skeletal events. In Prostate cancer, this distinction materially changes mechanistic assessment.
4
Androgen dependence
Lowering testosterone suppresses most metastatic disease initially, but resistant clones restore receptor signalling or adopt androgen-independent phenotypes.
5
Local extension
Extracapsular, seminal-vesicle and bladder-base invasion affects margin, radiotherapy field, urinary function and cure probability. In Prostate cancer, this distinction materially changes mechanistic assessment.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Asymptomatic PSA abnormality

Many localised cancers are detected after informed PSA testing rather than symptoms and require risk estimation rather than automatic treatment.

Lower urinary tract symptoms

Frequency, poor stream and nocturia are more often benign enlargement, but examination and PSA context determine further assessment.

Abnormal rectal examination

A hard, irregular or fixed prostate increases concern even with a PSA that is not markedly raised.

Metastatic bone disease

Persistent back, hip or rib pain, fracture, weight loss or anaemia may be the first presentation of advanced cancer.

Neurological deficitRed flag

Weakness, gait change, sensory level or bladder dysfunction with back pain is suspected MSCC and requires emergency imaging.

Obstructive renal injury

Retention, bilateral hydronephrosis or rising creatinine can result from local tumour and needs urological decompression assessment.

Red flags requiring action

New back pain, leg weakness, sensory change or sphincter dysfunction suggests metastatic spinal cord compression.
Acute urinary retention, anuria, hydronephrosis or rising creatinine suggests clinically important outlet or ureteric obstruction.
Bone pain, pathological fracture, weight loss or anaemia suggests metastatic burden.
Visible haematuria or recurrent infection needs independent bladder and urinary-tract assessment rather than attribution to prostate cancer.
A rapidly rising or persistently abnormal PSA remains concerning after infection, instrumentation and benign causes are considered.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
PSA with informed discussionFirst step
Why
Estimate cancer probability while explaining false positives, overdiagnosis and consequences of further tests.
Interpretation and limitations
Interpret against age, prostate volume, trend, examination, infection, ejaculation and instrumentation; repeat a moderately raised result under appropriate conditions when safe.
02
Multiparametric MRI before biopsy
Why
Localise suspicious lesions, estimate stage and reduce unnecessary biopsy in selected men.
Interpretation and limitations
NICE recommends pre-biopsy mpMRI; Likert or PI-RADS suspicion guides targeted sampling, but a negative MRI does not eliminate clinically significant cancer in every risk context.
03
Transperineal targeted and systematic biopsy
Why
Confirm histology, grade group and tumour burden when biopsy is indicated.
Interpretation and limitations
Combine MRI-targeted cores with systematic strategy according to pathway; transperineal access lowers infectious risk and adequate sampling prevents undergrading.
04
Local staging MRI review
Why
Assess extracapsular, seminal-vesicle and adjacent-organ involvement for treatment planning.
Interpretation and limitations
Interpret with biopsy grade, PSA and examination; microscopic extension remains possible despite organ-confined imaging.
05
PSMA PET-CT or conventional metastatic staging
Why
Detect nodal and distant spread in higher-risk disease or biochemical recurrence.
Interpretation and limitations
Use the imaging modality commissioned for the clinical state; PSMA-avid lesions can have benign mimics and may require correlation or tissue.
06
Germline and tumour genomic testing
Why
Identify DNA-repair or mismatch-repair alterations that affect relatives and targeted treatment in advanced disease.
Interpretation and limitations
Offer through current eligibility criteria with genetics counselling where germline implications exist; tumour-only findings are not automatically inherited.
07
Baseline hormonal and bone assessment
Why
Prepare for long-term androgen-deprivation toxicity and interpret later castration resistance.
Interpretation and limitations
Record testosterone, cardiovascular and metabolic risk and fracture assessment before or soon after ADT; confirm castrate testosterone when progression occurs.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Benign prostatic enlargement

Common transition-zone enlargement causes urinary symptoms and PSA elevation without the grade and invasion pattern of cancer.

Prostatitis or urinary infection

Inflammation can raise PSA markedly and cause pain or fever; treat infection and reassess rather than biopsy during uncontrolled sepsis.

Bladder cancer

Visible haematuria, irritative symptoms and obstruction may arise from urothelial cancer and require cystoscopic assessment. In Prostate cancer, this distinction materially changes diagnostic assessment.

Other bone disease

Degenerative change, myeloma and other metastases can cause pain or sclerotic lesions; atypical imaging warrants correlation or biopsy.

Small-cell neuroendocrine carcinoma

Rapid visceral progression with relatively low PSA suggests an aggressive variant needing tissue and platinum-based rather than ordinary androgen-only management.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01SuspectMove from PSA to MRI and biopsyFirst stepPSA, examination, symptoms or incidental imaging creates a clinically meaningful possibility of prostate cancer.

1Discuss PSA limitations, exclude or treat infection and repeat a moderately raised result when appropriate, using life expectancy and preferences in referral decisions.
2Obtain pre-biopsy multiparametric MRI and review PSA density, lesion score, examination and family or inherited risk.
3Use targeted plus protocolled systematic transperineal biopsy when risk remains sufficient, reporting ISUP grade, core burden and histological variants.

02LocalisedMatch treatment burden to cancer riskStaging shows non-metastatic disease and curative or surveillance options are available.

1Offer active surveillance for suitable low-risk and selected intermediate-risk disease with a defined PSA, MRI and re-biopsy schedule.
2Compare radical prostatectomy and external-beam or brachytherapy options using urinary, bowel, sexual, anaesthetic and oncological outcomes.
3For higher-risk localised disease, combine radiotherapy with the indicated ADT duration or use surgery within a planned multimodal pathway.

