Prostate cancer

• Prostate cancer is a slow-growing cancer of the prostate gland, and it is the second most commonly diagnosed cancer in men worldwide, with about 1.46 million new diagnoses and about 396,792 deaths in 2022. ^[1]
• Most early prostate cancers cause no symptoms at all. They are found because of a raised PSA or an abnormal digital rectal examination, and they grow so slowly that many men would never have known about them in their lifetime.
• The diagnosis is built in stages: a raised PSA or an abnormal examination leads to prostate MRI, and when needed a targeted biopsy. The biopsy then gives the grade (Gleason/ISUP grade group) that drives every later decision.
• Once the grade and stage are known, the cancer is placed in a risk group. Low-risk disease is usually watched (active surveillance), while higher-risk disease is treated with surgery or radiotherapy, often combined with androgen deprivation therapy (ADT).
• Advanced disease is kept under control with ADT plus other drugs. This page also covers PSA recurrence after treatment, spinal cord compression as an emergency, and how to proceed when tests or drugs are not available.

By the end of this page you should be able to:

1. Explain the main risk factors for prostate cancer, including age, family history, inherited mutations such as BRCA2, and the higher incidence and mortality in men of African ancestry.
2. Recognise how prostate cancer presents, from an incidental PSA rise to locally advanced disease and bone or spinal metastases.
3. Interpret screening recommendations, including the shared decision-making approach of the USPSTF and the individual early-detection position of the EAU.
4. Work through the diagnostic pathway of PSA, MRI, targeted biopsy and Gleason/ISUP grading.
5. Apply the EAU risk groups and match them to active surveillance, radical prostatectomy, radiotherapy with ADT, and treatment of metastatic disease.
6. Describe ADT with GnRH agonists and antagonists, including the flare phenomenon, and state the key doses and monitoring for abiraterone, enzalutamide, docetaxel, radium-223, olaparib and denosumab.
7. Manage PSA recurrence and suspected spinal cord compression, including low-resource considerations.

The prostate is an androgen-dependent gland. Testosterone is converted in the prostate to dihydrotestosterone, which drives both normal growth and cancer growth, and this is why lowering androgen levels is such an effective treatment. Pathology and grade matter as much as anatomy: the same TNM stage can demand different treatment depending on the grade group reported on the biopsy cores. Always think of prostate cancer as a graded disease, not a single entity.

Prostate cancer is a major health problem for men worldwide. In 2022 there were an estimated 1.46 million new diagnoses and 396,792 deaths, making it the second most commonly diagnosed cancer in men and a leading cause of cancer death in men in about a quarter of all countries. ^[1] In Europe it is the most frequently diagnosed cancer in men. Incidence is highest in Australia and New Zealand and in North America (age-standardised rates about 111.6 and 97.2 per 100,000), and in Western and Northern Europe (about 94.9 and 85 per 100,000). It is much lower in Eastern and South-Central Asia (about 10.5 and 4.5 per 100,000), although rates there are rising. ^{[1] [7]}

Mortality is less variable. It is generally highest in populations of African descent (for example, age-standardised rates of about 29 per 100,000 in the Caribbean and 14 to 19 in Sub-Saharan Africa), intermediate in the USA, and very low in Asia (about 2.9 in South-Central Asia). Mortality has fallen in most Western nations, partly because more tumours are now found early, although the size of the fall varies between countries. ^[1]

Age is the most consistent risk factor. Autopsy studies show small, often silent cancers in about 5% of men under 30 years and in up to 59% of men over 79 years, with large differences between populations (for example, 83% in white US men versus 41% in Japan at ages 71 to 80). ^[1] The practical lesson is that many men harbour a prostate cancer that will never affect them in their lifetime. Finding it and treating it aggressively is where much of the harm of PSA screening comes from. ^[7]

Risk factor is any characteristic that makes the cancer more likely to occur. For prostate cancer the main ones are fixed, but they matter for deciding who to test and how aggressively to treat.

Age is the strongest risk factor. Men of African ancestry living in Western countries have more unfavourable outcomes, are more likely to be diagnosed with advanced disease and are more likely to be upgraded after prostatectomy than white men, although overall survival and prostate cancer specific mortality do not clearly differ between white, black and Hispanic men with metastatic disease in population data. African ancestry as a category is based on a mix of ancestry, skin colour and geography; within it there are many different regions of origin. Black men without prostate cancer also appear to have higher baseline PSA levels, which can increase detection and partly explain the observed differences. Racial disparities in access to screening and treatment may also exist, and few major trials report race, education or socioeconomic status in detail. ^[1]

