Prostate cancer

Why is there currently a problem?

Prostate Cancer Advisory Group April 2007

• ‘Prostate cancer patients in the NHS have historically reported a worse experience than patients with other cancers. The gap in reported experience between prostate cancer and other cancers has actually widened between 1999 and 2004. Not all men currently get access to high standards of advice and support on treatment options’

Background

• What does the prostate gland do?• What diseases affect the prostate?• What is the incidence and prevalence of prostate cancer?• What is the workload?• How do we grade prostate cancers?• What disease scoring systems are used?• What are the clinical features of prostate cancers?• Are they all the same?• What are the known risk factors?• Are there any preventive treatments?

What does the prostate gland do?

• Makes, stores and secretes an enzyme-rich fluid that makes up about 1/3 of the ejaculate volume (the rest is produced by the seminal glands)

• The main role is to liquefy semen and protect sperm during fertilisation

• Smooth muscle around the prostate helps to expel semen during ejaculation

• The function of the prostate is regulated by androgens (mainly testosterone)

What diseases affect the prostate?

Diseases of the prostatewww.cancerscreening.nhs.uk/prostate

• Prostate cancer– Malignant growth of prostate cells, localised and may spread– Nearly all prostate cancers are adenocarcinomas, mainly occurring

in the peripheral zone of the prostate gland– Rare in men < 50, and is more common with increasing age

• Benign prostatic hyperplasia– Non-malignant increase in size of the prostate with age– Rare in men under 50

• Prostatitis– Inflammation of the prostate– Can occur in men of any age

The early symptoms of prostate diseases are very similar

What is the incidence and prevalence of prostate cancer?

Prostate cancer: Incidence and prevalencewww.info.cancerresearchuk.org

• Most common cancer in men in UK• In 2005 >34000 men in the UK were newly diagnosed• ¼ of all newly diagnosed cancers in men• Accounts for 12% of male deaths from cancer in the UK and is

the 2nd most common cause of cancer death in men after lung cancer

• Lifetime risk is 1 in 14• ½ of men in their 50’s have histological evidence of prostate

cancer, which rises to 80% by 80 years, but only 1 in 26 men (3.8%) die from the disease

• Men are more likely to die with it than from it

What is the workload?

What is the workload?NICE 2002

• A GP with a list size of 2000 is likely to see 1-2 new patients with urological cancer each year

• A DHG serving 200000 people deals with 70 men with prostate cancer each year out of 150 urological cancers

How do we grade prostate cancers?

TNM stages of prostate cancerwww.cancerhelp.org.uk

• Tumour

– T1 – Tumour too small to be seen on scans or be felt on examination

– T2 – Tumour completely inside the prostate gland (palpable)

– T3 – Tumour has broken through the capsule of the prostate gland

– T4 – Tumour has spread to other body organs nearby such as rectum or bladder

TNM stages of prostate cancerwww.cancerhelp.org.uk

• Lymph nodes– N0 – No cancer cells found in any lymph nodes– N1 – one +ve lymph node smaller than 2cm across– N2 – more than one +ve lymph node. Or one that is

between 2-5cm across– N3 – Any +ve lymph node that is >5cm across

• Metastases– M0 – No cancer spread outside the pelvis– M1 – Cancer has spread outside the pelvis

What disease scoring systems are used?

Gleason scoreEUA guidelines 2007

• Most commonly used system

• Total score ranges from 2 (least aggressive) to 10 (most aggressive)

– The sum of the 2 most common patterns (grades 1-5) of tumour growth found in the biopsy specimen

• The Gleason histological score correlates well with prognosis in localised prostate cancer, but there is considerable observer variation

What are the clinical features of prostate cancers?

Clinical features of prostate cancerwww.cancerscreening.nhs.uk/prostate/prostate-booklet-text.pdf

• Prostate cancers (unlike BPH) tend to develop in the outer part of the prostate gland

• Unusual for early cancers to cause any symptoms

• Locally advanced prostate cancers that have extended outside the capsule are also frequently without symptoms

• If the tumour is large enough, it can cause lower urinary tract symptoms (LUTS) eg frequency, urgency, hesitancy, leaking, but by the time this happens the cancer will usually have reached an advanced stage

• LUTS are similar to those of BPH. Most men with LUTS will not have prostate cancer

• Often the first sign of prostate cancer is evidence of metastases (frequently in bone, causing bone pain) – About 20–30% of patients in

the UK present with metastatic disease

Are they all the same?

