1. Investigation and Management of Prostate Cancer
Mr C Dawson MS FRCS
Consultant Urologist
Edith Cavell Hospital, Peterborough

2. Investigation and Management of Prostate Cancer
How Prostate Cancer Presents
Examination of the Patient
Investigations, including PSA
Screening for Prostate Cancer
The Staging of Prostate Cancer
The Management of Prostate Cancer
Disease confined to the Prostate
Locally Advanced Disease
Metastatic Disease
Complications of Prostate Cancer
Palliative Care

3. How Prostate Cancer Presents
Disease confined to the prostate
There are no SPECIFIC symptoms of early stage prostate cancer
The symptoms are therefore the same as those of BPH
Hesitance
Poor / intermittent urinary flow
Terminal Dribbling
Nocturia / Frequency

4. How Prostate Cancer Presents
Locally Advanced Prostate Cancer
Cancer may invade the trigone and ureters causing ureteric obstruction
Bleeding
Pelvic Pain
Worsening of voiding symptoms

5. How Prostate Cancer Presents
Metastatic Prostate Cancer
Pain from bone metastases
Spinal cord compression
Pathological fractures
Poor general health / malaise

6. Examination of the Patient
General Examination
?Anaemic
Abdominal distension
?Palpable bladder
DRE (Digital rectal examination) of the Prostate

7. Investigation Haematological
FBC, Creatinine, LFTs
PSA
Consider need for Transrectal Ultrasound and biopsy of the Prostate (TRUS and biopsy)
Isotope bone scan – not indicated in asymptomatic patient with PSA <10ng/ml
CT / MRI

8. The Role of PSA
Single-chain glycoprotein of 240 amino acid residues and 4 carbohydrate side chains
Physiologic function is lysis of the seminal coagulum
Has a half-life of 2.2 days
Prostate specific, but not-cancer specific
Should not be used indiscriminately

9. Prostate Specific Antigen
In addition to Prostate cancer, an elevated level may be found with
Increasing age
Acute urinary retention and Catheterisation
TURP
Prostatitis
Prostate biopsy
BPH
Ejaculation
but NOT rectal examination

10. The Problem with PSA Men with Prostate cancer may have a normal PSA
Men with BPH or other benign conditions may have a raised PSA
No longer thought to be prostate-specific
What to do with men with PSA in the range 4-10 ng/ml?

11. Refinements in the use of PSA
Refinements theoretically most useful when PSA between 4-10 ng/ml
Below 4ng/ml prevalence of CAP ~ 1.4%, above 10ng/ml prevalence rises to 53.3%
PSA Density
PSA Velocity
Age-Specific PSA
Free vs. total PSA

12. Age Specific PSA Ranges
Determined from evaluation of PSA values and prostate volumes according to age
Age specific ranges make PSA a more sensitive marker for men <60yrs, and more specific in men > 60 yrs

13. Age Specific Reference Ranges

14. Free versus Total PSA
The majority of PSA in serum is bound to alpha-1-antichymotrypsin (ACT)
The proportion of free to total PSA is significantly lower in CAP
Not yet understood why this ratio changes in CAP
May be a way of discriminating patients with BPH and those with CAP

15. Free versus Total PSA
Choice of ratio cut-off remains to be decided - balance between missing some cancers and dramatically reducing the number of biopsies
The Free to Total (F/T) PSA Ratio is perhaps best reserved for difficult diagnostic cases; for example men with a PSA between 4-10ng/ml, or those who have previously had a negative biopsy

16. Free versus Total PSA 0-10 56 For men with PSA 4-10ng / ml and
% free PSA Probability of cancer %
>25 8

17. Screening for Prostate cancer
The Case For:
In order to hope to cure a patient the disease must be diagnosed when it is organ confined
The incidence of prostate cancer is rising by 3% per year
Prostate cancer is now the second commonest cause of death in men in Northern Europe

18. Screening for Prostate cancer
The case against
Transrectal ultrasound and biopsy has a morbidity rate
Negative biopsies lead to significant patient anxiety
Correct protocol has not yet been defined
May detect only incurable disease, or small tumours that are clinically unimportant (but…)

19. Cancers that are PSA detected
have been shown to be clinically significant
are frequently poorly differentiated or spread widely throughout the prostate
when removed by radical surgery will often be upgraded or upstaged.

