Prostate Cancer

Background

  • Most commonly diagnosed male cancer (excluding skin) in the UK
  • More common in older men- mean age ~72
  • Carries significant mortality (71% 5 year survival- 4th most common cause of death in men)

Aetiology

  • Hormonal factors
    • Like BPH, testosterone and dihydrotestosterone stimulate growth of the prostate and prostate cancers
  • Genes
    • There are a few genes that have been specifically associated with hereditary forms of prostate cancer e.g. PCAP and HPC1
  • Age
    • Largest risk factor- up to 67% of men >90 will have prostate cancer
  • Race
    • Prostate cancer is more common in Black and Caucasian patients compared to Asian populations (possible dietary factor e.g. oestrogens naturally found in food; or vit D)

Pathophysiology

  • The majority of prostate cancers are adenocarcinomas (>95%)
    • most arise in the peripheral zone (75%) and can be palpated as hard nodules.  The remainder mostly arise in the transition zone (20%)
    • Most cases have multifocal disease i.e. there are several distinct cancer lesions in the prostate (mean ~7)
  • Prostate cancer invades locally through the prostate capsule and into the surrounding tissues (locally advanced disease)
    • This often occurs along the autonomic nerves that innervate the prostate (i.e. perineural spread)
  • Prostate cancer can also metastasise, although the mechanism  behind this is poorly understood.  The most common site of spread is bone (particularly the axial skeleton)- and cause sclerotic lesions.
  • Genetic changes frequently occur in prostate cancer.  Common genetic changes are hypermethylation of GSTP1 (detoxifying enzyme); rearrangement of Ch21 with fusion of androgen dependent protease TMPR552 and transcription factors (which then become androgen-dependent); PTEN is also frequently mutated

Grading Prostate Cancer – Gleason Score

Gleason grade Lower grades are associated with...
Gleason grade Lower grades are associated with small, closely packed glands. Cells spread out and lose glandular architecture as grade increases. Gleason score is calculated from grade as described in the text. (Photo credit: Wikipedia)
  • The Gleason score is an important prognostic indicator in prostate cancer
  • It is calculated by adding the scores of the two most ‘common’ appearances within a biopsy- so the best score is 2 and worst is 10
      • Between 2-4 is well-differentiated; 5-7 is moderately differentiated and 8-10 is poorly differentiated
      • NB it can be useful to know the individual scores because if the predominant grade is worse, the prognosis could be also (e.g. 3+5 is better than 5+3).  The Gleason score can also be affected by treatments for prostate cancer, BPH and other androgen treatments and so should be interpreted with caution.
    • Prostate cancer is also staged using the TNM staging system

Presentation

  • History
    • Localised prostate cancer
      • Asymptomatic (abnormal PSA/DRE)
      • LUTS (in most cases due to co-existent BPH) & erectile dysfunction
      • Haematospermia/haematuria/dysuria (probably due to coexistent BPH/prostatitis)
    • Locally advanced prostate cancer
      • Asymptomatic
      • As above but may also have symptoms of ureteric obstruction (i.e. a degree of renal failure)
    • Metastatic disease
      • As above (including asymptomatic)
      • Bone pain (particularly back/shoulder pain); pathological fracture
      • Peripheral oedema/leg swelling due to lymphatic spread
      • Anorexia, weight loss
      • Neurological symptoms of lower limbs (spinal cord compression)
      • Anaemia
      • Dyspnoea, jaundice, bleeding tendency
  • Examination (DRE)
    • Most prostate cancer should be palpable on DRE
      • Hard, nodular, craggy, enlarged (cf soft, smooth and uniform)

Investigations

  • PSA (Prostate specific antigen)

PSA testing should be offered to:

Men older than 50 who request a PSA test

Men with unexplained symptoms that could be caused by locally advanced or metastatic prostate cancer

Men with LUTS that could be caused by BPH or by prostate cancer

    • Used in combination with DRE (and Gleason score once done) to predict likelihood of prostate cancer (and the pathological stage)
      • If DRE is abnormal and PSA >4, there is a 45% chance of diagnosis, which rises to >75% if PSA >10.
    • PSA tends to increase with advancing stage and tumour volume
      • i.e. if the PSA falls without any treatment, this is unlikely to be cancer
    • PSA is often a useful marker of disease progression/response to treatment
  • Transrectal ultrasound of prostate (TRUSP) usually with biopsy
    • Several core samples are taken for grading
  • Imaging (CT; PET CT and MRI)
    • In order to stage prostate cancer accurately, imaging is required
    • Bone PET scanning may be used if bone abnormalities/symptoms are detected after initial CT

Management

prostate ca risk

  • Men with low-risk localised prostate cancer should be offered active surveillance
    • Any patient with a change in PSA or symptoms should be offered radical treatment
    • Active surveillance will involve regular PSA and follow up (usually 6 months-1 year, but this will depend on the individual case)
  • Whilst active surveillance is also an option for intermediate risk disease, these patients, and those with high risk localised disease should be offered radical prostatectomy or radical radiotherapy
    • Hormonal treatment is recommended for minimum of 2 years in men receiving radical radiotherapy who have a Gleason score >7
  • For men with locally advanced prostate cancer
    • Radical radiotherapy
    • Hormone therapy should be given to all men treated with radical radiotherapy for 3-6 months (2 years if gleason >7)
  • Metastatic disease
    • Hormone therapy
    • Palliative care

Hormone therapy

  • Luteinising hormone releasing hormone (LHRH) and gonadotrophin releasing hormone (GnRH) analogues (goserelin and degarelix, respectively)
    • Effectively shut-down LH release in response to LHRH overload.
    • However, in the first 4-6 weeks, there will be an initial spike in LH production and thus testosterone production (in the prostate and testes) which can stimulate tumour growth (both in the prostate and metastases)
      • Anti-androgens should be given in conjunction to prevent this (e.g. bicalutamide)

 

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