A small sub-population has true hereditary prostate cancer, defined as at least three cases in one family, prostate cancer in three successive generations, or at least two cases in one family diagnosed before age 55. In a Swedish population-based study, the probability of high-risk prostate cancer at age 65 was 11.4% (against a population risk of 1.4%) and of any prostate cancer 43.9% (against 4.8%) when a man's father and two brothers were affected. In a large US database, hereditary prostate cancer was reported by 2.18% of participants and carried a relative risk of 2.30 for any prostate cancer, 3.93 for early-onset disease, 2.21 for lethal disease and 2.32 for clinically significant disease. Familial prostate cancer means at least two first- or second-degree relatives on the same side of the family. The EAU divides both groups as follows. ^[1]

Pathogenic germline mutations in BRCA2, HOXB13, CHEK2, BRCA1, ATM, NBS1 and the mismatch repair genes that cause Lynch syndrome have each been linked to an increased risk of prostate cancer. Germline mutations leading to prostate cancer are rare (about 1 in 300), but their impact on risk is strong and they are much more common in advanced disease. BRCA2 carries a relative risk of 2.5 to 4.6 overall and 8 to 23 for disease before age 55; it is found in about 5.3% of men with metastatic disease and is an independent predictor of metastasis and worse prostate cancer specific survival. Germline mutation testing is considered important for identifying families at high risk and, in metastatic disease, for selecting targeted treatment. In the IMPACT screening study, BRCA2 carriers had a higher incidence of cancer, younger age at diagnosis and more clinically significant tumours than non-carriers. BRCA1 carriers showed no clear difference. ^[1]

The association between metabolic syndrome and prostate cancer overall is weak, but somewhat stronger for aggressive disease. The components with the strongest significant links are hypertension (p = 0.035) and a waist circumference of at least 102 cm (p = 0.007). Diabetes appears not to increase risk and may reduce it; metformin does not reliably prevent prostate cancer. Obesity is associated with lower risk of low-grade disease (odds ratio 0.79) but higher risk of high-grade disease (odds ratio 1.28). Cholesterol levels are not associated with risk, although statin use may slightly reduce it. Blood pressure medication with renin-angiotensin inhibitors may slightly reduce risk, while calcium channel blockers may slightly increase it. ^[1]

Among exogenous factors, 5-alpha-reductase inhibitors reduce the risk of low-grade (ISUP grade group 1) prostate cancer by about 25% but carry a small increased risk of high-grade disease, and none is approved for chemoprevention in Europe. Testosterone supplementation does not appear to increase risk in hypogonadal men, and very low free testosterone is associated with a below-average risk. Smoking increases prostate cancer death (relative risk 1.24) and is linked to aggressive disease even after quitting. Diets containing tomatoes (especially cooked), cruciferous vegetables, soy, coffee and fish have variably been associated with reduced risk or aggressiveness, while high red or processed meat intake may increase it, but no causal relationship is proven and no specific prevention can be recommended. ^[1]

Inflammatory bowel disease, particularly ulcerative colitis, has been associated with a higher rate of clinically significant (ISUP grade group 2 or higher) disease. Infections such as gonorrhoea, and possibly HPV type 16, are linked to higher incidence. Height, vertex pattern baldness, night-shift work, certain occupations and cadmium exposure have all been reported as associations. Aspirin, NSAIDs, ultraviolet radiation exposure, circumcision and higher ejaculation frequency have been associated with slightly reduced risk. A Mendelian randomisation study linked twelve gut microbial taxa to risk, but this is not yet clinically useful. Well-established disproven factors include vasectomy and self-reported acne. ^[1]

Prostate cancer begins as androgen-dependent epithelial proliferation. The prostate concentrates dihydrotestosterone, which activates the androgen receptor and drives both normal and malignant growth. Over time, clones with less dependence on androgen signalling appear; this drift toward androgen independence underlies the eventual failure of hormone therapy and the transition to castration-resistant disease. Locally advanced tumours invade the capsule, seminal vesicles and surrounding structures, then spread through lymphatics to pelvic nodes and through the blood, preferentially to bone. Bone metastases in prostate cancer are usually osteoblastic: new, brittle bone is deposited, which explains why affected men can have both a rising alkaline phosphatase and a high risk of fracture or spinal compression even while the underlying disease is relatively indolent.

Localised prostate cancer is asymptomatic in most men. It is found either by PSA testing or during investigation of bladder symptoms. Symptoms appear when the tumour grows or spreads. Local progression can cause lower urinary tract symptoms (poor stream, hesitancy, nocturia, urgency, retention), haematuria, haematospermia, erectile dysfunction, pelvic or perineal pain. On examination the prostate may feel hard, nodular or irregular on digital rectal examination, and the EAU notes that a suspect digital rectal examination in a man with PSA of 4 ng/mL or less has a positive predictive value for prostate cancer of 5 to 30 per cent, and that digital rectal examination is an independent predictor of advanced disease (odds ratios 11.12 for cT3 and 5.28 for cT4). Abnormal digital rectal examination is also associated with a higher ISUP grade group and predicts clinically significant disease during active surveillance. ^[2]

