Carcinoma of the prostate is the most common malignant tumour of the prostate gland and one of the leading cancers affecting men worldwide. Approximately 95% of prostate cancers are adenocarcinomas arising from the glandular epithelium of the prostate.

The disease ranges from indolent localized tumours to aggressive metastatic cancer. Management is guided by tumour stage, Gleason score, prostate-specific antigen (PSA) level, life expectancy, performance status, and comorbidities.

Patients are commonly stratified into prognostic risk groups to guide treatment decisions:

Low-risk disease

• T1–T2a

• PSA <10 ng/mL

• Gleason score ≤6

Intermediate-risk disease

• T2b

• PSA 10–20 ng/mL

• Gleason score 7

High-risk disease

• T2c–T4

• PSA >20 ng/mL

• Gleason score 8–10

Epidemiology

Prostate cancer is one of the most common cancers among men globally.

Epidemiological characteristics include:

• Primarily affects men older than 50 years

• Incidence increases with age

• Higher incidence among men with a family history of prostate cancer

• Adenocarcinoma accounts for approximately 95% of cases

• Bone is the most common site of distant metastasis

Risk factors

Increasing age

The strongest risk factor with incidence increasing significantly after 50 years of age.

Family history

Risk is increased in men with:

• First-degree relatives affected by prostate cancer

• Multiple affected family members

Genetic factors

Including inherited mutations involving:

• BRCA1

• BRCA2

• HOXB13

Ethnicity

Certain populations have higher incidence and mortality rates.

Diet and lifestyle factors

Associated factors include:

• High-fat diet

• Obesity

• Sedentary lifestyle

• Low intake of fruits and vegetables

Hormonal influences

Androgen stimulation plays a central role in prostate cancer development and progression.

Pathophysiology

Most prostate cancers originate from glandular epithelial cells in the peripheral zone of the prostate.

The disease develops through:

1. Genetic and epigenetic alterations

2. Prostatic intraepithelial neoplasia

3. Localized adenocarcinoma

4. Local invasion

5. Regional lymph node spread

6. Distant metastasis

Tumour growth is largely dependent on androgen receptor signaling.

Common sites of metastasis include:

• Bone

• Lymph nodes

• Liver

• Lung

Bone metastases are typically osteoblastic and may cause severe pain and pathological fractures.

Clinical presentation

Early prostate cancer is frequently asymptomatic and may be detected during evaluation of elevated PSA levels or abnormal digital rectal examination findings.

Symptoms generally develop with locally advanced or metastatic disease.

Symptoms

Lower urinary tract symptoms

• Urinary frequency

• Nocturia

• Hesitancy

• Poor urinary stream

• Terminal dribbling

• Incomplete bladder emptying

Sexual symptoms

• Reduced potency

• Erectile dysfunction

Symptoms of locally advanced disease

• Urinary retention

• Hematuria

• Pelvic discomfort

Symptoms of metastatic disease

• Bone pain

• Back pain

• Pathological fractures

• Weight loss

• Fatigue

• Weakness

Symptoms of spinal cord compression

• Back pain

• Limb weakness

• Sensory deficits

• Bladder dysfunction

Clinical signs

Digital rectal examination (DRE) findings

• Hard prostate

• Irregular prostate surface

• Nodular prostate

• Fixed prostate

• Loss of normal median sulcus

General findings

• Weight loss

• Cachexia

• Reduced performance status

Signs of metastatic disease

• Bone tenderness

• Pathological fractures

• Spinal cord compression

• Lymphadenopathy

Differential diagnosis

• Benign prostatic hyperplasia (BPH)

• Prostatitis

• Prostatic abscess

• Bladder cancer

• Urethral stricture disease

• Neurogenic bladder

• Metastatic carcinoma involving the prostate

Diagnostic criteria

Prostate cancer should be suspected in men presenting with:

• Elevated PSA level

• Abnormal digital rectal examination

• Progressive lower urinary tract symptoms

• Unexplained bone pain

• Pathological fractures

• Features of metastatic disease

Definitive diagnosis requires:

• Histopathological confirmation from prostate biopsy or tissue obtained during transurethral resection of the prostate (TURP)

Screening for prostate cancer

Routine population screening is not universally recommended.

