urology,

Prostate Cancer

May 10, 2020

Pathology

  • Mostly adenocarcinomas
  • Arises on the peripheral zone of the prostate
  • Mostly slow-growing but some can be aggressive
  • Commonly metastesise to lymph nodes and bones

Epidemiology

  • The most common cancer in men
  • Its incidence increases with age: 20% in 50s and 70% in 70s
  • Subclinical prostate cancer is common in men aged over 50 years

Risk factors

  • Advanced age
  • Afro-Caribbean mean (increased incidence and mortality)
  • If one first-degree relative has prostate cancer, the risk is doubled
  • Food consumpution (high intake of animal fat and lower intake of fruits, cereals and vegetables)
  • Alcohol consumption
  • Pattern of sexual behaviour
  • Chronic inflammation and occupational exposure

Screening

  • No screening in the UK
    • UK Rational: only small reduction in mortality but ↑ diagnostic and treatment harms

Presentation

  • Local disease:
    • Raised PSA
    • LUTS
    • Urinary tract infection.
  • Locally invasive disease:
    • Haematuria, dysuria, incontinence.
    • Haematospermia (blood in ejaculation)
    • Perineal and suprapubic pain.
    • Obstruction of ureters, causing loin pain, anuria, symptoms of acute kidney injury or chronic kidney disease.
    • Rectal symptoms - eg, tenesmus (recurrent inclination to empty bowel)
  • Metastatic disease (think about metastasis to bones and lymph nodes):
    • Bone pain or sciatica.
    • Paraplegia secondary to spinal cord compression.
    • Lymph node enlargement.
    • Loin pain or anuria due to ureteric obstruction by lymph nodes.
    • Lethargy (anaemia, uraemia).
    • Weight loss, cachexia.

Signs

  • Look for red-flag symptoms in advanced disease:
    • General malaise
    • Bone pain (due to metastasis)
    • Anorexia
    • Weight loss
    • Obstructive nephropathy
    • Paralysis due to cord compression (secondary to metastasis)
  • Distended bladder due to overflow obstruction
  • DRE examination may reveal a hard, irregular prostate gland. Indication of possible prostate cancer are:
    • Asymmetry of the gland.
    • A nodule within one lobe.
    • Induration of part or all of the prostate.
    • Immobile - adhesion to surrounding tissue
    • Palpable seminal vesicles.

Differential diagnosis

  • Benign prostatic hyperplasia (BPH)
  • Any other cause of haematuria (e.g. UTI)
  • Prostatitis
  • Bladder tumour

Investigations

  • PSA ↑
  • Urinalysis: haematuria
  • Renal function test to exclude renal pathology
  • Trans-Rectal Ultrasound guided (TRUS) biopsy
  • Transperineal template biopsy: if TRUS negative/ inconclusive but high suspicion
  • MRI for staging
  • Isotope bone scan for bone mets

Grading system

  • Spread and staging by TNM scoring
  • Aggressiveness assessed Gleason score
    • Two areas of tumour specimen analysed for tumour differentiation: Well differentiated (scores 1) → Moderately differentiated → Poorly differentiated (scores 5)
    • The worse score from added up to give 2-10
    • 2-4= Indolent, 5-7= Intermediate, 8-10= Aggressive

Prognostic factors

Helps to determine between ‘watchful waiting’ vs aggressive treatment:

  • Pre-treatment PSA level
  • TNM staging
  • Tumour grading- Gleason score

Risk stratification (NICE 2014):

Urology MDT should risk stratify localised disease (T1-T2) as follows:

  • Low risk: PSA <10 and Gleason ≤6 and Stage T1 -T2a
  • Intermediate risk: PSA 10-20 or Gleason 7 or T2b
  • High risk: PSA >20 or Gleason 8-10 or ≥T2c

Management

Overview

A flowchart diagramme of the management of prostate cancer according to the UK NICE guideline

Management of Prostate cancer according to the UK NICE guideline

Conservative

  • Watch and wait
  • Indicated in elderly, multiple co-morbidities, low Gleason score with localised disease (harm from treatment > harm from cancer)

    Surgical management

  • Radical prostatectomy (open or laparoscopic)
    • Generally recommended if life expectancy >10 years (usually offered to patients <70yrs)
    • Robotic surgery
    • SE: Erectile dysfunction (40-30%), Incontinence

      Medical management

  • Active surveillance
    • Aimed at keeping patient within ‘window of curability’
    • Part of curative strategy
    • Delays radical treatment
  • Finasteride
    • Inhibitor of 5 alpha-reductase, an enzyme which metabolises testosterone into dihydrotestosterone. Used for LUTS
    • SE: impotence, low libido, ejaculation disorders, gynaecomastia
  • Radiotherapy
    • External beam radiotherapy – along with surgery, this can be curative. More suitable in elderly but many younger and generally fit patient may chose it as an alternative to surgery. Adverse effects: proctitis, and rectal cancer
    • Brachytherapy – radioactive ‘seeds’ are planted in the prostate by TRUS (Systemic SEs reduced) There are two types: Temporary high dose seeds (for advanced cancer) and Permanent low dose seeds (for early cancer)
  • Androgen suppression
    • Main treatment for metastatic disease
    • Used intermittently in localised or locally advanced disease (to delay refractory disease)
    • Response takes 24-36 months to develop but refractory disease eventually occur.
    • Synthetic GnRH agonist e.g. Goserelin, Degarelix– these stop the release of lutenising hormone, and thus the production of testosterone. It first simulate and then inhibit pituitary gonadotrophin → so patient may develop flare-up → give caution → Use anti-androgen in adjunct in susceptible pts
      • SEs: Hot flushes, Sexual dysfunction, Osteoporesis, Gynaecomastia, fatigue
    • Anti-androgen drugs: Cyproterone Acetate
    • Castration – unacceptable for many
Bladder Tumour
Testicular cancer