Investigation and Management of Prostate Cancer

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 • For men with PSA 4-10ng / ml and % free PSAProbability of cancer % 0-10 56 10-15 28 15-20 20 20-25 16 >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. 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 _____________________________________ 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 TNM Staging of Prostate Cancer

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

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