When screening is undertaken:

• PSA testing and digital rectal examination should begin at age 50 years in men with a life expectancy greater than 10 years

• Screening of high-risk individuals should begin at age 45 years

High-risk groups include:

• Men with a family history of prostate cancer

• Men with known hereditary cancer syndromes

Investigations

Laboratory investigations

Full blood count (FBC)

Used to assess:

• Anaemia

• Baseline treatment status

Liver function tests (LFTs)

Assess hepatic function and possible liver metastases.

Renal function tests

Including:

• Urea

• Creatinine

Serum prostate-specific antigen (PSA)

Used for:

• Diagnosis

• Risk stratification

• Monitoring treatment response

• Detection of recurrence

Serum alkaline phosphatase (ALP)

May be elevated in bone metastases.

Serum testosterone

Useful before initiation of androgen deprivation therapy.

Imaging investigations

Plain X-rays of painful bones or spine

Useful for evaluating:

• Bone metastases

• Pathological fractures

Chest X-ray (CXR)

Assesses pulmonary metastases.

Abdominal and pelvic ultrasound

Evaluates:

• Prostate size

• Urinary tract obstruction

• Metastatic disease

CT scan of abdomen and pelvis

Used for:

• Local staging

• Nodal assessment

• Detection of metastatic disease

Pelvic MRI

Recommended in early-stage disease for:

• Local tumour staging

• Assessment of extracapsular extension

• Surgical planning

PET/CT

Useful in selected patients for advanced disease evaluation.

Bone scan

Recommended when:

• PSA is significantly elevated

• Bone pain is present

• High-risk disease is suspected

Histopathology

Prostate biopsy

Required for definitive diagnosis and Gleason grading.

TURP specimen histology

May identify incidental prostate cancer and confirm diagnosis.

Staging

Prostate cancer is staged using the TNM staging system.

Risk stratification incorporates:

• TNM stage

• PSA level

• Gleason score

Patients are classified as:

• Low risk

• Intermediate risk

• High risk

Management

Management depends on:

• Disease stage

• Risk category

• PSA level

• Life expectancy

• Performance status

• Patient preference

• Presence of comorbidities

Management options include:

• Watchful waiting

• Active surveillance

• Surgery

• Radiotherapy

• Hormonal therapy

• Chemotherapy

• Palliative care

Non-pharmacological treatment

Active surveillance

Suitable for selected patients with:

• Low-risk disease

• Long life expectancy

• Minimal symptoms

Monitoring includes:

• Serial PSA measurements

• Repeat DRE

• Repeat imaging and biopsy when indicated

Watchful waiting

Appropriate for:

• Elderly patients

• Significant comorbidities

• Limited life expectancy

Surgery

Radical prostatectomy

Indicated for:

• Low-risk disease

• Intermediate-risk disease

• Selected high-risk localized disease

Potential complications include:

• Erectile dysfunction

• Urinary incontinence

Transurethral resection of the prostate (TURP)

Indicated for:

• Relief of urinary obstruction

• Obtaining tissue for diagnosis

Bilateral orchiectomy

A form of surgical androgen deprivation therapy.

Used in:

• Locally advanced disease

• Metastatic disease

Not considered curative surgery.

