Prostate Cancer

Prostate cancer is a malignant tumour arising from the epithelial cells of the prostate gland. It is one of the most common cancers affecting men and occurs predominantly in older males, particularly those above 50 years of age.

The disease has a variable clinical course, ranging from slow-growing tumours that may remain clinically insignificant to aggressive cancers with early metastatic spread. The axial skeleton (spine, pelvis, and ribs) is the most common site of distant metastasis.

Early prostate cancer is frequently asymptomatic and may be detected through abnormal prostate-specific antigen (PSA) levels or digital rectal examination (DRE). Lower urinary tract symptoms and urinary retention are uncommon in early disease because the tumour usually originates in the peripheral zone of the prostate rather than the transition zone.

Epidemiology

Prostate cancer incidence increases significantly with advancing age and is uncommon before the age of 50 years. It is among the leading causes of cancer-related morbidity and mortality in men worldwide.

Most cases occur in older men, and the majority are diagnosed after 50 years of age. The burden is expected to increase with population ageing.

Approximately 20% of patients may present with systemic manifestations such as weight loss and bone pain, particularly in advanced disease.

Risk factors

Non-modifiable risk factors

• Increasing age

• Family history of prostate cancer

• Genetic predisposition

• African ancestry

Modifiable or associated risk factors

• Obesity

• High-fat dietary patterns

• Reduced physical activity

• Metabolic syndrome

• Chronic inflammation of the prostate

Pathophysiology

Prostate cancer develops due to malignant transformation of prostate epithelial cells, resulting in uncontrolled cellular proliferation and tumour formation.

Most prostate cancers arise from the peripheral zone of the prostate. As the tumour progresses, it may invade surrounding tissues and spread through lymphatic and blood vessels.

The axial skeleton is the most common site of metastasis because prostate cancer cells have a tendency to spread to bone, causing osteoblastic metastatic lesions. Advanced disease may also spread to pelvic lymph nodes and other distant organs.

Tumour progression may lead to increased production of prostate-specific antigen (PSA), although PSA levels vary and do not always correlate perfectly with disease severity.

Clinical presentation

Prostate cancer is often asymptomatic in early stages. Symptoms usually develop when the tumour enlarges, invades surrounding structures, or metastasizes.

Symptoms

Local symptoms

• Difficulty urinating

• Weak urinary stream

• Urinary frequency

• Nocturia

• Urinary hesitancy

• Urinary retention (usually uncommon in early disease)

Systemic symptoms

• Weight loss

• Fatigue

• Loss of appetite

• General weakness

Symptoms due to metastasis

• Bone pain, especially back pain

• Hip pain

• Pathological fractures

• Lower limb swelling due to lymphatic obstruction

Clinical signs

Digital rectal examination

Findings suggestive of prostate cancer include:

• Hard prostate gland

• Nodular prostate surface

• Irregular prostate enlargement

• Obliterated median sulcus

Features of advanced disease

• Lower limb lymphoedema due to lymph node metastases

• Bone tenderness

• Neurological symptoms from spinal metastases

• Signs of metastatic disease

Diagnostic criteria

Diagnosis of prostate cancer requires histological confirmation.

Diagnostic evaluation includes:

• Suspicious findings on digital rectal examination

• Elevated PSA levels

• Prostate imaging where available

• Prostate core biopsy for definitive diagnosis

Important note regarding PSA interpretation

PSA results should be interpreted carefully because:

• PSA has limited sensitivity.

• Some patients with prostate cancer may have PSA levels below 4 ng/mL.

• PSA may be elevated in conditions other than cancer, including benign prostatic hyperplasia and prostatitis.

Investigations

Prostate-specific antigen (PSA)

PSA is used for:

• Detection of possible prostate cancer

• Risk assessment

• Monitoring treatment response

PSA is often elevated in prostate cancer and may be markedly increased in metastatic disease.

