Key clinical points

NICE cancer referral guidelines for prostate cancer suggest the following:


Refer men using a suspected cancer pathway referral (for an appointment within 2 weeks) for prostate cancer if their prostate feels malignant on digital rectal examination.

Consider a prostate‑specific antigen (PSA) test and digital rectal examination to assess for prostate cancer in men with:
  • any lower urinary tract symptoms, such as nocturia, urinary frequency, hesitancy, urgency or retention or
  • erectile dysfunction or
  • visible haematuria.

Refer men using a suspected cancer pathway referral (for an appointment within 2 weeks) for prostate cancer if their PSA levels are above the age‑specific reference range.

Introduction

Prostate cancer is now the most common cancer in adult males in the UK and is the second most common cause of death due to cancer in men after lung cancer.

Epidemiology

  • Incidence: 170.00 cases per 100,000 person-years
  • Peak incidence: 70+ years
Condition Relative
incidence
Benign prostatic hyperplasia29.41
Prostate cancer1
<1 1-5 6+ 16+ 30+ 40+ 50+ 60+ 70+ 80+

Aetiology

Risk factors
  • increasing age
  • obesity
  • Afro-Caribbean ethnicity
  • family history: around 5-10% of cases have a strong family history

Clinical features

Localised prostate cancer is often asymptomatic. This is partly because cancers tend to develop in the periphery of the prostate and hence don't cause obstructive symptoms early on. Possible features include:
  • bladder outlet obstruction: hesitancy, urinary retention
  • haematuria, haematospermia
  • pain: back, perineal or testicular
  • digital rectal examination: asymmetrical, hard, nodular enlargement with loss of median sulcus

Referral criteria

NICE cancer referral guidelines for prostate cancer suggest the following:


Refer men using a suspected cancer pathway referral (for an appointment within 2 weeks) for prostate cancer if their prostate feels malignant on digital rectal examination.

Consider a prostate‑specific antigen (PSA) test and digital rectal examination to assess for prostate cancer in men with:
  • any lower urinary tract symptoms, such as nocturia, urinary frequency, hesitancy, urgency or retention or
  • erectile dysfunction or
  • visible haematuria.

Refer men using a suspected cancer pathway referral (for an appointment within 2 weeks) for prostate cancer if their PSA levels are above the age‑specific reference range.

Investigations

The traditional investigation for suspected prostate cancer was a transrectal ultrasound-guided (TRUS) biopsy. However, recent guidelines from NICE have now advocated the increasing use of MRI as a first-line investigation.

Complications of TRUS biopsy:
  • sepsis: 1% of cases
  • pain: lasting >= 2 weeks in 15% and severe in 7%
  • fever: 5%
  • haematuria and rectal bleeding

Multiparametric MRI is now the first-line investigation for people with suspected clinically localised prostate cancer.
  • the results are reported using a 5‑point Likert scale

If the Likert scale is >=3 a multiparametric MRI-influenced prostate biopsy is offered

If the Likert scale is 1-2 then NICE recommend discussing with the patient the pros and cons of having a biopsy.

Management

Localised prostate cancer (T1/T2)

Treatment depends on life expectancy and patient choice. Options include:
  • conservative: active monitoring & watchful waiting
  • radical prostatectomy
  • radiotherapy: external beam and brachytherapy

Localised advanced prostate cancer (T3/T4)

Options include:
  • hormonal therapy: see below
  • radical prostatectomy
  • radiotherapy: external beam and brachytherapy

Metastatic prostate cancer disease - hormonal therapy

Synthetic GnRH agonist
  • e.g. Goserelin (Zoladex)
  • cover initially with anti-androgen to prevent rise in testosterone

Anti-androgen
  • cyproterone acetate prevents DHT binding from intracytoplasmic protein complexes

Orchidectomy

Screening and prevention

Prostate specific antigen (PSA) is a serine protease enzyme produced by normal and malignant prostate epithelial cells. It has become an important tumour marker but much controversy still exists regarding its usefulness as a screening tool.

The NHS Prostate Cancer Risk Management Programme (PCRMP) has published updated guidelines in 2009 on how to handle requests for PSA testing in asymptomatic men. A recent European trial (ERSPC) showed a statistically significant reduction in the rate of death prostate cancer by 20% in men aged 55 to 69 years but this was associated with a high risk of over-diagnosis and over-treatment. Having reviewed this and other data the National Screening Committee have decided not to introduce a prostate cancer screening programme yet but rather allow men to make an informed choice.

Age-adjusted upper limits for PSA were recommended by the PCRMP:

AgePSA level (ng/ml)
50-59 years3.0
60-69 years4.0
> 70 years5.0

However, NICE Clinical Knowledge Summaries currently suggest a different cut-off:
  • men aged 50-69 years should be referred if the PSA is >= 3.0 ng/ml OR there is an abnormal DRE
  • note this is a lower threshold than the PCRMP 60-69 years limits recommended above

PSA levels may also be raised by*:
  • benign prostatic hyperplasia (BPH)
  • prostatitis and urinary tract infection (NICE recommend to postpone the PSA test for at least 1 month after treatment)
  • ejaculation (ideally not in the previous 48 hours)
  • vigorous exercise (ideally not in the previous 48 hours)
  • urinary retention
  • instrumentation of the urinary tract

Poor specificity and sensitivity
  • around 33% of men with a PSA of 4-10 ng/ml will be found to have prostate cancer. With a PSA of 10-20 ng/ml this rises to 60% of men
  • around 20% with prostate cancer have a normal PSA
  • various methods are used to try and add greater meaning to a PSA level including age-adjusted upper limits and monitoring change in PSA level with time (PSA velocity or PSA doubling time)

*whether digital rectal examination actually causes a rise in PSA levels is a matter of debate