Metastatic disease declares itself through bone pain (often in the spine, pelvis, ribs or femur), pathological fracture, spinal cord compression (back pain with weakness, sensory change or sphincter disturbance), anaemia, weight loss, fatigue and, rarely today, paraplegia. Very high PSA values, together with bone pain, support metastatic disease, and when the clinical picture is unmistakable the biopsy can even be omitted if comorbidity would preclude further treatment in any case. Paraneoplastic features are uncommon. Progressive, rapidly rising PSA without symptoms is the commonest modern relapse pattern after treatment. ^[2]

A raised PSA is not cancer. Benign prostatic hyperplasia, prostatitis and urinary tract infection all raise it, and PSA is organ-specific, not cancer-specific. A hard prostate on examination can also be seen with chronic infection and stones. On the other hand, prostate cancer can be missed if the PSA is normal, since some men have cancer despite low values. In younger men with a raised PSA, always consider infection and inflammation first. In the secondary care setting the main alternative diagnoses for a prostate mass are benign prostatic hyperplasia, granulomatous prostatitis and urothelial tumour of the prostatic urethra or bladder.

The pathway now used in most guidelines is MRI first, then targeted biopsy only when needed. ^[2]

PSA is a glycoprotein produced by prostate epithelial cells. It is prostate-specific but not cancer-specific. There is no agreed abnormal threshold; it behaves as a continuous number, and higher values mean higher likelihood of cancer. A PSA of 3 ng per mL or less is often used as a screening trigger, and PSA at or above 4 ng per mL has an estimated sensitivity of 0.93 and specificity of 0.20 for cancer in referred men. Because PSA production is androgen-dependent, 5-alpha-reductase inhibitors (finasteride, dutasteride) reduce PSA by about 50%, so values must be doubled or prostate volume considered instead; PSA density is less affected. In men with a moderately raised PSA (3 to 10 ng per mL), a repeat test after about 4 weeks is sensible, because one third of men show a difference of more than plus or minus 1 ng per mL on retesting and about a fifth fall below 3 ng per mL. PSA density (PSA divided by prostate volume) is a strong predictor of clinically significant cancer: below 0.09 ng per mL per mL, only about 4% of men have clinically significant disease, while values above 0.1 to 0.15 predict cancer. PSA must be measured under standardised conditions (no ejaculation, no rectal examination immediately beforehand, no infection, no retention) and after a biopsy has settled (at least one month delay). ^{[2] [6][7] [11]}

Digital rectal examination assesses size, symmetry and consistency and is the basis of clinical T staging. About 18% of cancers are detected by a suspicious examination alone, whatever the PSA. An abnormal examination with an elevated PSA more than doubles the chance of a positive biopsy. Clinical stage is based on digital rectal examination, with imaging reported separately. ^[2]

Multiparametric MRI, now usually biparametric in expert centres, is the central imaging test. It has pooled sensitivity of 0.91 for ISUP grade group 2 or higher cancers (0.95 for grade group 3 or higher) when template biopsy is the reference. The PI-RADS version 2.1 score stratifies risk of clinically significant cancer: about 6% for PI-RADS 1 to 2, 20% for PI-RADS 3, 55% for PI-RADS 4 and 83% for PI-RADS 5. PSA density allows further stratification of PI-RADS 3 lesions. MRI is also used for staging (extracapsular extension, seminal vesicle invasion) and for selecting a biopsy target. Biparametric MRI (without contrast) has been shown to be non-inferior to multiparametric MRI in prospective studies. Image quality, reader experience and centre volume all affect these numbers; inter-reader reproducibility is at best moderate. ^{[2] [3]}

Prostate-specific membrane antigen (PSMA) positron emission tomography combined with CT (PSMA PET/CT) is mainly used for staging, but it can also guide targeted biopsy. Hybrid PSMA PET/CT imaging has pooled sensitivity of 0.89 and specificity of 0.56 for clinically significant cancer. Adding PSMA PET to MRI improves sensitivity (97 versus 83 per cent) and negative predictive value (91 versus 72 per cent), at the cost of lower specificity. The PRIMARY score for intraprostatic PSMA activity showed sensitivity 88%, specificity 64%, positive predictive value 76% and negative predictive value 81% for clinically significant cancer, compared with 83%, 53%, 69% and 72% for a PI-RADS score of 3 to 5 versus 2 or less. PSMA PET is also central to the staging of men with high-risk disease and to the follow-up of suspected recurrence. ^[2]

As a rule, the ideal systematic sequence in this library is: first exclude benign causes of a raised PSA, repeat if appropriate, scan the prostate with MRI, biopsy the target (usually transperineally, ideally with perilesional cores), then stage. A biopsy may be omitted when it cannot change management: a frail man with a very high PSA and metastases already visible on bone scan may not need histology if comorbidities preclude intensifying treatment beyond ADT.

