Prostate Cancer

Overview

Prostate cancer is the most common cancer in men and the second most common cancer in the UK. Up to 1 in 8 people will develop prostate cancer in their life.

Nearly all (95%) prostate cancers are adenocarcinomas (cancers of glandular tissue). Most prostate cancers are indolent and slow growing, but some can be aggressive. The most common sites of metastasis are the bone and lymph nodes.

Definitions

Localised prostate cancer – cancer confined within the prostate capsule and rarely causes symptoms.

Locally advanced prostate cancer – cancer extends beyond the prostate capsule and is often asymptomatic when diagnosed.

Metastatic prostate cancer – cancer that has spread beyond the prostate to distant tissues, most often the bones and lymph nodes, resulting in pain and fragility fractures.

Epidemiology

• Prostate cancer is the second most common cancer in the UK
• Up to 1 in 8 people develop prostate cancer at some point in their life
• The most common age of diagnosis is 65-70 years old
• Incidence and mortality are higher in people of black ethnicity and lower in Asian people
• Prostate cancer can also affect trans women as the prostate is generally conserved after gender-affirming surgery

Risk Factors

Although the exact cause of prostate cancer is unknown, the following risk factors have been identified:

• Increasing age – one of the strongest risk factors:
  • Some autopsy studies have shown that by 80 years of age, 70% of people have evidence of prostate cancer
• Black ethnicity – incidence and mortality rates are higher, with a lifetime risk of 1 in 4 compared to 1 in 8 in white people
• Family history

Presentation

Overview

In early stages, localised prostate cancer is asymptomatic. However, as it progresses, more symptoms can arise:

• Features of locally advanced prostate cancer:
  • Lower urinary tract symptoms (LUTS) – storage, voiding, post-micturition
    • These symptoms are common in older people and are non-specific
  • Pelvic pain
• Features of metastatic disease:
  • Pain in the lower back or bones – suggests bone metastases
  • Spinal cord compression and cauda equina syndrome may occur
• Other unexplained features:
  • Constitutional symptoms – such as unexplained weight loss, lethargy, anorexia, and night sweats
  • Haematuria
  • Erectile dysfunction

Examination findings

A digital rectal examination (DRE) should be performed. If the prostate feels hard, asymmetrical, craggy/nodular, or irregular with loss of the median sulcus, prostate cancer may be likely. A normal gland does not exclude prostate cancer.

Prostate-Specific Antigen (PSA) Testing

Overview

Prostate-specific antigen (PSA) is an protein produced in the prostate to liquefy semen and allow sperm to move freely. It is mainly secreted into prostatic fluid and semen, however, small amounts are present in the blood.

In disorders of the prostate (including, but not restricted to, prostate cancer), blood PSA levels can be elevated as PSA leaks out of the prostate.

It is relatively inaccurate for prostate cancer because cancer can be present without elevated PSA and many other conditions and factors can result in elevated PSA. This can lead to high false positive rates leading to unnecessary investigations and treatment, along with false negative rates giving false reassurance. 

Patients should be given thorough counselling before offering a PSA test including information regarding its benefits, limitations, and risks. These are discussed more in NICE CKS.

Factors affecting PSA

Some factors that can increase serum PSA can include:

• Benign prostatic hyperplasia
• Infections including prostatitis and urinary tract infection – delay PSA measurement for 6 weeks
• Ejaculation, vigorous exercise, receptive anal intercourse – delay PSA measurement for at least 48 hours
• Prostate biopsy within the last 6 weeks
• Digital rectal examination (DRE) – this is controversial and whether it elevates PSA or not is up for debate. Many clinicians do the blood test before a DRE or wait for 1 week before measuring afterwards

Referral and Investigations

Referral

Urgently refer via a suspected cancer pathway if the prostate feels malignant on DRE.

Consider an urgent referral via a suspected cancer pathway if PSA levels are above the threshold for the patient’s age. These can be found in the NICE guidelines for prostate cancer.

Investigations

Key investigations include:

• Multiparametric MRI is the first-line investigation before a biopsy:
  • The results are reported on a 5-point Likert scale
• Pre-biopsy PSA:
  • If not already performed
• Prostate biopsy:
  • If Likert scale ≥3, offer a prostate biopsy
  • If Likert scale is 1-2, discuss the advantages/disadvantages of the prostate biopsy and reach a shared decision

Scoring

The Gleason grading system grades prostate cancer based on histology and guides treatment. Two scores are recorded and added, the first number is the grade of the most prevalent pattern in the biopsy, and the second number is the second most prevalent pattern.

A score if 2 is the most-well differentiated and a score of 10 is the most poorly differentiated. Higher scores are associated with a worse prognosis.

Management

Overview

Management is coordinated by a multidisciplinary team and depends on the grade and stage of the cancer, and the patient’s life expectancy and comorbidities.

Some management steps may involve:

• Localised prostate cancer may involve:
  • Watchful waiting
  • Radical prostatectomy – may lead to erectile dysfunction and urinary incontinence
  • Radiotherapy – external beam or brachytherapy
• Locally advanced prostate cancer may involve:
  • Methods to reduce androgens such as:
    • Gonadotropin-releasing hormone (GnRH) agonists (e.g. goserelin):
      • Initially, they increase androgen levels but cause overstimulation, resulting in androgen secretion decreasing over time and eventually stopping
      • A tumour flare may occur during the period when androgens increase, therefore anti-androgen ‘cover’ therapy may be given
    • Bicalutamide – a non-steroidal anti-androgen that blocks androgen receptors
    • Abiraterone – an androgen synthesis inhibitor
    • Bilateral orchidectomy – rarely done
  • Radical prostatectomy
  • Radiotherapy – external beam or brachytherapy

Chemotherapy with docetaxel may be used.

Complications

• Local invasion – prostate cancer can spread to the seminal vesicles, bladder, urethra, or other side of the pelvis, resulting in symptoms such as LUTS
  • By the time LUTS are present, prostate cancer may be advanced and incurable
• Metastasis – commonly to the bones where they can cause bone pain, fractures, or spinal cord compression

Prognosis

• If diagnosed in early stages, prostate cancer has a 5-year survival rate of >90%
• For those with metastatic prostate cancer, 5-year survival rates decrease to 49%