Prostate cancers vary in their natural histories

• Prostate cancer is biologically heterogeneous

• Some grow very slowly and never cause symptoms, others grow fast and metastasise quickly, other types grow at a modest pace

What are the known risk factors?

Risk factors for prostate cancerwww.info.cancerresearchuk.org

• Age– Increases with age

• Ethnicity– Highest rates in African-American men– Lowest rates in Asians

• Family history– 2-3x higher for men with FH in 1st degree relative,

particularly is a brother, or were affected when young• Diet– Associated with Western diet

Are there any preventive treatments?

Finasteride: Preventative therapy?Thompson IM, et al. N Engl J Med 2003; 349: 215-24

• Increases sexual side effects but decreases urinary symptoms

• May prevent or delays the appearance of prostate cancer but this possible benefit and reduced risk of urinary problems must be weighed against sexual side effects

• There is no evidence that preventative therapy increases survival

• Not licensed in the UK for the prevention or treatment of prostate cancer

Screening and diagnosis

• How do you detect prostate cancer?• What is the role of PSA detection?• Can we use digital rectal examination to improve prostate

cancer detection?• What are the referral guidelines for specialist investigations?

How do you detect prostate cancer?

Detection of prostate cancerNICE 2002

• Prostate cancer can be detected by:– Digital rectal examination (DRE)– Prostate specific antigen (PSA) testing– Trans-rectal ultrasound (TRUS) guided biopsy– Pathological examination of tissue samples removed

following TURP– CT/MRI scans provide information on staging and spread

– Before referral men should be offered DRE and PSA testing as set out in ‘Referral guidelines for suspected cancer’ CG27 - NICE CG 58, 2008

What is the role of PSA detection?

Prostate specific antigen (PSA)

• PSA is produced by prostatic epithelium and is present in seminal fluid, urine and serum. It is involved in the liquefaction of seminal coagulum formed at ejaculation

• With cancer the epithelial cells are disorganised and the barrier between the prostate and blood vessels is disrupted. More PSA leaks into the blood vessels as a result

Prostate specific antigen (PSA)NICE 2002. Improving outcomes in urological cancers

• Men with cancer tend to have higher levels in their blood (up to 30% have normal levels)

• There is no level below which a man does not have prostate cancer, nor is there a level that is agreed as diagnostic

• Levels tend to increase naturally with age• Levels tend to increase with other conditions eg BPH, urinary

infection• Different assay systems can produce different results and

levels can vary in response to– Exercise– Sexual activity– Clinical investigation– Other forms of treatment

Can we use digital rectal examination to improve prostate cancer detection?

Digital rectal examination NICE 2002. Improving outcomes in urological cancers. The

Manual. 2002. www.NICE.org.uk

• The cancer may not produce symptoms until it is at an advanced stage, but early cancer can be detected by DRE, which is used to investigate LUTS

• A positive test cannot be used for diagnosis but does indicate a need for further investigations &/or referral

What are the referral guidelines for specialist investigations?

Referral guidelines for suspected cancer: Prostate cancer

NICE CG 27. June 2005• A DRE and PSA (after counselling) are recommended for a

patient with any of the following symptoms:

– Inflammatory or obstructive urinary tract symptoms– Erectile dysfunction– Haematuria– Lower back pain– Bone pain– Weight loss, especially in the elderly

• Exclude UTI before PSA testing. Postpone a PSA for at least 1 month after treatment for a proven UTI

Referral guidelines for suspected cancer NICE CG 27. June 2005

• In an asymptomatic male with a borderline PSA, repeat test after 1-3 months. If PSA is rising, refer patient urgently

• Refer a patient with symptoms and signs or a urological cancer to a specialist team

• Urgent referral:– Patient with a hard irregular prostate. Measure PSA and

send with referral (not urgent if prostate is simply enlarged and PSA is in the age-referenced range)

– Patients with a normal prostate but rising / raised age-specific PSA with or without LUTS

– Patients with symptoms and high PSA levels

What are the age specific cut offs for PSA measurements and referral?