Pre-biopsy MRI is the current standard; biopsy is MRI-targeted plus, usually, systematic sampling. Core biopsy is preferred over fine needle aspiration. The transperineal route is increasingly preferred to reduce sepsis. A repeat PSA in men with an initial 3 to 10 ng per mL value, as above, reduced the number of biopsies at the cost of missing a small proportion of grade group 2 or higher cancers in the Stockholm3 trial. In men with a negative biopsy and an MRI Likert score of 3 or more, multidisciplinary review and repeat biopsy should be considered. In men with low suspicion (PSA density below 0.15 ng per mL per mL and slow or no PSA rise) discharge to primary care with regular PSA is appropriate. ^[6]

Prostate cancer is staged with the UICC/AJCC TNM classification, 8th edition. Clinical T stage is based on digital rectal examination only; any imaging findings are reported separately. Nodal status is regional pelvic nodes; metastases are M1a non-regional nodes, M1b bone and M1c other sites. Pathological stage is the surgical specimen and largely parallels clinical stage. ^[3]

Grade is reported with the ISUP 2014 grade group system, which has five groups: grade group 1 (Gleason sum 6), grade group 2 (Gleason 3+4=7), grade group 3 (Gleason 4+3=7), grade group 4 (Gleason sum 8) and grade group 5 (Gleason sum 9 to 10). The 2005 and 2014 ISUP revisions have shifted grading upward over time, so older series are not directly comparable. Grade group 1 disease on its own behaves like a benign condition: at radical prostatectomy, extraprostatic extension is rare, biochemical recurrence is low, and metastases and seminal vesicle invasion do not occur; it can therefore be called clinically insignificant. However, biopsy grade group 1 can under-sample a higher grade, especially with high PSA density or a visible MRI lesion, and grade group 1 can progress to a higher grade at about 1% per year. ^[3]

The EAU risk classification, based on the D'Amico system, combines clinical T stage, PSA and ISUP grade group to predict the risk of biochemical recurrence after radical prostatectomy or radiotherapy. Intermediate risk is split into favourable and unfavourable, which improves prediction of prostate cancer specific mortality. The Cambridge Prognostic Groups five-tier model is more discriminative, and NICE uses it for treatment assignment. ^[3][6]

NICE's risk stratification uses the Cambridge Prognostic Groups, which were originally validated with different thresholds: group 1 is Gleason 6 with PSA less than 10 micrograms per L and T1 to T2; group 5 includes any two of Gleason 8 or higher, PSA greater than 20 micrograms per L or T3, or Gleason 9 to 10, or T4. NICE also does not routinely offer isotope bone scans for CPG 1 or 2 disease, and offers them in watchful waiting when hormonal therapy is being deferred and there is high risk of bone complications. ^[6]

For localised disease, no extra staging is usually needed for low-risk tumours. For higher-risk tumours, staging includes cross-sectional imaging (CT or MRI of the abdomen and pelvis) to assess the nodes and distant sites, and a bone scan if bone metastases are suspected. Multiparametric MRI for local staging is offered before treatment according to NICE. For men with CPG 4 or 5, the possibility of pelvic nodal involvement can be estimated with the Roach formula: percentage nodal risk = two-thirds PSA + (10 x [Gleason score - 6]). NICE recommends pelvic radiotherapy for locally advanced disease when this risk exceeds 15 per cent. PSMA PET/CT is increasingly used for higher-risk staging and for biochemical recurrence, partly because it detects disease earlier than conventional imaging. ^[6]

Two different conservative strategies exist. Watchful waiting is palliative in intent, for men with a life expectancy of less than 10 years in whom curative treatment is not indicated; tumours are then monitored for symptom progression and hormonal treatment is started when needed. Active surveillance is curative in intent, for men with low-risk and some intermediate-risk disease who have a life expectancy of more than 10 years; the tumour is monitored intensively so that it can be treated before it becomes dangerous. More than one third of men on active surveillance are reclassified during follow-up. ^[4]

EAU recommendations make active surveillance the first management option for men with EAU low-risk prostate cancer who have adequate life expectancy. Common selection criteria are ISUP grade group 1 (on systematic biopsy), clinical stage cT1c or cT2a, PSA less than 10 ng per mL and PSA density less than 0.15 ng per mL per mL; some centres now accept carefully selected ISUP grade group 2 low-volume disease (less than 10% pattern 4, PSA less than 10 ng per mL, low core positivity). Features such as cribriform histology, predominant ductal carcinoma, sarcomatoid or small-cell carcinoma, extraprostatic extension or perineural invasion on biopsy are reasons not to offer surveillance. Men whose cancer is diagnosed on targeted biopsy alone should have a re-biopsy within six to twelve months (a confirmatory biopsy) unless systematic and targeted biopsy were combined. The Movember consensus group identified ISUP grade group and MRI as the most important eligibility factors. Active reclassification happens in more than a third of men during follow-up, mostly due to upgrading or an increase in tumour volume. ^[4]

