Cancer - Prostate

Question 1

What is the mortality of CaP? Main risk factors?

Answer 1

• Most common cancer in men and 2^nd most important cause of mortality
• Risk factors:
  
  • Age
  • Family history: 4x increased risk if one degree relative diagnosed before age 60
  • BRCA2 mutation: 5-7x increased risk (don’t tend to respond to radiotherapy)
  • Other risk factors: being black, being tall and use of anabolic steroids

Question 2

What is the presentation of CaP?

Answer 2

• Presentation is similar to BPH (or can be asymptomatic) but can also include haematuria, erectile dysfunction and general signs of cancer and metastasis (e.g. weight loss, fatigue and bone pain)

Question 3

What Investigations should you do when suspecting CaP?

Answer 3

• PSA
• DRE
• Biopsy
• Imaging: MRI or PET

Question 4

What is PSA? When should it be used? Name causes of raised PSA?

Answer 4

• Protein that liquefies semen
• Traditionally done prior to DRE to avoid stimulating release of PSA
• Not very sensitive or specific (positive and negative results are unreliable)
• Most useful in monitoring the progression of the disease and success of treatment
• Common causes of raised PSA: prostatitis, UTI, prostate cancer, BPH, acute urinary retention

Question 5

What imaging should you perform as part of Ix for CaP?

Answer 5

• MRI prostate pelvis: increasingly performed pre-biopsy (informs biopsy technique or can be biopsy sparing
• If MRI done after biopsy: must wait 4-6 weeks for inflammation to settle down
• If suspected advanced disease or patient has bone pain: PET scan – will show osteoblastic/sclerotic lesions

Question 6

What types of biopsy can you do?

Answer 6

• The definitive method for diagnosing prostate cancer
• Still not particularly sensitive because cancers may be located in areas not biopsied
• Multiple needle biopsies are taken to minimize risk of missing the cancer
• Options:
  
  • Transrectal Ultrasound-Guided Biopsy (TRUS)
    
    • Ultrasound inserted into rectum and a needle biopsy taken through rectal wall into prostate under US guidance – local anaesthetic used
    • Usually around 10 biopsies are taken to try and pick up the cancer
  • Transperineal
    
    • This method allow more biopsies to be taken (around 35)
    • This has a higher sensitivity than TRUS
    • It takes longer than TRUS and requires general anaesthetic

Question 7

Mx: what factors will influence the treatment of a patient with CaP?

Answer 7

• Age and functional status
• PSA
• Biopsies: Gleason grade and extent
• MRI (pelvis) and bone scan: N-stage and M-stage
• DRE: T stage
  
  • 1-2 localised
  • 3 locally-advanced
  • 4 Advanced

Question 8

Describe the Gleason Grading system

Answer 8

• Specific to prostate cancer – gives score out of 10 based on the differentiation of the 2 biggest regions of tumour. Scale 0-5, 5 being very poorly differentiated.
• Helps to determine what treatment is most appropriate
  
  • 6 or less: cancer likely to develop slowly
  • 7: intermediate risk for aggressive cancer 3+4 is better than 4+3 b/c means the largest area has a better (lower score on the scale)
  • 8 or higher: cancers likely to spread more rapidly – poorly differentiated and high grade
• The higher the grade (especially in the first number) the worse the prognosis

Question 9

Describe the treatment options for localised CaP

Answer 9

Low risk:

• Active surveillance in low risk patients: annual DRE in clinic and PSA 2x/year

Moderate risk:

• Radical prostatectomy: PSA <20 and BMI <35, intermediate risk (1-2 nodes) – robotic approach is now gold standard
• Radiotherapy directed at the prostate
• Brachytherapy
  
  • Radioactive seeds implanted into the prostate
  • Deliver continuous, targeted radiotherapy to the prostate

Question 10

Describe possible complications of prostatectomy followed by radiotherapy

Answer 10

• Erectile dysfunction
• Urinary incontinence
• Radiation induced enteropathy (giving gastrointestinal symptoms like PR bleeding, pain, incontinence etc)
• Urethral strictures

Question 11

Describe the treatment options for patients with metastatic CaP

Answer 11

• If performance status is 0-1: can give upfront Docetaxel chemotherapy before starting hormonal treatment
• Hormonal treatment: prostate tissue grows in response to androgens like testosterone – blockage of androgens results in slowing or halting of prostate cancer growth
  
  • Side effects: hot flushes, sexual dysfunction, gynaecomastia, fatigue and osteoporosis
• Hormonal treatment options:
  
  • Bilateral orchidectomy is the gold standard hormonal treatment
  • LHRH agonists cause chemical castration (e.g. goserelin) – more effective in systemic/metastatic disease than androgen receptor blockers
  • Androgen receptor blockers (e.g. bicalutamide) as add on to block initial surge of androgens

Question 12

What treatment can we provide for palliative patients with bone pain?

Answer 12

• Single dose radiotherapy: decreases opioid use and relieve mets bone pain
• Bisphosphonates: Zolendronic acid

Question 13

What is the problem with a PSA based screening programme?

Answer 13

• PSA can be raised or normal with or without CaP – PSA levels do not correlate with DRE findings
• PSA check can lead to uncertainty and anxiety
• PSA based screening leads to over-diagnosis (indolent/insignificant CaP) and significant loss of QALYs owing to post Dx long-term effects
• Not cost-effective - 1 CaP death averted per 781 men invited

Question 14

Explain lead and length time bias

Answer 14

• Lead time bias: appearance that early diagnosis of a disease prolong survival with the disease
• Length time bias: overestimation of survival duration due to relative excess of cases detected that are asymptomatically slow growing progressing, while fast progressing cases are detected after giving symptoms