Age-specific cut offs for PSA measurements and referralNICE CG 27, June 2005

Age rangeAge range PSA measurementPSA measurement

50-5950-59 ≥ ≥ 3.0ng/ml3.0ng/ml

60-6960-69 ≥ ≥ 4.0ng/ml4.0ng/ml

≥ ≥ 7070 ≥ ≥ 5.0ng/ml5.0ng/ml

>80>80 No age specific reference rangesNo age specific reference ranges

Nearly all men have over 80 have at least a focus or cancer in the prostate. Nearly all men have over 80 have at least a focus or cancer in the prostate. Only need to be diagnosed if likely to need palliative treatmentOnly need to be diagnosed if likely to need palliative treatment

What ten principles should govern a screening programme?

Ten principles which should govern a national screening programme

www.cancerscreening.nhs.uk/prostate/index.htlm

• The condition is an important health problem• Its natural history is well understood• It is recognisable at an early stage• Treatment is better at an early stage• A suitable test exists• An acceptable test exists• Adequate facilities exist to cope with abnormalities detected• Screening is done at repeated intervals when the onset in

insidious• The chance of harm is less than the chance of benefit• The cost is balanced against benefit

The Department of Health view

• There is often increased anxiety amongst men with risk factors. If these men present in primary care it is important that they receive the best available information to assist them in deciding whether or not to have a PSA test

• Until more evidence is available about screening active case finding of men with risk factors is not recommended

Prostate cancer risk management

• Although evidence does not yet support population screening there is considerable demand for the PSA test amongst men worried about the disease

• In response the Government has introduced a PSA Informed Choice Programme – Prostate Cancer Risk Management

• Key elements:– Provision of high quality information for those requesting

testing– Enables them to decide whether to have the test based on

available evidence about risks and benefits

Should you take the test?

Should you take the test?www.cancerscreening.nhs.uk/prostate/prostate-summary-

sheet.pdf

Benefits• May provide reassurance if

normal• May find cancer before

symptoms develop• May detect cancer at an early

stage when treatments could be beneficial

• If treatment is successful the consequences of more advanced cancer is avoided

Risks• It can miss cancer and provide

false reassurance• It may lead to unnecessary

anxiety and medical tests when no cancer is present

• It might detect slow growing cancer that may never cause any symptoms or shorten life span

• The main treatments have significant side effects and there is no certainty that Rx will be successful

What would happen to 1000 men aged 50-70 years having a PSA test?

• 900 are –ve and 7 later develop prostate cancer• 100 are +ve• 100 undergo biopsy• 74 are –ve and 7 later develop prostate cancer• 26 are +ve

• It is not known how many of these would have suffered any morbidity or mortality are a result of their cancer if it have been detected earlier

Detecting prostate cancer: BiopsyNICE CG58 2008

• Provide– Information– Support– Time to make decisions

• Discuss– Risks and benefits of biopsy– Individual risk factors– Estimated prostate size– DRE finding and PSA level– Comorbidities

Treatment and service issues

• What are the treatment options for prostate cancer?• What factors influence choice?• What clinical evidence is there for the effectiveness of current

treatment options?• What about harms of treatment?• What support should be offered to patients with prostate

cancer?• How can we improve standards of care for patients with

prostate cancer?

What are the treatment options for prostate cancer?

www.nice.org.uk/CG58

Localised

Watchful waitingActive surveillance

Radical prostatectomy

External beam radiotherapy

Brachytherapy

Localised advancedNeoadjuvant and concurrent LHRHa with radiotherapy

Adjuvant hormonal therapy with radiotherapy

Pelvic radiotherapy

High Intensity Ultrasound or CryotherapyOnly as part of a clinical trial

Metastatic

Orchidectomy or continuous LHRHa

Bicalutamide or androgen withdrawal

Intermittent androgen withdrawal

Hormone refractory

Docetaxel

Corticosteroids

Spinal MRI (spinal metastases)

Decompression of urinary tract (obstructive uropathy)

Palliative care

Managing side effects of treatment

Erectile dysfunction (PDE5 inhibitors first line)

Urinary incontinence – refer for possible artificial sphincter

Side effects of hormonal treatments

Hot flushes — progestogens

Gynaecomastia with bicalutamide — radiotherapy to breast buds (or tamoxifen if fails)

Painful bone metastases – strontium-89 or bisphosphonates

TREATMENTS

What factors influence choice?