Programmes differ, but EAU-style surveillance includes digital rectal examination at least yearly, PSA at least every six months, repeat MRI and repeat biopsy, with individualised schedules as risk increases. Stable MRI (PRECISE 3), together with a low PSA density (less than 0.15), identifies men in whom a repeat biopsy may be omitted. A single negative (that is, no-cancer) repeat biopsy during surveillance halves the risk of future reclassification. NICE recommends a PSA every 3 to 4 months in the first year, MRI at 12 to 18 months, then PSA every 6 months with yearly digital rectal examination and MRI as required, with reassessment with MRI or biopsy if PSA changes are concerning. Men should be allowed to move from surveillance to radical treatment at any time on request. ^[4][6]

For EAU low-risk disease, active surveillance is preferred. Under NICE guidance, CPG 1 tumours are offered active surveillance, and radical prostatectomy or radical radiotherapy is only considered if surveillance is not suitable or acceptable. NICE CPG 2 tumours are offered a choice of active surveillance, radical prostatectomy or radical radiotherapy. NICE CPG 3 tumours are offered radical prostatectomy or radical radiotherapy, with active surveillance as an option for men who do not want immediate treatment. ^[6]

Radical treatment consists of radical prostatectomy (usually laparoscopic or robot-assisted) or radical external beam radiotherapy. NICE recommends hypofractionated image-guided IMRT at 60 Gy in 20 fractions if not contraindicated, otherwise 74 Gy in 37 fractions. Brachytherapy may be added to external beam radiotherapy for CPG 2 to 5 disease but is not used alone for CPG 4 or 5 disease. ^[6]

For NICE CPG 2 to 5 localised or locally advanced disease, radical radiotherapy is combined with 6 months of ADT; for CPG 4 and 5, continuing ADT for up to 3 years can be discussed. NICE also offers pelvic radiotherapy when the Roach-estimated pelvic nodal risk exceeds 15 per cent. Docetaxel chemotherapy at 75 mg per m2 intravenously every 3 weeks for six cycles (with or without daily prednisolone), started within 12 weeks of beginning long-term ADT, is discussed for high-risk non-metastatic disease (T3 or T4, Gleason 8 to 10, or PSA greater than 40 micrograms per litre) in men with no significant comorbidities and adequate life expectancy, because it delays progression (median time to progression about 5 years versus 6 years in the cited UK trial), although the survival benefit is not established. ^{[6] [11]}

Immediate postoperative radiotherapy after prostatectomy is not offered outside a clinical trial, and adjuvant hormonal therapy after prostatectomy is not offered outside a trial. ^[6]

Before radical treatment, men must be counselled about sexual function, fertility (sperm storage should be offered), urinary continence, and potential radiation-induced bowel injury. PDE5 inhibitors, vacuum devices or (for intractable incontinence) an artificial urinary sphincter are standard follow-up measures. Unproven focal treatments (high-intensity focused ultrasound, cryotherapy) are not offered outside trials. ^[6]

ADT means lowering circulating testosterone to castrate levels (less than 50 ng per dL). It can be achieved by bilateral orchidectomy or, more commonly, by drugs.

• GnRH (LHRH) agonists: leuprolide, goserelin, triptorelin. These suppress pituitary gonadotrophin release. Leuprolide is given as a depot injection at intervals of about 1, 3, 4 or 6 months depending on the formulation (check the product label for the dose). ^[11]
• GnRH antagonists: degarelix or the oral agent relugolix. They block the receptor directly.
• Antiandrogens such as bicalutamide: 150 mg as monotherapy is the off-label dose that preserves sexual function in selected men, with shorter survival than castration; androgen receptor inhibitors (apalutamide, darolutamide) are additional modern agents. ^[6]

A combined androgen blockade (ADT plus an antiandrogen) is not recommended first line in metastatic disease. ^[6]

NICE recommends medroxyprogesterone 20 mg daily for 10 weeks for troublesome hot flushes on long-term ADT, with cyproterone acetate 50 mg twice daily for 4 weeks if that fails, and prophylactic breast bud radiotherapy (a single 8 Gy fraction) within the first month for men starting long-term bicalutamide monotherapy, with weekly tamoxifen if gynaecomastia develops. Men on long-term ADT should receive supervised resistance and aerobic exercise at least twice weekly for 12 weeks to reduce fatigue, plus a urological or psychosexual assessment. Intermittent ADT may be considered outside the adjuvant setting, restarting when PSA is 10 ng per mL or above or on symptomatic progression. ^[6]

The backbone of treatment is continuous ADT. Modern standard practice adds either docetaxel (six 3-weekly cycles at 75 mg per m2, started within 12 weeks of beginning ADT) or an androgen receptor pathway inhibitor. NICE recommends offering docetaxel on this schedule to men with newly diagnosed metastatic disease and no significant comorbidities. ^[6] ADT itself, by GnRH agonist or antagonist or bilateral orchidectomy, remains the foundational therapy; orchidectomy remains an alternative for men who prefer it or cannot obtain or tolerate drugs. ^[6] Antiandrogen monotherapy with bicalutamide 150 mg is an option for men who wish to preserve sexual function, accepting reduced overall survival. ^[6] Docetaxel should be avoided or delayed if performance status is poor; men on continuous ADT require careful metabolic, cardiovascular and bone monitoring.

