Investigation and Management of Prostate Cancer Mr C Dawson MS FRCS Consultant 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

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 0-10 56 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 Source: EAU Guidelines Folder

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