Factors influencing the decision to treatwww.cancerbackup.org.uk

• Deciding on the best treatment is not always straightforward. The most important factors to consider are:– General health– Grade and stage of the cancer– Whether it has spread beyond the prostate– PSA level– Likely side effects of treatment– Views about the possible side effects and how much this

will be risked vs. Benefits in controlling the cancer– Age

Communication and supportNICE Clinical Guideline 58; 2008

• Health professionals should:– Support men and their partners or carers in making treatment decisions,

taking into account the effects on quality of life as well as survival– Inform men, their partners or carers about the effects of prostate cancer and

their treatment options on:• Their sexual function• Physical appearance• Continence• Other aspects of masculinity

– Offer sperm storage and access to specialist support services as appropriate eg• Erectile dysfunction• Urinary complications

Risk stratification criteria for men with localised prostate cancer

NICE Clinical Guideline 58; 2008

PSA (ng/ml)

Gleason score Clinical stage

Low risk < 10 and ≤ 6 and T1 – T2a

Intermediate risk 10-20 or 7 or T2b – T2c

High risk > 20 or 8-10 or T3 – T4

MDTs should assign a risk category to all men newly diagnosed with prostate cancer

What clinical evidence is there for the effectiveness of current treatment options?

Treatment options for localised prostate cancerNICE Clinical Guideline 58; 2008

Low risk Intermediate risk High risk

Watchful waiting □ □ □

Active surveillance ● □ ◊

Prostatectomy □ ● ●

Brachytherapy □ □ ◊

Conformal radiotherapy □ ● ●

Cryotherapy ◊ ◊ ◊

High intensity focused ultrasound

◊ ◊ ◊

● Preferred Rx□ Treatment option◊ Not recommended

Watchful waitingNICE Clinical Guideline 58; 2008

• Involves the conscious decision to avoid treatment unless symptoms of progressive disease develop– Older men– Those with significant comorbidity– Those unlikely to have significant cancer progression

during their lifespan

• Measure PSA once a year

• Routine DRE not recommended

Active surveillanceWilt T and Thompson IM, BMJ 2006; 333: 1102-1106

• Active plan to postpone intervention. Involves monitoring (reassessment of risk) at regular intervals with serial PSAs and repeat biopsy, with further treatment (curative or palliative) based on patient preference, symptoms and clinical findings

• Potential benefits– No immediate side effects– Low initial cost– Most (especially low to intermediate risk) do not need treatment and survive

at least 10 years

• Potential risks– Cancer not removed so could advance, become incurable and cause death– Quality of life could be painfully restricted– Other Rxs may be necessary, not effective, have side effects, patient may be

too worried to monitor cancer without Rx

Radical prostatectomyWilt T and Thompson IM, BMJ 2006; 333: 1102-1106

• Complete surgical removal of the prostate gland with seminal vesicles, ampulla of vas, and sometimes pelvic lymph nodes

• Potential benefits– May eliminate cancer

• Potential risks– Major surgery– May not eradicate cancer– Long term urinary incontinence– Urethral stricture– Bladder neck contracture– Bowel and erectile dysfunction

External beam radiotherapyWilt T and Thompson IM, BMJ 2006; 333: 1102-1106

• Multiple doses of radiation from an external source applied over several weeks. Conformal radiotherapy uses 3-D planning systems to maximise dose to prostate cancer and to spare normal tissue

• Potential benefits– May eliminate cancer– Generally well tolerated– Avoids operative risks

• Potential risks– Prostate not removed and eliminated– 5-8 weeks of outpatient Rx– Rx related death– Incontinence– Proctitis– Diarrhoea– Cystitis– Erectile dysfunction– Urethral stricture– Bladder neck contracture and bleeding– Contraindicated with IBD

BrachytherapyWilt T and Thompson IM, BMJ 2006; 333: 1102-1106

• Radioactive implants placed under anaesthesia using radiological guidance. Lower dose permanent implants typically used. External beam ‘boost’ radiotherapy or androgen deprivation sometimes recommended

• Potential benefits– May eliminate cancer– Generally well tolerated– Avoids operative risk– Single outpatient session

• Potential risks– Does not eradicate cancer– May not be effective for larger glands or more aggressive tumours– Urinary retention– Incontinence– Impotence– Cystitis or urethritis and proctitis– Contraindicated if previous TURP

Radical treatmentsNICE Clinical Guideline and Full Guideline 58; 2008

• Radical prostatectomy or radical radiotherapy should be offered to:– Men with intermediate-risk localised cancer– Men with high-risk localised cancer where there is a realistic prospect

of long-term disease control

• Brachytherapy not recommended for men with high-risk localised cancer

• Adjuvant hormonal therapy recommended for minimum of 2 years in men receiving radical radiotherapy for localised prostate cancer with a Gleason score ≥ 8