03Metastatic sensitiveIntensify initial androgen deprivationMetastatic prostate adenocarcinoma remains hormone sensitive or presents de novo.

1Start ADT promptly, using an antagonist when avoiding flare is important or cover an agonist flare according to the clinical situation.
2Add an androgen-receptor-pathway agent, docetaxel or triplet treatment for eligible patients according to volume, timing, fitness and current NHS access.
3Address bone pain, MSCC risk, urinary obstruction, genetics, cardiovascular prevention and supportive care at the same visit.

04ResistantConfirm and sequence castration-resistant diseasePSA, radiology or symptoms progress while the patient is receiving ADT.

1Confirm castrate testosterone, adherence and genuine progression, then restage distribution and tempo including visceral or discordant disease.
2Continue ADT and select taxane, androgen-axis, radioligand, PARP-targeted or other treatment by prior exposure, genomics, symptoms and access.
3Biopsy rapidly progressive low-PSA or visceral disease when neuroendocrine transformation would change treatment.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

Produces rapid androgen deprivation without the initial testosterone flare of a GnRH agonist, useful when flare could worsen obstruction or symptomatic metastasis.

Degarelix

Give 240 mg by subcutaneous injection as two 120 mg injections for the loading dose, then 80 mg subcutaneously every month with the first maintenance dose one month later.

Monitor injection reactions, hot flushes, QT risk, liver function, glucose, cardiovascular and bone health; maintain the planned monthly interval and check testosterone if response is uncertain.

Inhibits androgen synthesis and improves outcomes in eligible advanced prostate cancer while background ADT continues.

Abiraterone with corticosteroid

Give abiraterone 1,000 mg orally once daily on an empty stomach. In metastatic hormone-sensitive disease use prednisolone 5 mg once daily; in metastatic castration-resistant disease the licensed regimen uses prednisolone 10 mg daily.

Monitor blood pressure, potassium, fluid retention and liver tests frequently early in treatment; review heart failure, mineralocorticoid toxicity, interactions and corticosteroid sick-day or withdrawal risk.

Provides treatment intensification in fit patients with metastatic hormone-sensitive cancer and remains an option in castration-resistant disease.

Docetaxel

A common metastatic prostate-cancer regimen is 75 mg/m² intravenously every 3 weeks for 6 cycles in hormone-sensitive disease, with corticosteroid and supportive treatment according to the NHS protocol.

Check count, liver function, infection, neuropathy, oedema and performance before each cycle; explain neutropenic-sepsis action and use dose modification rather than treating through major toxicity.

Blocks transient androgen-receptor stimulation until the agonist lowers testosterone.

Bicalutamide for agonist flare protection

When starting a GnRH agonist in a patient at risk of tumour flare, a common regimen is bicalutamide 50 mg orally once daily begun before the first injection and continued for the protocol-defined short period.

This is not required with a GnRH antagonist; review liver function, interactions and whether severe cord or urinary risk instead requires an immediate non-flare strategy.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Metastatic spinal cord compression

Vertebral or epidural disease can cause irreversible weakness and sphincter loss unless dexamethasone, MRI and definitive treatment occur urgently.

Skeletal-related events

Bone metastases cause pain, fracture, marrow suppression and hypercalcaemia, though prostate lesions are often osteoblastic. In Prostate cancer, this distinction materially changes complication assessment.

Urinary obstruction

Local progression can cause retention, infection, haematuria, hydronephrosis and renal failure requiring catheter, stent or nephrostomy.

ADT metabolic and bone harm

Hypogonadism promotes hot flushes, sexual dysfunction, sarcopenia, osteoporosis, diabetes and cardiovascular risk. In Prostate cancer, this distinction materially changes complication assessment.

Castration resistance

Progression despite castrate testosterone requires confirmation, restaging and a new systemic sequence rather than simply stopping ADT.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

During active surveillance, use the agreed PSA kinetics, examination, repeat MRI and biopsy triggers rather than PSA alone.
After radical treatment, trend PSA using modality-specific expectations and investigate biochemical recurrence before symptoms arise.
On ADT, monitor testosterone when clinically needed, PSA, symptoms, blood pressure, weight, glucose or HbA1c, lipids and cardiovascular risk.
Perform baseline and interval fracture-risk assessment, encourage resistance exercise and ensure calcium and vitamin D sufficiency without automatic excess supplementation.
With advanced disease, review pain, neurological or urinary red flags, blood count, renal, liver and alkaline phosphatase trends and imaging response.
Track genomic results and family implications to completion before later-line targeted-treatment decisions are required.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

MRI comes before first biopsy

Pre-biopsy mpMRI localises significant disease, informs targeted transperineal sampling and can reduce unnecessary biopsy in selected men.

Symptoms are often benign

Lower urinary tract symptoms commonly arise from benign enlargement; cancer risk follows PSA, examination, MRI and tissue rather than symptoms alone.

A negative MRI is not zero risk

PSA density, examination, family history and clinical concern can still justify biopsy despite no target lesion.

ADT should usually continue

Castration-resistant progression means tumour growth despite low testosterone, not that androgen deprivation has become irrelevant.

Low PSA can be aggressive

Rapid visceral progression with little PSA rise raises neuroendocrine transformation and should prompt fresh tissue when feasible.

11Common pitfallsFrequent interpretation and management errors.

01
Biopsying before pre-biopsy mpMRI without a pathway-specific reason.
02
Treating an infected or recently instrumented PSA as a cancer diagnosis.
03
Starting a GnRH agonist without considering dangerous tumour flare.
04
Calling PSA progression castration resistant without checking testosterone and adherence.
05
Ignoring metabolic, cardiovascular and fracture prevention during ADT.
06
Attributing visible haematuria to prostate cancer without assessing bladder disease.