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Guide: Prostate Cancer

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  • Background and prevalence
  • Screening
  • Risk factors
  • Symptoms
  • Examination
  • Diagnosis
  • Investigations
  • Prostate-specific Antigen (PSA)
  • Management for localised cancer
  • Prostate cancer risk groups and treatment options
  • Management options for advanced prostate cancer
  • Patient resources
  • References

  • Background and prevalence

    • Prostate cancer is the most commonly diagnosed cancer in Australia and the third most common cause of cancer death.
    • It is predominantly a disease of older men; 85% of cases are diagnosed after the age of 65 years.
    • In 2009, the risk of an Australian male being diagnosed with prostate cancer by 85 years of age was 1 in 5.
    • In 2010, the risk of a man dying from prostate cancer by his 85th birthday was 1 in 25.
    • More than 95% of the malignant neoplasms of the prostate are adenocarcinomas. The rest are transitional cell, squamous cell and small cell carcinoma.


    Screening

    • Evidence does not currently support population-wide screening for prostate cancer.
    • A statement from Andrology Australia (2011) notes:
      Testing levels of prostate-specific antigen (PSA testing) in the blood combined with digital rectal examination (DRE) is widely used in Australia to identify men at risk of having prostate cancer. However, given the absence of evidence for net benefit (benefits exceed harms), testing should be targeted and only be considered for informed individuals.
    • The RACGP (2012) advise:
      GPs need not raise this issue, but if men ask about prostate screening they need to be fully informed of the potential benefits, risks and uncertainties of prostate cancer testing. When a patient chooses screening, both [prostate specific antigen] PSA and [digital rectal examination] DRE should be performed.

    Table 1: Benefits and harms of PSA testing in average-risk* men aged 60 years**

    Possible benefit of PSA testing Expected harms of PSA testing
    • For every 1000 men tested, 2 men will avoid death from prostate cancer before 85 years because of PSA testing (benefit may be greater in high risk individuals).


    • For every 1000 men tested, 2 men will avoid metastatic prostate cancer because of PSA testing.
    False positives
    •For every 100 men tested 87 who do not have prostate cancer will have a false-positive PSA test that will lead to biopsy.
    Overdiagnosis
    •For every 1000 men tested 28 men will have prostate cancer diagnosed, many of whom would have remained asymptomatic.
    Overtreatment
    For every 1000 men tested:
    •25 men will choose to undergo treatment, many of whom would do well without treatment.
    •7-10 of these 25 men will develop impotence/urinary incontinence/bowel problems as a result of treatment.

    *No first-degree relatives with prostate cancer. ** Estimate based on annual PSA testing for 10 years. Adapted from NHMRC, 2014.


    Risk factors

    • Men with one or more first-degree relatives diagnosed before the age of 65 years and men with a first degree relative with familial breast cancer (BRAC1 or BRAC2) are at high risk of prostate cancer.


    Symptoms

    • Unsuspected cancers are often detected PSA or histologically after transurethral resection of the prostate (TURP).
    • Clinical prostate cancer presents typically with rapidly progressive symptoms of lower urinary tract obstruction or of metastatic spread, especially to bone (pelvis and vertebrae).
    • Symptoms include bladder outlet obstruction, acute retention, back or other bony pain, haematuria and uraemia, tiredness, weight loss and perineal pain.


    Examination

    • DRE may reveal hard, irregular, craggy or nodular prostate, but it is only possible to palpate that part of the prostate immediately in front of the rectum and it may feel normal.


    Diagnosis

    • Prostate cancer is usually suspected on the basis of DRE and PSA levels. Definitive diagnosis depends on histopathological verification of adenocarcinoma in prostate biopsy cores or operative specimens.
    • The decision whether to proceed with further diagnostic or staging work-up is guided by which treatment options are available to the patient, taking the patient’s age and comorbidity into consideration.


