Investigation and Management of Prostate Cancer

Mr C Dawson MS FRCSConsultant Urologist

Edith Cavell Hospital, Peterborough

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

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

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

How Prostate Cancer Presents

• Metastatic Prostate Cancer– Pain from bone metastases– Spinal cord compression– Pathological fractures– Poor general health / malaise

Examination of the Patient

• General Examination– ?Anaemic– Abdominal distension– ?Palpable bladder– DRE (Digital rectal examination) of the Prostate

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

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

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

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?

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

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

Age Specific Reference Ranges

Age PSA40 - 49 <= 2.550 - 59 <= 3.560 - 69 <= 4.570 - 79 <= 6.5

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

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

Free versus Total PSA

• For men with PSA 4-10ng / ml and

% free PSA Probability of cancer %

0-10 56

10-15 28

15-20 20

20-25 16

>25 8

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

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…)

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.

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)

The Staging of Prostate Cancer

• TNM System• Gleason score

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

_____________________________________• 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

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)

Management of Prostate Cancer confined to prostate

• Four options– Watchful waiting– Radical Prostatectomy– Radical Radiotherapy (including brachytherapy)– (Hormones – See Metastatic disease)

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

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

Complications of Radical Prostatectomy

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

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

Choice of Therapy?

• Patient choice after:– Full counselling by surgeon and oncologist– All questions answered

• Partin’s tables can be helpful

Partins Tables

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

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

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

Management of Metastatic Disease

• Median duration of clinical / PSA response is 24 months

• Eventually disease becomes hormone unresponsive

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

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

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