Prostate Cancer — Symptoms, Causes & Treatment | MyMedicPlus

Prostate cancer is the most common non-skin cancer in men worldwide, with over 1.4 million new cases diagnosed annually and the second most common cause of cancer death in men in most high-income countries. It arises from the epithelial cells of the prostate's peripheral zone in approximately 70–80% of cases. Prognosis varies enormously — from slow-growing, clinically indolent, well-differentiated low-risk disease that can be safely managed with active surveillance without immediate curative treatment — to aggressive, high-grade, locally advanced, or metastatic disease requiring multimodal systemic therapy. The Gleason grading system (reported as Grade Groups 1–5 based on architectural patterns of the tumour on prostate biopsy) and clinical risk stratification (low, intermediate, high-risk, locally advanced, metastatic) guide all management decisions. Five-year relative survival for localised prostate cancer exceeds 99% with appropriate treatment. For metastatic disease, survival has improved dramatically with modern next-generation hormonal therapies (abiraterone, enzalutamide) and PSMA-targeted radioligand therapy, though it remains a terminal diagnosis for many men. Screening with PSA blood testing remains controversial given the risk of overdiagnosis of clinically insignificant cancers.

Advancing age is the strongest risk factor — incidence rises sharply after 50, with most cases diagnosed between 65–74 years, and fewer than 1% diagnosed under 40. Family history: a first-degree male relative (father or brother) with prostate cancer doubles the lifetime risk; BRCA2 pathogenic variants increase lifetime risk 8-fold and are strongly associated with aggressive, early-onset disease; BRCA1 variants increase risk approximately 2-fold. Lynch syndrome (mismatch repair gene mutations — MLH1, MSH2, MSH6, PMS2) confers elevated prostate cancer risk. Ethnicity: Black African and Black Caribbean men have approximately 2–2.5x higher incidence than White men, present at a younger age, and have worse stage-adjusted outcomes; Asian men (South and East Asian) have the lowest global incidence. Obesity is associated with more aggressive and lethal prostate cancer at diagnosis — not simply increased incidence; obese men are also more likely to have biochemical recurrence after treatment. High animal fat and red meat consumption shows epidemiological associations. Occupational cadmium exposure (welders, battery manufacturing workers) is a recognised risk factor. Exogenous androgen use (anabolic steroids, testosterone supplementation) is associated with elevated prostate cancer risk and can accelerate growth of pre-existing androgen-sensitive tumours. Chronic prostatic inflammation may contribute to carcinogenesis via inflammatory cytokine pathways. Vasectomy: some epidemiological evidence for a modest increased risk, but association remains weak and contested.

Early-stage, localised prostate cancer is typically completely asymptomatic — this is the key challenge of the disease and the rationale for PSA screening. Most early prostate cancers are detected only by a raised PSA on a blood test. As disease progresses locally to involve or compress the urethra, obstructive lower urinary tract symptoms appear — these overlap significantly with benign prostatic hyperplasia (BPH): hesitancy (difficulty initiating urination), a weak or intermittent urinary stream, increased daytime frequency, nocturia (waking at night to void), urgency, difficulty fully emptying the bladder, and terminal dribbling. Haematuria (blood in urine — painless, visible) and haematospermia (blood in semen) occur with more locally advanced or invasive disease. Pelvic, perineal, or rectal discomfort develops with local invasion of adjacent structures. Bone pain — particularly in the lower back, pelvis, hips, and femora — is the most common symptom of skeletal metastases (prostate cancer metastatises preferentially to the axial skeleton via haematogenous and lymphatic routes). Pathological fractures through bone metastases and hypercalcaemia occur with advanced bony disease. Spinal cord compression from vertebral metastases (back pain, leg weakness, numbness, bladder or bowel dysfunction) is a neurosurgical emergency. Systemic symptoms of advanced metastatic cancer — anorexia, weight loss, profound fatigue, cachexia, and anaemia — appear in the later stages.