20. Current opinion about screening?
Remains divided
Support for screening for prostate cancer is growing among eminent urologists (admittedly, those with an interest in prostate cancer)

21. The Staging of Prostate Cancer
TNM System
Gleason score

22. TNM Staging of Prostate Cancer
T1 – Impalpable / Not visible on TRUS
T1a: <5% of TURP chips
T1b: >5% of TURP chips
T1c: Detected on Prostate biopsy
T2 – Palpable OR visible on TRUS, but confined to prostate
T2a: Tumour in one lobe
T2b: Tumour in both lobes
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T3 – Extends beyond the boundary of the prostate
T4 – Fixed to other organs (e.g. bladder)
M0/M1 – No Metastases / Metastases
Confined to Prostate
Locally advanced
Metastatic

23. Gleason Score
Pathologist looks at two most common histological patterns under microscope
Gives each a score from 1-5
1=Well differentiated ………. 5=Poorly differentiated
Gleason score expressed as “Gleason X+Y” (e.g. Gleason 4+3)
Total Gleason sum score can also be expressed (e.g. Gleason 7 if using above example)

24. Management of Prostate Cancer confined to prostate
Four options
Watchful waiting
Radical Prostatectomy
Radical Radiotherapy (including brachytherapy)
(Hormones – See Metastatic disease)

25. Watchful Waiting Based on the results of autopsy studies
Many men die with prostate cancer rather than from it
Usual Indications
Stage T1a disease and well/moderately differentiated tumours and life expectancy > 10 years
Stage T1b-T2b: Patients with life expectancy < 10 years and asymptomatic

26. Radical Prostatectomy
Surgical excision of whole of Prostate/Seminal vesicles
Relatively low morbidity procedure in most series
Patient discharged home in 5-7 days
Trial without catheter at approx 14 days

27. Complications of Radical Prostatectomy
Source: EAU Guidelines Folder

28. Management of Prostate Cancer - Radiotherapy
Radiation therapy may produce treatment results comparable to those achieved by Radical Prostatectomy
NO randomised studies comparing radical radiotherapy, radical prostatectomy, and watchful waiting have been performed
Similar local control rates, and 10 year disease-free survival rates to radical prostatectomy
Good “free from PSA failure” rates
Similar Complication rates to Radical Prostatectomy
Bowel symptoms common during treatment

29. Management of Prostate Cancer - Brachytherapy
Interstitial radiation therapy (brachytherapy) appears to be making a comeback
Involves implantation of permanent radioactive seeds into prostate
Complication rates far less than for external beam radiotherapy
Not suitable for patients with significant voiding symptoms

30. Choice of Therapy? Patient choice after:
Full counselling by surgeon and oncologist
All questions answered
Partin’s tables can be helpful

31. Partins Tables

32. The Management of Locally Advanced Prostate Cancer
Cancer outside of prostate (by definition) so radical prostatectomy will not be curative
External beam Radiotherapy is an option
Hormonal Therapy – Casodex (Bicalutamide) – may be helpful

33. Management of Metastatic Prostate Cancer
The mainstay of treatment of metastatic disease is Anti-androgens, LHRH agonist, or Orchidectomy
Maximal androgen blockade has not proved of benefit for the majority of patients
Intermittent androgen blockade may be of benefit for selected patients, but the long-term durability and advantages are not clear at present

34. Management of Metastatic Disease – Hormonal Therapy
Options
Antiandrogens (e.g. Cyproterone Acetate)
LHRH agonists (e.g. Zoladex, Prostap)
Subcapsular orchidectomy
Must ALWAYS start with an antiandrogen
Potential spinal cord compression
Pathological fracture
Assess clinical response
Patient may then opt to stay on CPA, or try Zoladex or Orchidectomy

35. Management of Metastatic Disease
Median duration of clinical / PSA response is 24 months
Eventually disease becomes hormone unresponsive

36. Complications of Prostate Cancer
Pathological Fracture
Prostate cancer may present de novo with pathological fracture
Can be anticipated in some cases
Pain on weight bearing may herald pathological fracture
Prophylactic pinning of bone may be required

37. Complications of Prostate Cancer
Spinal Cord Compression
May present de novo
Can present with numbness/paraesthesiae, “off legs”, “falls”, urinary difficulty
Prevention is better than cure – function once lost is rarely regained
Treatment
Admit for bed rest
high dose prednisone
Urgent MRI of Spine
Admission to radiotherapy centre for DXT
Start hormone therapy if patient NOT already on hormones

38. Palliation of advanced symptoms
Pain from bone metastases - radiotherapy / steroids
Pain from locally advanced disease - radiotherapy
Lymphoedema of leg / DVT from pelvic nodal disease - radiotherapy
Ureteric obstruction - radiotherapy +/- stent or nephrostomy
Voiding dysfunction - “channel” TURP
Blood transfusion for anaemia