    Investigations

    • Elevated PSA — see below.
    • Needle biopsy guided by transrectal ultrasound — 10-12 biopsies should be performed. A histological grade or Gleason score is determined from the morphology of the glandular components of the biopsies. The Gleason grade of 1-5, representing low to high grade morphology, is added from two samples to form a score.
    • Side effects of biopsy include infection (prophylactic antibiotics are required), rectal bleeding, haematuria and haematospermia.
    • A combination of serum PSA, biopsy findings and clinical staging is used to stratify patients with prostate cancer into low, medium and high-risk disease.

    Table 2: Risk stratification for men with localised prostate cancer

    Level of risk PSA Gleason score Clinical stage
    Low-risk <10 ng/mL and ≤ 6 and T1-T2a
    Intermediate- risk 10-20 ng/mL or 7 or T2b
    High-risk* > 20 ng/mL or 8-10 or ≥ T2c

    *High-risk localised prostate cancer is also included in the definition of locally advanced prostate cancer.
    Adapted from NICE Clinical Guideline 175: Prostate Cancer, 2014.

    Imaging

    • Imaging is important to exclude disease that has spread beyond the prostate to regional lymph nodes or bone.
    • Imaging is not indicated for staging in low-risk tumours.
    • It may include:
      • Pelvic CT to determine lymphatic spread.
      • Bone scan for identifying bony metastasis.
      • Chest x-ray to correlate with bone scan.
    • The TNM system (size of Tumour, presence of lymph Node involvement and Metastases or distant spread) is used for staging.


    Prostate-specific antigen

    Prostate-specific antigen is a glycoprotein produced solely by the prostate. Serum levels of total PSA > 4.0ng/mL are regarded as abnormal. However, PSA levels rise with normal ageing as the prostate undergoes benign enlargement; thus reference values for PSA must be adjusted for age.
    The test should be repeated after 1-3 months if results differ markedly from expected.

    Factors which may increase PSA levels are:

    1. Benign prostatic hypertrophy (the most common cause)
    2. Prostate and urinary infection and inflammation
    3. Urinary retention
    4. Recent ejaculation (can remain altered for up to 48 hours)
    5. Prostate cancer
    6. Prostate needle biopsy

    Anti-androgens e.g. finasteride lower PSA levels.

    • Patients should be reminded that a normal blood level does not exclude cancer.
    • The half-life of PSA is 2-3 days, and it takes several weeks for the level to drop to zero or baseline after instrumentation or surgery.
    • PSA can be used to follow the response of disease to treatment. Serum PSA should reach undetectable levels after radical surgery. A failure to reach undetectable levels indicates recurrence or metastases.
    • Similarly radiation or hormone therapy should drop PSA levels; subsequent increase would suggest reoccurrence or spread.


    Management for localised cancer

    Treatment decisions are based on life expectancy, co-morbidities and patient preference.


    Prostate cancer risk groups and treatment options

    Low risk Intermediate risk High risk
    Radical prostatectomy Radical prostatectomy Radical prostatectomy
    Low-dose seed brachytherapy External beam radiotherapy External beam radiotherapy
    Active surveillance Low-dose seed brachytherapy High-dose brachytherapy
    • Low-grade disease confined to the prostate can be watched (active surveillance), under the care of a specialist. Patients are monitored closely with regular DREs, and prostate biopsies to identify early those who should undergo definitive therapy.
    • Surgery with curative intent removes the whole prostate (radical prostatectomy). The main side-effects/risks are erectile dysfunction (> 50%) and urinary incontinence (2-10%). Erectile dysfunction (ED) may be minimised by nerve-sparing techniques.
    • Brachytherapy delivers radiation directly to the prostate by transperineal implantation of either permanent radioactive seeds (usually iodine-125, low dose rate), or temporary implant (high-dose rate brachytherapy). Risk of ED is lower than other treatments but can cause significant urinary symptoms, especially in first 6 months.
    • External bean radiotherapy (EBRT) can also be given with curative intent. Side effects are similar to surgery; however bowel problems may also occur. Combined use of EBRT and androgen deprivation has been shown to significantly improve outcomes.