PSA (prostate-specific antigen) is a serine protease produced exclusively by prostate epithelium — present at low concentrations in blood in normal men; elevated PSA (typically above 4 ng/mL, or above age-specific reference ranges — above 3.0 ng/mL in men aged 50–69) warrants further investigation, though it is not diagnostic alone and can be elevated by BPH, prostatitis, recent ejaculation, or urethral instrumentation. Free-to-total PSA ratio below 15–25% increases likelihood of malignancy over BPH. Digital rectal examination (DRE) assesses prostate symmetry and consistency — hard, nodular, or irregular prostate texture is suspicious for malignancy. Multiparametric MRI (mpMRI — combining T2-weighted, diffusion-weighted, and dynamic contrast-enhanced sequences) of the prostate, reported using PI-RADS v2.1 scoring (1–5: 1–2 low probability, 3 equivocal, 4–5 high probability of clinically significant cancer) should precede biopsy in most pathways (NICE-recommended) — reduces unnecessary biopsy for low-risk findings. Prostate biopsy (transperineal route preferred over TRUS to reduce infection risk) provides histological diagnosis — MRI-targeted biopsy of PI-RADS 3–5 lesions plus systematic cores. Gleason grading assigns Grade Group 1 (Gleason 3+3=6 — lowest) through Grade Group 5 (Gleason 4+5=9 or 5+5=10 — highest). Staging workup for intermediate-high risk disease: PSMA-PET-CT (gallium-68 or fluorine-18 PSMA — most sensitive staging modality, detects nodal and distant metastases at very low PSA levels); CT chest/abdomen/pelvis; bone scan if PSMA-PET unavailable.

Low-risk disease (Grade Group 1, PSA below 10 ng/mL, clinical T1c–T2a): active surveillance (AS) is the preferred strategy — PSA monitoring every 3–6 months, mpMRI annually, and repeat transperineal biopsy at 12–18 months and every 2–3 years thereafter; approximately 50% eventually require curative treatment; AS avoids treatment side effects in the majority who have truly indolent disease. Intermediate-risk disease: radical prostatectomy (robot-assisted radical prostatectomy — RARP — laparoscopic, minimally invasive approach with bilateral nerve-sparing where feasible; pelvic lymph node dissection in unfavourable intermediate and high-risk disease) OR definitive external beam radiotherapy (IMRT/IGRT — 5-week hypofractionated regimen; stereotactic body radiotherapy in 5 fractions for low-intermediate risk) plus 6 months of androgen deprivation therapy. Brachytherapy (permanent low-dose-rate iodine-125 seed implantation or high-dose-rate temporary brachytherapy boost) for favourable intermediate-risk disease. High-risk or locally advanced disease: combination EBRT plus long-term ADT for 2–3 years (LHRH agonists: leuprorelin, goserelin administered 3-monthly; or LHRH antagonists: degarelix, relugolix — no testosterone flare risk) — significantly superior to either alone (SPCG-7, DART 01/05 trials). Radical prostatectomy with extended pelvic lymph node dissection, with adjuvant or salvage radiotherapy as needed. Metastatic hormone-sensitive prostate cancer (mHSPC): ADT plus doublet therapy (docetaxel 75 mg/m2 6 cycles, or a next-generation androgen receptor pathway inhibitor: abiraterone acetate 1000 mg + prednisolone; enzalutamide; apalutamide; darolutamide) — triplet therapy (ADT + docetaxel + NGAPI) is now standard for high-volume metastatic disease. Castrate-resistant prostate cancer (CRPC): enzalutamide, abiraterone, docetaxel, cabazitaxel; olaparib or rucaparib (PARP inhibitors) for BRCA1/2-mutated CRPC; radium-223 for bone-predominant metastatic CRPC; Lutetium-177-PSMA radioligand therapy (Pluvicto) for PSMA-positive metastatic CRPC — approved by FDA 2022 and NICE 2023.