• PSA levels should be checked 6 weeks following treatment, at least every 6 months for 2 years and then at least once per year

Cryotherapy and HIFUWilt T and Thompson IM, BMJ 2006; 333: 1102-1106

Cryotherapy (cryoablation) High-intensity focused ultrasound (HIFU)

Destruction of cells through rapid freezing and thawing using transrectal guided placement of probes and injection of freezing and thawing gases

Destruction of cells through heat generated through absorption of ultrasound emitted from endorectal probe. A cooling balloon surrounding the probe protects the rectal mucosa

Potential benefits – May eliminate cancer; generally well tolerated; avoids operative risk; single outpatient session (general or regional/spinal anaesthesia

Potential risks – Does not remove prostate gland and may not eradicate cancer. More research needed – no long-term outcome data

Main side effects: Impotence (72-100%), Incontinence (1-19%), fistula (<1-2%)

Main side effects: Impotence (24-100%), UTI and stress incontinence (4-48%), fistula (0.7-3%)

High-intensity focused ultrasound and cryotherapyNICE CG and full guideline 58; 2008

• Insufficient evidence of clinical and cost-effectiveness in comparison with established interventions

• Not recommended for men with localised prostate cancer other than in the context of controlled clinical trials comparing their use with established interventions

Hormone therapy (androgen deprivation therapy)EAU Guidelines 2005; NICE TA101 2006;

Damber JE, Aus G. Lancet 2008;371:1710–1721

• Prostate cells are physiologically dependent on androgens (mainly testosterone) to stimulate growth, function and proliferation

• The testes are the source of 90–95% of androgens (5–10% from adrenal glands)

• If prostate cells are deprived of androgenic stimulation, they undergo apoptosis (programmed cell death)

• Any treatment that ultimately results in suppression of androgen activity is called androgen deprivation therapy (ADT)

• Can be achieved by suppressing secretion of the testicular androgens (castration, LHRH agonists), by inhibiting the action of circulating androgens (anti-androgens), or both (complete androgen blockade)

Methods used for androgen depletionNICE. Improving outcomes in urological cancers. 2002

Method Advantages DisadvantagesOrchidectomy Low cost in long term

No other treatment is more effective

IrreversibleUnacceptable to some menLoss of libidoSymptoms similar to female menopause

LHRH agonistseg gosereline

ReversibleProbably as effective asorchidectomy

Side effects similar to surgery but with a wider range of symptoms. Initial stimulation of testosterone can produce tumour ‘flare’

Anti-androgenseg biclutamide, flutamide, cyproterone

Can be used with LHRH agonists to reduce tumour flareCan be used alone in certain circumstancesSide effects may be less severe than LHRH agonists

Side effects similar to LHRH agonists. May be less effective than surgery or LHRH agonists when used alone. Common side effects include gynaecomastia and risk of liver failure

NICE recommendations for managing the complication of hormonal therapy

NICE Clinical Guideline and Full Guideline 58;2008

• Offer oral or synthetic progestogens for hot flushes. Offer oral therapy for 2 weeks and re-start when flushes recur, if effective

• Offer prophylactic radiotherapy to breast buds within the first 6 months of long-term (>6 months) treatment with bicalutamide

• Consider weekly tamoxifen if radiotherapy does not prevent gynaecomastia

• Do not routinely offer bisphosphonates to prevent osteoporosis in men receiving androgen withdrawal– More research is needed into the prevention and management of

osteoporosis in men receiving long-term withdrawal deprivation therapy (NICE)

Case Study

• Jim is a 66-year-old retired accountant who comes to see you with his wife. He has always enjoyed good health and is an active walker. He is reluctant to discuss any symptoms associated with his 'waterworks' and puts these problems down to 'old age‘

• His wife is concerned that he has been getting up more frequently than usual at night to go to the toilet; she adds that he seems to be taking longer to return to bed. She is becoming more anxious about her husband's symptoms as her brother developed similar symptoms a few years ago and was subsequently diagnosed with prostate cancer

• Together they think that an urgent medical opinion is needed. During his subsequent GP consultation Jim admits to having to get up at 2-3 times at night to go to the toilet, but denies having lost weight or having developed any additional aches or pains. His GP considers that the symptoms may be due to a urinary obstruction

What would you do next?