Once the disease progresses despite castrate testosterone (castration-resistant prostate cancer), further lines of systemic therapy are offered according to prior treatment, symptoms, burden of disease and comorbidity.

• Enzalutamide, an androgen receptor inhibitor, 160 mg orally once daily. ^[10]
• Abiraterone, a CYP17 inhibitor, 1000 mg orally once daily taken on an empty stomach, together with prednisone or prednisolone 5 mg twice daily. ^[8]
• Docetaxel 75 mg per m2 intravenously every 3 weeks is recommended within its licensed indications for men with performance-status 60% or greater, stopped at up to 10 cycles, for severe toxicity or progression. ^[6]
• Radium-223, an alpha-emitting radiopharmaceutical concentrated in bone, at 55 kBq per kg intravenously every 4 weeks for six administrations; it is appropriate for men with symptomatic bone-predominant disease and no visceral metastases, and it prolonged survival in the registration trials. ^[10]
• Olaparib 300 mg orally twice daily (total 600 mg per day) for men with mCRPC and pathogenic alterations in homologous recombination repair genes (including BRCA1 or BRCA2) after progression on a new hormonal agent; it is given continuously, with dose reductions (to 250 mg twice daily, then 200 mg twice daily) for toxicity, and it carries a risk of myelodysplastic syndrome and acute myeloid leukaemia of about 1.2%. ^[8]
• In men with BRCA-mutated mCRPC, olaparib is also combined with abiraterone and prednisone.

A GnRH analogue should be continued alongside modern agents in castration-sensitive and castration-resistant disease. Treatment should be stopped or changed in the presence of radiographic or clinical progression. Because nearly half of patients who develop radiographic progression in some trials show no concomitant PSA rise, imaging rather than PSA alone should be used to judge progression. ^[5]

ADT reduces bone mineral density and increases fracture risk, particularly when combined with androgen receptor inhibitors or docetaxel. All men starting long-term ADT should have baseline DEXA assessment of bone density, with repetition at least every two years if bone agents are not used. Vitamin D and calcium levels should be checked and supplemented as required. Bone-protective agents are used when osteoporosis is present, or in men with bone metastases, where they delay skeletal-related events (pathological fracture, spinal cord compression, need for radiotherapy or surgery). ^[5][6]

• Denosumab 120 mg subcutaneously every 4 weeks for bone metastases from solid tumours, including prostate cancer, as an alternative to zoledronic acid. ^[9]
• Bisphosphonates (such as zoledronic acid) are offered to men who are having ADT and have osteoporosis; NICE does not routinely recommend them for primary prevention. ^[6]
• A lower, 6-monthly dose of denosumab (the osteoporosis preparation) is the alternative when bisphosphonates are contraindicated or not tolerated. ^[6]

Good oral hygiene is required before intravenous bisphosphonates to reduce osteonecrosis of the jaw risk, and renal function should be checked before dosing.

After surgery, PSA should be undetectable; after radiotherapy it falls slowly, and the Phoenix definition of radiotherapy failure is a rise of 2 ng per mL above the post-treatment nadir. Biochemical recurrence after prostatectomy is defined as a rising PSA, and a level above 0.4 ng per mL is the threshold that best predicts metastasis. ^[5] Most failures occur within seven years of treatment, so PSA should be checked at least every 6 months for the first 2 years and then at least annually. ^[6] Ultrasensitive assays are controversial. A steadily rising PSA does not always need immediate treatment; salvage radiotherapy to the prostatic bed is offered to men with biochemical recurrence after prostatectomy, with no known metastases and a rising PSA. Hormonal therapy for biochemical relapse is reserved for symptomatic local progression, proven metastases, or a PSA doubling time of less than 3 months. ^[6]

Imaging has no place in routine follow-up while PSA is stable and the patient is asymptomatic; it is reserved for biochemical recurrence, new symptoms or an abnormal examination. All local treatments leave their own side effects, which is why patient-reported outcomes should be recorded. ^[5]

Bone metastases from prostate cancer often involve the spine. A new or worsening back pain in a man with metastatic prostate cancer is a red flag until proven otherwise. Early warning signs are progressive back pain (often worse at night or on lying flat), radicular pain, leg weakness, numbness, altered gait, sensory level, or bladder, bowel or sphincter disturbance. The leuprolide label specifically warns that tumour flare can precipitate spinal cord compression. ^[11]