Post-radical prostatectomy: urinary incontinence (stress incontinence from sphincter disruption — temporary in most, resolving by 12 months in approximately 90%; persistent pad-dependent incontinence in 5–10% requiring pelvic floor physiotherapy, urethral sling, or artificial urinary sphincter); erectile dysfunction (affects 30–80% depending on nerve-sparing technique, age, and pre-operative baseline function — managed with PDE5 inhibitors, vacuum erection devices, or intracavernosal alprostadil). Radiotherapy complications: radiation proctitis (rectal bleeding, diarrhoea, urgency — late in 5–10%); radiation cystitis (haematuria, frequency); urethral stricture; late secondary malignancy risk (bladder, rectal). Androgen deprivation therapy (ADT) — systemic complications: osteoporosis and fragility fractures (prevent with denosumab 60 mg 6-monthly or zoledronic acid — NICE recommended for men on long-term ADT); metabolic syndrome (weight gain, central adiposity, dyslipidaemia, insulin resistance, type 2 diabetes — monitor glucose, lipids annually); cardiovascular events (elevated with long-term ADT — careful monitoring in those with pre-existing CVD); hot flushes (treat with venlafaxine 37.5 mg or acupuncture); sexual dysfunction and loss of libido; fatigue; gynaecomastia (tamoxifen 10 mg daily is effective prophylaxis and treatment); and mood disturbance including depression. Spinal cord compression from vertebral bone metastases — a neurosurgical emergency requiring urgent high-dose dexamethasone (16 mg daily), MRI whole spine, and radiotherapy or surgical decompression within 24 hours.

PSA screening is recommended — following an informed shared decision-making discussion about benefits and limitations — from age 50 for average-risk men; from age 45 for Black men and those with a first-degree male relative with prostate cancer; from age 40 for those with a known BRCA2 mutation or two or more first-degree relatives with prostate cancer. A Mediterranean diet rich in vegetables, lycopene (cooked tomatoes — particularly tomato paste and passata), omega-3 fatty acids, green tea polyphenols, and soy isoflavones may modestly reduce prostate cancer incidence or aggressiveness. Regular physical activity and maintaining a healthy BMI are associated with reduced risk of aggressive and lethal prostate cancer. Avoid exogenous androgen use (anabolic steroids, testosterone supplementation without medical indication). Men with a pathogenic BRCA1 or BRCA2 variant should have enhanced annual PSA screening from age 40, with low threshold for referral to urology, and genetic counselling for family members. After active surveillance: strict protocol adherence is essential — do not miss PSA checks, MRI reviews, or biopsy appointments, as the safety of AS depends entirely on rigorous monitoring. After curative treatment: PSA should be monitored every 3–6 months for 2 years, then 6-monthly for a further 3 years, then annually; a rising PSA (above 0.2 ng/mL post-prostatectomy, or above nadir plus 2 ng/mL post-radiotherapy) defines biochemical recurrence requiring specialist review.

See your GP if you develop lower urinary tract symptoms — particularly hesitancy (difficulty starting to urinate), a weak or interrupted urine stream, increased frequency (especially at night — nocturia), urgency, or incomplete bladder emptying — in a man over 50. While these symptoms are most commonly caused by benign prostatic hyperplasia, prostate cancer must be considered. Request a PSA blood test discussion if you are: aged over 50 (any race), aged 45 or over with a first-degree relative with prostate cancer, or aged 40 or over if Black (significantly higher lifetime risk). Seek urgent assessment for: bone pain (particularly lower back, pelvis, or hips) persisting in a man over 50 — bone metastases from prostate cancer must be excluded; blood in the urine or semen; new-onset erectile dysfunction in a previously potent man over 50; and leg weakness or lower limb numbness with urinary or bowel problems (possible spinal cord compression from vertebral metastases — emergency MRI required). Men under active surveillance (watchful waiting) for prostate cancer should contact their urology team if they experience any new symptoms, as this may signal disease progression.