Prostate cancer

Question 1

Epidemiology of prostate cancer

Answer 1

• Commonest urological malignancy and male deaths
• commonest cause of male cancer death - 3% of all men

Question 2

Risk factors for prostate cancer

Answer 2

• Genetic – HPC1 gene
• Hormones (increased dihydrosterterone, or increased 5 alpha reductase)
• Obesity
• Environmental – work environment
• Diet – Vitamin D and E protective
• Age > 65
• Racial

Question 3

Symptoms of prostate cancer

Answer 3

• often none until advanced
• diffuclty voiding -catheter required
• prostate gland becomes hard
• pain
• spinal cord compression- causing lower limb weakness, due to metastatic disease in the Lumbar spine

Question 4

Signs of prostate cancer

Answer 4

• Local- confined to the prostate (66%)
  
  • Often asymptomatic
  • Can have lower urinary tract symptoms- haematuria or UTI
  • Urinary retention (anuria, uraemia)
• Locally advanced- into rectal/pelvic wall or lymph nodes (27%)
  
  • Lymphoedema
  • Metastastic (7%)
  • Weight loss
  • Cachexia
  • Bone pain- most common mestasases
  • Renal failure-ureteric obstruction
• *Raised PSA level- on suspicion or screening*

Question 5

Diagnosis and screening of prostate cancer

Answer 5

• Digital Rectal Examination
• Prostate-specific antigen–> require counselling as the test following this is TRUS:
• Trans-Recal U/S biopsy- risk of complications–>retention, haematuria, sepsis (1-2% of severe sepsis)

Question 6

Pathology of prostate cancers

Answer 6

• Majority are adenocarcinoma
• 2/3 arises in the peripheral zone of the prostate (back portion, felt on DRE)

Question 7

How are renal cancers graded?

Answer 7

Gleason grading

Graded using histological Gleason Grading cell pattern, a combined sum of numbers 1-5

• *Pattern 1 -** small, uniform
• *Pattern 2 -** More stoma between glasnds
• *Pattern 3** - Distinctinly infiltrative margins
• *Pattern 4** - Irregular masses of neoplastic glands
• *Pattern 5** - Occasional gland formation

The higher the Gleason score, the more likely it is that the cancer will grow and spread rapidly. Pathologists often identify the two most common patterns of cells in the tissue, assign a Gleason grade to each, and add the two grades. The result is a number between two and 10

Question 8

Staging of prostate cancer

Answer 8

TMN

• Local - MRI/CT
• Distant - bone scan

Question 9

Prostate specific antigen

Answer 9

• Serine protease that is secreted into seminal fluid
• Role is to liquefy seminal coagulation, efficiently hydrolyses semenogelins - to allow for sperm release. Measured in serum, as a small proportion leaks into circulation
• Tissue specific not Tumour specific – poor diagnostic test.
• PSA- affected by:
  
  • Age- rises with age
  • Depends on prostate size (consider benign prostatic hypertrophy)
  • Can be increased by UTI (sharp rise)
  • Chronic prostatitis
  • Instrumentation can increase it (catheter etc.)
• PSA>4mg/ml requires investigation

Question 10

PSA advantages and disadvantages

Answer 10

Advantages

• More acceptable than DRE
• Detects cancers
• Predicable value
• Reassurance if tests are normal

Disadvantages

• Not specific for prostate cancer
• Unnecessary patient stress
• May not identify men with confined organ disease

Question 11

Treatment for prostate cancer

Answer 11

1. watchful waiting
2. active surveillance
3. radical - surgery v DXT v Brachytherapy
4. palliative - DXT, radium or stontium
5. Hormone treatment - GnRH agaonist or antagonists

Question 12

Metastatic complications of prostate cancer

Answer 12

• Spinal cord compression: Urological emergency - Severe pain, off legs. Retention, Constipation.
  
  • Urgent MRI
  • Refer for radiotherapy/decompression surgery
  • LHRH agonist
• Ureteric obstruction: Anorexia, Weight loss, Raised creatinine
  
  • To nephrostomize or not and then to stent or not
  • Temporary measure will not improve cancer progression

Question 13

Hypothalamic-pituitary-testicular axis

Answer 13

• The hypothalamus releases CRH & GnRH
• Act on the pituitary to release Luteinising hormone and follicle stimulating hormone
• These act on the testes to create testosteroneàprostate and also act on the Adrenal glands
• There is short loop and long loop negative feedback from all of this to reduce the hypothalamic activity
• Adrenocorticotrophic hormone (ACTH) is released from the pituitary gland after stimulation by corticotrophin-releasing hormone (CRH) which is secreted from the hypothalamus.12 ACTH regulates secretion of adrenal androgens, some of which are converted to testosterone.
• LHRH agonists-stimulate the testes at first, but due to negative feedback lead to the reduction in the testes and reduced testosterone
• Antagonist-block the receptor, inhibit testosterone straight away-given for patients with spinal cord compression