• A PSA test and DRE are appropriate if the symptoms are considered to be due to obstruction, but it is best to exclude the possibility of an infection before offering the test

• Patients presenting with symptoms suggesting prostate cancer should have a DRE and PSA test after counselling

• Symptoms will be related to the lower urinary tract and may be inflammatory or obstructive

• Prostate cancer is also a possibility in male patients with any of the following unexplained symptoms:– Erectile dysfunction– Haematuria– Lower back pain– Bone pain– Weight loss, especially in the elderly

• If Jim had any of these symptoms then he should also be offered a DRE and a PSA test

• Urinary infection should be excluded before PSA testing, especially in men presenting with lower urinary tract symptoms. The PSA test should be postponed for at least 1 month after treatment of a proven urinary infection

• Jim's urine test does not indicate the presence of bacterial infection. Jim's GP offers him a DRE and a PSA test. Jim agrees to the DRE, which reveals no abnormal findings. He has read about PSA testing on the internet but isn't sure whether it's right for him and asks his GP's advice

Which of the following statements are true

• Men with prostate cancer tend to have higher levels of PSA in their blood but up to 10% of men have normal levels

• There is a clear criterion below which men may be reassured that they do not have prostate cancer, and an agreed level that is considered diagnostic

• PSA may also be increased by conditions other than cancer, for example benign prostatic hypertrophy (BPH) and urinary infection and levels tend to increase naturally with age

• Different assay systems can produce different results and levels can vary in response to exercise, sexual activity, clinical investigations and some other forms of treatment

• PSA is found in two forms in the bloodstream - either bound to another protein or free. The greater the proportion of PSA that is bound, the more likely the occurrence of prostate cancer. A free to total PSA ratio of less than 20% and PSA velocity of greater than 0.75 ng/mL/year are accepted as being associated with a higher risk of prostate cancer

• False (Although estimates vary, up to 30% have normal levels) Men with prostate cancer tend to have higher levels of PSA in their blood but up to 10% of men have normal levels

• False (There is no clear criterion) There is a clear criterion below which men may be reassured that they do not have prostate cancer, and an agreed level that is considered diagnostic

• True PSA may also be increased by conditions other than cancer, for example benign prostatic hypertrophy (BPH) and urinary infection and levels tend to increase naturally with age

• True Different assay systems can produce different results and levels can vary in response to exercise, sexual activity, clinical investigations and some other forms of treatment

• True PSA is found in two forms in the bloodstream - either bound to another protein or free. The greater the proportion of PSA that is bound, the more likely the occurrence of prostate cancer. A free to total PSA ratio of less than 20% and PSA velocity of greater than 0.75 ng/mL/year are accepted as being associated with a higher risk of prostate cancer

• After discussion Jim agrees to a PSA test, as he thinks it would be good to be able to rule out the possibility of prostate cancer

• Jim's PSA results are 4.2 ng/mL. The age-specific cut-off PSA measurements recommended by the Prostate Cancer Risk Management Programme are as follows: – Aged 50-59 years >= 3.0 ng/mL– Aged 60-69 years >= 4.0 ng/mL– Aged 70 years and older >= 5.0 ng/mL

What course of action would you now advise?

• Repeat PSA testing in the next 3 months

• Discuss accuracy and validity of this with Jim and agree a plan

• After 6 months, Jim's repeat PSA test results have increased from 4.2 to 5.0 ng/mL

Is an urgent referral (within two weeks) the recommended course of action?

• Jim's PSA level has risen rapidly since his baseline test (greater than 0.75 ng/mL/year) therefore an urgent specialist referral is appropriate

• Jim attends the urology outpatient clinic, and, after discussion with the urologist, agrees to have a biopsy performed. He is subsequently diagnosed with clinically localised prostate cancer

What does NICE advise about the treatment options available?

• Recommended treatment options for localised prostate cancer include:– Watchful waiting– Active surveillance– Radical prostatectomy– External beam radiotherapy (EBRT) – Brachytherapy

• Of these, active surveillance, a method of managing men with low or intermediate-risk localised prostate cancer that, aims to target radical treatment only, to those who would benefit most is the preferred option for men with low-risk cancer. Active surveillance is particularly suitable for a subgroup of men with low-risk localised prostate cancer who have clinical stage T1c, a Gleason score of 3+3, a PSA density of less than 0.15 ng/mL/mL and who have cancer in less than 50% of their total number of biopsy cores with less than 10 mm of any core involved