Tutorial: Prostate Cancer

Question 1

Summarize the epidemiology of prostate cancer

Answer 1

• In the UK: highest incidence in cancer
• 2nd commonest cause of cancer death (after lung)

Question 2

Which genetical components might be important in prostate cancer?

Answer 2

Not known yet but often

• PTEN defect (TSG)
• also something known in BRCA2 (TSG–> involved in DA repair)

Question 3

What are the symptoms of prostate cancer?

Answer 3

Prostatic hyperplasia

• polyuira
• problems with urination
• RArer
  
  • lower back pain
  • blood in urine
  • in metastisis: bone pain

Question 4

Which organs does prostate cancer spread to?

Answer 4

Can metastasis or directly spread to

• bladder
• seminal vesicles
• metastisis: lymph and bone

Question 5

What is PSA physiologically?

Answer 5

Polypeptide, which is part of the seminal fluid

(not found in blood)

Question 6

What does an increase in PSA show?

Answer 6

PSA: should only be found in seminal fluid

• shows defect in basement membrane in the prostate but only shows some sort of prostate irritation. It could be
  
  • inflammation
  • rigous cycling
  • benign hyperplasia
  • prostate cancer

Question 7

What are further diagnostic test after someone presenting with a raised PSA and symptoms of prostate cancer?

Answer 7

• Digital rectal exam
• MRI scan
• Biopsy + Grading (Gleason scoring) –> often not accurate

Question 8

What are the liminations of the GLeason scoring in prostate cancer?

Answer 8

• often under or overestimates the cancer
• not accurate, might miss things
• Even if grading is correct:
  
  • no way of predicting weather is is slow growing (most men) or fast growing + metastatic (rarer)

Question 9

Whay is PSA testing not used as a screening test for prostate cancer?

Answer 9

Because its sensitivity + spcificity is too low and would be

1. too expensive
2. make little /no difference
3. too many unnecessary tests and anxiety

Question 10

Which general treatment options for the treatment of prostate cancer are avialable

Answer 10

1. “Active observation”, expecially in older patients with low grade
2. Surgery (depending on age) + cancer only in prostate
   
   • side effects of incontinence and impotence
3. Radiotherapy ( if tumor is only in prostate)
4. Hormone Therapy

Question 11

Summarise the rationale behind Hormone Therapy in Prostate cancer

Answer 11

Normally: Prostatic growht is promoted by the pituitary

1. GnRH analogue: overstimmlation of pituitary leading to desensitiation of pituitary LHRH receptors –> don’t respond to it anymore –> No LH+ FSH secretion –> no testicular androgens
2. • Anti-androgen (for adrenal testosterone)

Question 12

What are the side effects of hormone therapy in prostate cancer?

Answer 12

• osteoporosis
• loss of libido
• anaemia
• muscle atrophy
• memory loss
• gynaecomastia

Question 13

Why can prostate cancers still grow despite haveing no ciruculating andrognes?

Answer 13

1. Often: become “androgen independence”
   
   • become very sensitive to androgen, possible via
     
     • co-activation (overexpression of proteins that are required for androgen receptor signaling)
     • overexpression of androgen receptor
     • amplification of low levels of androgens
     • decrease of co-repressors
     • mutation of androgen receptor becoming sensitive to other steroids (e.g. oestrogen, anti-andrognes)
   • ligant-indipendant activvation of androgen receptor
   • bypass of androgen receptor pathway (PTEN loss)

Question 14

What are the drug names for the drugs used in prostate cancer treatment?

Answer 14

1. LHRH analogut: Leuprorelin
2. flutamide= anti-androgen