Digital rectal examination

Used to identify:

• Abnormal prostate consistency

• Nodules

• Irregular enlargement

Prostate biopsy

• Prostate core biopsy confirms the diagnosis.

• Histological examination determines tumour grade and aggressiveness.

Imaging investigations

Imaging may be used for staging and assessment of metastatic disease.

Possible investigations include:

• Transrectal ultrasound

• Multiparametric MRI of the prostate

• Bone scan for suspected skeletal metastases

• CT scan or MRI for lymph node and metastatic assessment

Management

Management depends on:

• Stage of disease

• Tumour risk category

• PSA level

• Histological grade

• Patient age

• Life expectancy

• Patient preference

Treatment options include surveillance, surgery, androgen deprivation therapy, and chemotherapy.

Non-pharmacological treatment

Early disease

Watchful waiting

Appropriate for:

• Low-risk patients

• Short life expectancy

• Significant comorbidities

The aim is symptom control rather than curative treatment.

Active surveillance

Appropriate for:

• Patients with the lowest risk of cancer progression

• Life expectancy greater than 10 years

Patients require regular monitoring with:

• PSA testing

• Clinical review

• Repeat biopsy or imaging when indicated

Radical prostatectomy

Indicated for:

• Localized prostate cancer

• Patients with life expectancy greater than 10 years

The procedure involves complete surgical removal of the prostate gland.

Advanced disease

Surgical androgen deprivation therapy

• Bilateral orchidectomy may be performed for advanced prostate cancer.

This reduces testosterone production and slows tumour progression.

Pharmacological treatment

Medical androgen deprivation therapy is indicated in patients with:

• Advanced prostate cancer

• PSA levels greater than 50 ng/mL

• Poorly differentiated tumours

• Patients unsuitable for local curative treatment

Late disease

Luteinizing hormone-releasing hormone (LHRH) agonists

• Goserelin 3.6 mg subcutaneously every week.

OR

• Goserelin 10.8 mg subcutaneously every 12 weeks.

Anti-androgen therapy

• Bicalutamide 50–150 mg orally once daily.

Combined androgen blockade

For patients who fail the above options:

• LHRH agonist combined with bicalutamide 50 mg orally once daily.

Castrate-resistant prostate cancer

For patients whose disease progresses despite androgen deprivation:

• Docetaxel 75 mg/m² intravenously every 3 weeks.

Management according to underlying cause

Localized prostate cancer

Management options include:

• Active surveillance for very low-risk disease

• Radical prostatectomy for suitable candidates

• Specialist oncology/urology assessment

Advanced metastatic prostate cancer

Management includes:

• Androgen deprivation therapy

• Management of metastatic complications

• Pain control

• Oncology follow-up

Bone metastases

Management may include:

• Analgesia

• Prevention of skeletal complications

• Specialist oncology management

Referral

Referral to an oncologist or urologist is required for:

• All patients with suspected prostate cancer

• Abnormal digital rectal examination

• Elevated PSA requiring further assessment

• Confirmed prostate cancer

• Evidence of metastatic disease

• Treatment planning and specialist management

Complications

• Bone metastases

• Pathological fractures

• Spinal cord compression

• Chronic bone pain

• Urinary obstruction

• Urinary retention

• Renal impairment due to obstruction

• Lymphoedema

• Anaemia

• Treatment-related complications

Prognosis

The prognosis depends mainly on tumour stage, grade, PSA level, and presence of metastases.

Localized prostate cancer often has excellent outcomes with appropriate treatment. Advanced metastatic disease is usually not curable but can often be controlled for prolonged periods with androgen deprivation therapy and other systemic treatments.

Early diagnosis and appropriate risk-based management improve survival and quality of life.

Prevention

There is no guaranteed method to prevent prostate cancer; however, risk may be reduced through:

• Maintaining healthy body weight

• Regular physical activity

• Healthy dietary patterns

• Avoiding tobacco use

• Regular medical assessment for men at increased risk

• Early evaluation of urinary symptoms

• Appropriate screening discussions based on age and risk factors