    Management options for advanced prostate cancer

    Hormonal Therapy

    • The mainstay of treatment for metastatic prostate cancer is hormonal ablation or androgen deprivation therapy (ADT).
    • For as long as malignant cells are dependent on androgens for growth, ADT will slow cancer progression.
    • Bilateral orchidectomy (surgical castration) is now rarely used in Australia because of its emotive nature.
    • Medical castration with luteinising-hormone-releasing hormone (LHRH) agonists e.g. leuprorelin, goserelin, triptorelin is equally effective. LHRH agonists are given as subcutaneous injection every 3-4 months.
    • After the first injection, they stimulate pituitary LHRH receptors, inducing a transient ‘testosterone surge’ or ‘flare-up’, which begins 2-3 days later and lasts for about 1 week. Some patients may present with exacerbation of symptoms.
    • Other side effects include hot flushes, erectile dysfunction and loss of libido, osteoporosis, loss of muscle mass, cognitive changes, weight gain, tiredness and breast enlargement.

    Therapy for Hormone-refractory Prostate Cancer

    • In hormone-refractory prostate cancer there is progressive rise in PSA or progression of bone or soft tissue lesions despite hormonal therapy. Prognosis is poor.
    • Chemotherapy e.g. docetaxel combined with prednisolone may produce modest improvements in survival and quality of life.
    • Radiotherapy is an effective and well-tolerated treatment for metastatic bone pain.
    • Bisphosphonates e.g. zoledronic acid may be prescribed to reduce adverse skeletal events (fractures) in patients with bone metastases.
    • Refer for specialist palliative care or a coordinated palliative approach to assist in advance care planning.


    Patient resources

    The following resource can be used when discussing the risks and benefits of PSA testing with patients:
    Andrology Australia show card

    References

    1. Cancer Council of Australia, 2014. Prostate Cancer. www.cancer.org.au/about-cancer/types-of-cancer/prostate-cancer.html (Accessed 23 June 2014)
    2. Australian Institute of Health and Welfare 2014. ACIM (Australian Cancer Incidence and Mortality) Books. Canberra: AIHW.
    3. Frydenberg M, Lenz D. How to Treat: Prostate Cancer, Australian Doctor, 25 February 2005: 29-36.
    4. Andrology Australia, 2011. Andrology Australia Statement on PSA Testing for Prostate Cancer https://www.andrologyaustralia.org/wp-content/uploads/PSA_position_Feb_2... (accessed 20 June 2014)
    5. Royal Australian College of General Practitioners, 2012. 9.8 Prostate cancer in Guidelines for Preventive Activities in General Practice 8th edition. Melbourne: RACGP http://www.racgp.org.au/your-practice/guidelines/redbook/early-detection...
    (Accessed 20 June 2014)
    6. National Health and Medical Research Council, 2014. PSA testing for Prostate Cancer in Asymptomatic Men. NHMRC Ref: MED4d. Canberra: NHMRC https://www.nhmrc.gov.au/_files_nhmrc/publications/attachments/men4d_psa... (Accessed June 20, 2014)
    7. Murtagh J. John Murtagh’s General practice. 5th ed. Sydney: McGraw Hill Pty Ltd; 2011
    8. National Institute for Health and Care Excellence, 2014. NICE Clinical Guideline 175: Prostate Cancer: Diagnosis and Treatment.
    http://guidance.nice.org.uk/CG175 (Accessed 23 June 2014)
    9. European Association of Urology, 2014.Guidelines on Prostate Cancer
    www.uroweb.org/gls/pdf/09%20Prostate%20Cancer_LRLV2.pdf (Accessed 23 June 2014)
    10. Leslie S, Woo H. How to treat: Prostate cancer — Part 2. Australian Doctor 30 July 2010, 23-30.
    11. Duchesne G. Localised prostate cancer: Current treatment options. Aust Fam Physician 2011;40: 768-771.
    12. Cancer Council Australia Advanced Prostate Cancer Guidelines Working Party. Management of locally advanced and metastatic prostate cancer. Sydney: Cancer Council Australia. [Version URL: http://wiki.cancer.org.au/australiawiki/index.php?oldid=78318 Accessed 20 June 2014]. Available from: http://wiki.cancer.org.au/australia/Guidelines:Prostate_cancer/Managemen...
    13. Brett T. Prostate specific antigen. Aust Fam Physician 2011; 40:497-500.