Radiotherapy

Radical radiotherapy

Used as:

• Definitive treatment

• Adjuvant treatment

Recommended dose:

• External beam radiotherapy up to 74 Gy in 37 fractions using 3DCRT or IMRT techniques

Palliative radiotherapy

Indicated for:

• Bone metastases

• Massive haematuria

• Spinal cord compression

• Brain metastases

• Pain control

Pharmacological treatment

Hormonal therapy (androgen deprivation therapy)

Goserelin

Goserelin – 3.6 mg – subcutaneous – every 4 weeks

OR

Goserelin – 10.8 mg – subcutaneous – every 12 weeks

With or without:

Bicalutamide – 50 mg – oral – once daily

Treatment duration:

• Up to 2 years depending on PSA response and clinical condition

Important considerations

• Goserelin is not required after bilateral orchiectomy

• Bicalutamide may still be administered after orchiectomy

Chemotherapy for hormone-refractory prostate cancer

Docetaxel regimen

Docetaxel – 75 mg/m² – intravenous infusion over 2 hours – day 1

Frequency:

• Every 21 days

Duration:

• 6 cycles

Indication:

• Hormone-refractory prostate cancer

• Castration-resistant prostate cancer

Management of bone metastases and tumour-induced hypercalcaemia

Zoledronic acid

Zoledronic acid – 4 mg – intravenous infusion over 15 minutes – every 4 weeks

Administer together with:

• Calcium supplementation

• Vitamin D supplementation

Treatment of castration-resistant prostate cancer

Abiraterone acetate

Abiraterone acetate – 500 mg – oral – once daily with food

Administered with prednisolone according to institutional protocols.

Enzalutamide

Enzalutamide – 160 mg – oral – once daily

Management according to underlying disease stage

Low-risk disease

Management options:

• Active surveillance

• Radical prostatectomy

• Radical radiotherapy

Intermediate-risk disease

Management options:

• Radical prostatectomy

• Radical radiotherapy

• Androgen deprivation therapy where indicated

High-risk localized disease

Management options:

• Radical radiotherapy plus androgen deprivation therapy

• Radical prostatectomy in selected patients

Locally advanced disease

Management options:

• Long-term androgen deprivation therapy

• Radiotherapy

• Palliative interventions where required

Metastatic disease

Management includes:

• Lifelong androgen deprivation therapy

• Palliative radiotherapy

• Bisphosphonates

• Chemotherapy for castration-resistant disease

Castration-resistant prostate cancer

Management options include:

• Docetaxel-based chemotherapy

• Zoledronic acid

• Abiraterone acetate

• Enzalutamide

• Palliative care measures

Follow-up

Patients receiving treatment should be reviewed regularly.

Recommended monitoring

• PSA measurement every 3 months

• Clinical assessment

• Evaluation of treatment toxicity

• Imaging when clinically indicated

For castration-resistant disease:

• Monthly zoledronic acid may be administered when indicated

• Continue calcium and vitamin D supplementation

Referral

All patients with suspected or confirmed prostate cancer should be referred to specialized urology or oncology services.

Urgent referral indications

• Suspected spinal cord compression

• Pathological fractures

• Urinary retention

• Massive haematuria

• Rapidly rising PSA

• Metastatic disease

Complications

Disease-related complications

• Urinary retention

• Obstructive uropathy

• Bone metastases

• Pathological fractures

• Spinal cord compression

• Severe pain

• Anaemia

• Cachexia

Treatment-related complications

Surgery

• Urinary incontinence

• Erectile dysfunction

• Surgical complications

Hormonal therapy

• Hot flushes

• Osteoporosis

• Loss of libido

• Metabolic syndrome

Chemotherapy

• Myelosuppression

• Neuropathy

• Fatigue

• Infection

Radiotherapy

• Radiation cystitis

• Radiation proctitis

• Erectile dysfunction

Prognosis

Prognosis depends on:

• TNM stage

• Gleason score

• PSA level

• Response to therapy

• Presence of metastases

Localized disease treated with curative intent has an excellent prognosis. Advanced metastatic and castration-resistant disease is associated with reduced survival.

Prevention

Primary prevention

• Maintain healthy body weight

• Regular physical activity

• Balanced diet rich in fruits and vegetables

• Smoking cessation

Secondary prevention

• Early evaluation of urinary symptoms

• Appropriate PSA testing in selected patients

• Early assessment of high-risk individuals

Tertiary prevention

• Adherence to treatment

• Regular follow-up

• Early detection of recurrence

• Prevention of skeletal complications