Suspected cord compression requires same-day management: high-dose corticosteroid, urgent whole-spine MRI, input from oncology, neurosurgery and radiotherapy, and definitive treatment with radiotherapy or surgical decompression-stabilisation depending on the site, number of levels, overall outlook and whether the diagnosis is unclear. Men on GnRH agonists with impending cord compression are better switched to an antagonist (or orchidectomy) to avoid further flare, and they need education about the red flags so that they can seek help early. ^[5][11]

• Local complications: urinary obstruction and retention; haematuria; erectile dysfunction.
• Metastatic complications: bone pain, pathological fracture, spinal cord compression, pancytopenia from marrow replacement, hypercalcaemia.
• Treatment complications: post-prostatectomy incontinence and erectile dysfunction (roughly 13% moderate or severe incontinence at 6 years in the ProtecT data); radiotherapy-related bowel and rectal symptoms; ADT-related hot flushes, gynaecomastia, anaemia, metabolic syndrome, diabetes, cardiovascular events, cognitive change, fatigue and osteoporosis; docetaxel toxicity including febrile neutropenia (about 15 of every 100 treated men) and, rarely, treatment-related death (about 1 of every 100); taxane peripheral neuropathy. ^[6]
• Overdiagnosis and overtreatment: the commonest "complication" of PSA testing. Many screen-detected cancers would never have caused symptoms, and treating them causes harm without benefit.

Prognosis depends on risk group, treatment received and the biology of the tumour rather than size alone. After radical treatment, disease-specific survival is very high for low- and intermediate-risk disease (96.9% at 15 years for active monitoring in ProtecT, and 97.8% and 97.1% for prostatectomy and radiotherapy). High-risk and locally advanced disease treated with radical radiotherapy plus 3 years of ADT or prostatectomy carries a substantially higher risk of recurrence. In metastatic castration-sensitive disease, adding docetaxel or an androgen receptor inhibitor to ADT improves progression-free and overall survival. Once the disease is castration-resistant, sequential systemic therapies can maintain disease control for years, but it is eventually fatal; median overall survival in trials of first-line castration-resistant therapy is typically in the range of 2 to 3 years. ^[6]

There is no population screening programme in most countries because the benefit is small and the harm from overdiagnosis is substantial. The best-studied data come from the ERSPC, which, after 23 years, showed that 456 men aged 55 to 69 years need to be screened and 12 cancers need to be diagnosed and treated to prevent one prostate cancer death, with the numbers needed to screen and to treat falling as follow-up lengthens. Whether screening reduces all-cause mortality has not been shown. ^[2][7]

The USPSTF, after this evidence, recommends that for men aged 55 to 69 years the decision to undergo periodic PSA-based screening should be an individual one, taken after discussion of the small benefit and the real harms (false positives, biopsies, overdiagnosis, treatment complications such as incontinence and erectile dysfunction), and incorporating the man's values and preferences. Clinicians should not screen men who do not express a preference for screening, and should not screen men aged 70 years or older. Risk assessment weighs older age, African American race and family history. ^[7]

The EAU, in contrast, supports individual early detection rather than population screening, and organises it by risk. PSA testing can be recommended starting at age 50 for men without other risk factors; at 45 for men with a family history of prostate cancer (affected relative under 60) or men of African descent; and at 40 for men carrying BRCA2 mutations. Men with a baseline PSA below 1 ng per mL at age 40, or below 2 ng per mL at age 60, are at low long-term risk, and retesting can be postponed up to 8 years. Men with a PSA above 1 ng per mL at 40, or above 2 ng per mL at 60, should be retested every 2 years. Asymptomatic men with a life expectancy of less than 15 years are unlikely to benefit from early detection. Baseline PSA predicts prostate cancer mortality after 12 to 20 years, and follow-up intervals of 8 to 10 years can be considered for men up to 60. ^[2]

Risk-stratified practice in this country follows local guidance.

Population screening before the use of MRI (the ERSPC and comparable trials, which used only PSA and systematic biopsy) has the strongest evidence of benefit, and modern screening pathways incorporating MRI and targeted biopsies reduce unnecessary biopsies and overdiagnosis of insignificant cancer while maintaining detection of clinically significant cancer, although long-term mortality evidence for these newer pathways does not yet exist. ^[2]

Secondary prevention amounts to active treatment of the disease with intent, plus avoidance of overdiagnosis. Primary prevention has been disappointing: no dietary, drug or lifestyle measure has solid evidence of preventing prostate cancer, and 5-alpha-reductase inhibitors have not been approved for this purpose. ^[1]

