investigation and management of prostate cancer mr c dawson ms frcs consultant urologist edith...
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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
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