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Prostate Cancer Screening – the dilemma

Prostate cancer screening with the Prostate Specific Antigen (PSA) blood test

remains a contentious subject in the field of prostate cancer. It is felt that there is not enough evidence to determine whether screening results in a reduction in mortality from the disease.

Three ongoing large, randomised, controlled clinical trials are evaluating the value of PSA screening for prostate cancer:  These are :

The European Randomised Study of Screening for Prostate Cancer (ERSPC),

The Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial in the US

The UK-based Prostate Testing for Cancer and Treatment (ProtecT) study.

The first reports from these trials have been published and have added further information to the PSA screening debate but unfortunately few answers:

The PLCO study reported no mortality benefit with the combination of PSA screening and digital rectal examination (DRE) during a median follow-up of 7 years.

However, the ERSPC trial found that PSA screening was associated with a 20% relative reduction in prostate cancer mortality at a median follow-up of 9 years, this equates to about 7 prostate cancer deaths saved per 10,000 men screened.

Unfortunately this mortality benefit was associated with a high risk of overdiagnosis, with nearly 76% of men who underwent a biopsy following an elevated PSA value having a false positive result.

So in summary screening may not identify significant cancers that actually need treatment and the process risk over diagnosis of low risk cancers – so why is it done?

The most obvious answer is to reassure an individual that their own risk is low particularly if they have a family history and to identify those that are high risk for a diagnosis early so that effective treatment can be offered.

 

NHS Prostate Cancer Risk Management Programme

On the 20th July 2009 Sir Liam Donaldson the Chief Medical Officer wrote to all the GPs in the UK about a Revised Prostate Cancer Risk Management Programme (PCRMP) which gives the opportunity for all men who have concerns about prostate cancer, to have the right to a Prostate Specific Antigen (PSA) blood test free on the NHS. This right should be exercised in the context of genuinely balanced information from their GP about the pros and cons of this test. It is now available free on the NHS.

 

Education, Education, Education

Although the PCRMP is NOT a screening programme it does empower both patient and GP to consider the issues and implications of early prostate cancer diagnosis and treatment. Every single GP has now been distributed packs containing information and materials comprising

  • A reference booklet for GPs discussing all the available evidence
  • A summary sheet for GPs to help in consultations
  • A patient information sheet
  • Cancer Research UK statistics on prostate cancer

A GP will refer to a urologist on the basis of whether a PSA blood test is above the normal range

  • If you are Age 50 – 59 and the PSA is 3.0 ng/ml or higher you will be referred
  • If you are Age 60 – 69 and the PSA is 4.0ng/ml or higher you will be referred
  • If you are over Age 70 and the PSA is 5.0 ng/ml or higher you will be referred

There seems to be no recommendation on values below the age of 50 which suggests the free PSA test will not be available to those aged between 40 and 49 and there is no recommendation to offer PSA testing to men who have a strong family history (2.5 fold increase if father has prostate cancer and 3.4 fold increase if one brother has the disease).

 

Risk factors for prostate cancer

The risk factors for prostate cancer are highlighted here for completeness

Age

Relatively rare in men under the age of 50 years.

Incidence increases in those over 60 years.

Race

A higher incidence of the disease is seen in African-Caribbean, African-American and West African races.

Men of Chinese and Japanese origin have a low incidence of disease.

Geography

The highest incidence of prostate cancer is currently seen in North America and

Northern Europe.

Family history

Men with a first-degree relative affected by prostate cancer have a relative risk of developing the disease themselves 2-fold greater than men with no relatives affected.

Those men with an affected second-degree relative have an increased relative risk of 1.7 of developing the disease.

Men with both a first- and second-degree relative affected have an increased relative risk of 8.8 of developing the disease.

There is also some evidence to show a link between an increased risk of prostate cancer where there is a family history of breast, ovarian, bladder or kidney cancer.

Factors affecting PSA concentrations are summarised below.

 

Age and race (PSA ng/ml)

Age (years)     White              Black               Latino              Asian

40−49              0−2.3               0−2.7               0−2.1               0−2.0

50−59              0−3.8               0−4.4               0−4.3               0−4.5

60−69              0−5.6               0−6.7               0−6.0               0−5.5

70−79              0−6.9               0−7.7               0−6.6               0−6.8

Biopsy/transurethral resection of the prostate (TURP) can cause an increase in PSA for a variable time period (4−12 weeks).

Prostatitis can cause an increase in PSA concentration, which can be reduced to within a normal range with antibiotic treatment, if not a biopsy is indicated

Prostate size – a benignly enlarged gland can influence PSA concentrations.

Infection – elevated PSA levels can be seen beyond 6 months in up to 50% of patients when associated with febrile urinary tract infections.

Free and complexed PSA should be understood. The percentage free PSA is most useful in men with a PSA concentration in the range 2−15 ng/ml the higher the percentage of free PSA the lower the probability of cancer.

Probability of cancer (%)

Total PSA             (ng/ml)          

0−2                         <1 %

  2−4                                          15 %

4−10                                        25 %

>10                                         >50 %

 

Free / Total PSA       (%)

0−10                                        56 %

10−15                                      28 %

15−20                                      20 %

20−25                                      16 %

>25                                            8 %


 

From the above discussion it should be understood that although the PSA test is a useful test to evaluate patients who are at risk of prostate cancer or are concerned enough to request the test that there are a number of variables which introduce a considerable degree of uncertainty in its interpretation and the possible need for a prostate biopsy.

 

A better approach might be to assess men on the basis of the normal Median PSA value for their age. The idea here is that if one knows what the expected PSA should be at a given age any value above that level should be considered suspicious irrespective of whether the PSA was within the reported normal range

 

The Median PSA

 

  • At age 40 this is around 0.6 ng/ml (Normal Range 0 – 2.0 ng/ml)
  • At age 50 this is around 0.9ng/ml  (Normal Range 0 – 3.0 ng/ml)
  • At age 60 this is around 1.2ng/ml  (Normal Range 0 – 4.0 ng/ml)
  • At age 70 this is around 1.5ng/ml  (Normal Range 0 – 5.0 ng/ml)

 

Men who have a PSA below the median value could be positively reassured and simply advised to have another test in 5 - 10 years to confirm that their PSA test remains below the age specific median value.

 

Men who have a PSA above the median value but still below the upper limit of the normal range for their age have an increased risk of prostate cancer.

Risk could then be stratified with the frequency of testing depending on the baseline PSA.

 

Men who have a baseline PSA well above the median value but below the upper limit of normal should have PSA testing combined with a rectal examination of the prostate annually and a low threshold for prostatic biopsy.

 

The bottom line

 

  • If you have a family history and are over 40 demand a baseline PSA
  • If you are 50 and have not had one done then have a baseline PSA
  • If you have a recent change in your urinary symptoms see your GP
  • If you have had a PSA before then find out the result and discuss with your GP
  • If it is increasing, request a further test and referral for a urological opinion
  • Be happy if your PSA is less than the median value for your age
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