• Older men. Life expectancy and comorbidity, not age alone, should drive management. A prognosis of more than 10 years is generally needed for local treatment to confer a cancer-specific benefit. The G8, mini-COG and Clinical Frailty Scale tools can identify frailty, and frail men may receive adapted treatment or palliation. Older men with metastatic disease on ADT need particular attention to metabolic and cardiovascular complications.
• African ancestry. Men of African ancestry have higher incidence and mortality in Western countries. Shared decision making should start earlier for those who wish it, and the USPSTF notes that models suggest possible benefit from beginning screening before age 55 in this group, without trial evidence. ^[7]
• Carriers of BRCA2 and other repair gene mutations. These men have a higher risk of aggressive disease and should begin PSA testing at 40. Germline testing is also recommended for men with metastatic disease, and after somatic HRR mutations are found. ^[1][2]
• Fertility should be discussed before radical treatment: sperm storage should be offered because prostatectomy and long-term ADT impair fertility and ejaculation.
• Hereditary and familial disease. Men with multiple first-degree relatives, or a close relative diagnosed before 55, should be informed earlier and followed more intensively.

• Many of the cheap tests are already available: digital rectal examination, total PSA, and abdominal or transrectal ultrasound. Multi-parametric MRI and targeted biopsies may not be available, and the PSA density can still be approximated using transabdominal ultrasound prostate volume.
• Where MRI or targeted biopsy is unavailable, a 12-core systematic TRUS-guided biopsy remains a reasonable diagnostic route; management then still follows the risk group logic on the basis of what is found.
• ADT by bilateral orchidectomy or long-acting GnRH injection is often the most practical palliative treatment where radiotherapy is distant. Flare should be avoided by orchidectomy or an antagonist where possible.
• Bone scan may be unavailable; symptom-directed palliative radiotherapy or bisphosphonates can still be arranged through referral.
• Access to modern drugs (abiraterone, enzalutamide, docetaxel, radium-223, olaparib) is often limited. Intermittent ADT, well-trained palliative care, good analgesia, weight-bearing exercise and calcium/vitamin D are comparatively inexpensive and still reduce suffering.
• Screening should not be pursued as a population programme; redirect resources to treating men who already have symptoms and to high-value components such as accurate diagnosis and palliative care.

• Prostate cancer is the second most commonly diagnosed cancer in men, with about 1.46 million new diagnoses and 396,792 deaths in 2022. ^[1]
• Localised disease is almost always silent; symptoms arise only with local progression or metastasis, most often to bone. ^[2]
• PSA is prostate-specific, not cancer-specific; benign disease and 5-alpha-reductase inhibitors alter its value. ^[2]
• Modern diagnosis runs PSA (and digital rectal examination) to MRI, then MRI-targeted (plus systematic) biopsy; the grade is reported with the five-group ISUP system. ^[2][3]
• Risk is stratified into low, favourable and unfavourable intermediate, high and locally advanced (EAU), or the Cambridge Prognostic Groups (NICE). ^[3][6]
• Low-risk disease is managed with active surveillance, not immediate treatment. ^[4][6]
• Radical prostatectomy or radical radiotherapy (60 Gy in 20 fractions or 74 Gy in 37 fractions) cures localised disease; radiotherapy is combined with 6 months of ADT for CPG 2 to 5 (and up to 3 years for CPG 4 to 5). ^[6]
• Docetaxel 75 mg per m2 every 3 weeks for six cycles is added in selected high-risk non-metastatic disease, and for newly diagnosed metastatic disease. ^[6]
• ADT uses GnRH agonists (leuprolide depot injections given every 1 to 6 months depending on the formulation) or antagonists, plus antiandrogens; agonists cause an initial testosterone surge of about 50% above baseline. ^[11]
• In metastatic castration-resistant disease, enzalutamide 160 mg daily, abiraterone 1000 mg daily plus prednisone 5 mg twice daily, radium-223 55 kBq per kg every 4 weeks for six doses and olaparib 300 mg twice daily (for HRR-mutated disease) are standard options, given with continued ADT. ^[8][10]
• Bone health is monitored from the start of ADT with DEXA, and denosumab 120 mg subcutaneously every 4 weeks (or bisphosphonates) is used for bone metastases to prevent skeletal-related events. ^[5][6][9]
• Biochemical recurrence after prostatectomy is best predicted above 0.4 ng per mL of PSA; salvage radiotherapy, not immediate hormones, is the standard response. ^[5][6]
• Men with metastatic disease (especially with spine involvement) must be educated about spinal cord compression and the urgent need to seek care. ^[5][11]
• USPSTF screening is a shared decision for men 55 to 69 years and is not recommended at 70 or older; EAU recommends individual early detection by risk group. ^[2][7]

Prostate cancer is discussed here in relation to urinary incontinence, nephrolithiasis, polycystic kidney disease, hydronephrosis, acute kidney injury, chronic kidney disease, hypercalcaemia and hypertension topics elsewhere in this library, in plain text rather than as links until those pages are verified. Useful neighbouring reading includes renal cell carcinoma, acid-base and electrolyte disorders, and the urinary tract infection topic.