ERSPC Background

Prostate cancer is the second leading cause of cancer death in men in Western Europe and the United States. Worldwide, more than 670,000 men are diagnosed with prostate cancer every year, accounting for one in nine of all new cancers in males. It is the second most common cancer in men after lung cancer.

Around 225,000 cases are diagnosed each year in Europe alone and 240,000 in the USA. The highest incidence rates are in the United States and Sweden and the lowest rates are in China and India. The extremely high rate in the USA (125 per 100,000) is more than twice the reported rate in the UK (52 per 100,000).

The lowest European rates are in southern and Eastern Europe, while the highest rates are found in countries in Scandinavia and northern Europe.

ERSPC – objectives^

The European Randomized study of Screening for Prostate Cancer (ERSPC) was established more than 12 years ago and is the largest ever randomized study on screening for prostate cancer.

The identification of risk groups in the population is crucial to reducing over diagnosis and over treatment of prostate cancer. Until now there has been no safe way of separating those patients whose cancer will not progress from those that require immediate treatment.

This is a major European effort involving 184,000 men in eight countries – Netherlands, Sweden, Finland, Belgium, France, Spain, Italy and Switzerland.

The study and the related quality of life research should result in evidence-based advice to governments around the world – answering the pivotal question whether screening leads to an improvement of cancer-specific survival and identify men at risk. It will also address the quality of life during screening, and the role of serum markers.

Study protocol^

Study protocol ERSPC


 Admission criteria^

Admission criteria ERSPC


Background to the work of the ERSPC^

Comments from the two co-founders

Views of Prof Louis Denis^

There is no question in the minds of screening public health experts that this study is needed to provide a clear answer to an important health policy question – Do men over fifty years of age need screening for prostate cancer. The answer is not as yet known, as stated in the 2003 publication of the European Code against Cancer.

However, we live in an era of fast track communication where little patience is shown to a study that takes the 15 year natural history of prostate cancer into account and where innovations in diagnosis and treatment of prostate cancer are often seen as giving the answer to the question of screening and where questions on public health are sometimes met with suspicion on its stand towards the individual.

There is now a situation of compromise in the medical community that the individual man requesting the well known PSA-test should be fully informed on its consequences.

These consequences are all part of the study in asymptomatic men aged between 55 and 70 years of age where not only survival but also quality of life and cost/benefit to public health are involved but where aspects of pathology, marker biology and quality control of all aspects of the disease and the study are involved.

Co-founder Prof Fritz Schröder commenting on^

What are the risks of screening?^

The value of screening, the use of early detection measures on the basis of the whole population, can only be proven by showing a reduction in the chance of dying of prostate cancer at an acceptable price in terms of quality of life. Until this study is published we will have no answer to this. At this time screening offers the possibility to diagnose early aggressive prostate cancer that may lead to suffering and death from this disease.

On the other hand, screening may also detect cancers, which do not form a threat to the patients’ life. Finding such cases cannot be avoided at present. It has been estimated that for screening in the general population the number of such minimal cancers is more than 50 % (Draisma 2003). Their diagnosis is actually unnecessary and leads to unnecessary treatment which may be associated with side effects.’

What are the benefits of screening?^

Screening has the potential to find aggressive and potentially killing cancers at an early, still curable stage.

Surgery and radiotherapy are the potentially curative forms of management that are commonly applied. There is now evidence from a separate randomized trial showing that radical prostatectomy decreases the change of dying of prostate cancer with respect to delayed treatment by suppressing the male hormone testosterone. However, even in the delayed treatment group at eight years only about 25% of men are at risk of developing metastatic disease.

Up to now it has been impossible to diagnose early those cases that may not progress and whose carriers may die of some other cause rather than from prostate cancer, without resource to invasive treatment and current detection methods.

The results of the ERSPC trial is expected to give important data on whether the same favourable results of surgery can be achieved in men whose prostate cancer has been detected by screening. Men who decide to be screened currently take a chance. However, men who are well informed about the potential risks and benefits of screening and subsequent treatment should not be denied the early diagnostic tests.

What are the other ongoing studies worldwide that contribute to the questions of screening?^

The great hope is vested in the European Randomized Study of Screening for Prostate Cancer (ERSPC) and, in the United States, the Prostate, Lung, Colon and Ovary screening trial (PLCO). A difference in the rate of deaths from prostate cancer is the most important endpoint in both trials.

If a relevant difference of 20% or more is shown in these trials at an acceptable cost in terms of quality of life and money, it can be expected that governments worldwide will introduce screening programs for prostate cancer which will then be included into paid healthcare policy packages. The great hope of all investigators is that this in fact will happen and that early diagnosis can be offered to all men at risk to decrease the burden of suffering and potential death from prostate cancer.

What screening tests are used within the ERSPC?^

For a screening test to be useful, certain conditions must be met: firstly the screening test must indicate subjects with the condition (sensitivity) and those without (specificity).

A good screening test preferably has a high sensitivity and specificity and must be acceptable for the population screened, rapid and ideally non-invasive.

In prostate cancer screening there are basically three tests available which serve as indicators for the need of further testing. These tests are the digital rectal examination (DRE), the transrectal ultrasonography (TRUS) and the serum prostate specific antigen (PSA) level.

DRE: (digital rectal examination)^

There is a tendency to detect larger tumours with DRE, and the risk of detecting clinically insignificant tumours with DRE is low, but depends strongly on the PSA level. On the other hand, small multi focal lesions with an aggressive biologic potential are not detected with DRE alone. The general opinion is that DRE is highly subjective, and variable between different examiners.

Several studies have already questioned the use of DRE in screening programs and found little or no additional beneficial effect of a DRE in men with PSA levels >= 4.0 ng/ml (Catalona 1994, Rietbergen 1997). It is thought that the DRE can have an additional value in detecting (clinically significant) cancer in men with a low “normal” range of PSA (< 4.0 ng/ml) (Eastham 1999, Han 2004).

TRUS: (transrectal ultrasound)^

Similar to the DRE the interpretation is highly dependent on the investigator. Several studies have shown that the value of TRUS as a screening test is limited to detect cancer, but is indispensable for guiding prostatic biopsies and assessing the prostate volume.

PSA: (prostate specific antigen)^

PSA is a protein, that is almost exclusively produced by the epithelial cells of the prostate, in normal and pathologic conditions, such as infection, urinary retention, enlargement of the prostate cancer. Approximately 40% of the patients with organ confined prostate cancer, show no elevation of serum PSA. The problem with PSA testing is the choice of a cut off value for the decision to continue with more invasive examinations such as the prostate biopsy.

F/T PSA ratio:^

To increase the specificity of PSA as a screening tool derivates from PSA are studied.

Total PSA consists of Complex PSA (cPSA) and Free PSA (fPSA). cPSA is serum PSA that is bound to circulating proteins. It has been shown that the proportion of circulating cPSA is higher in patients with carcinoma than in those with benign enlargement. Studies comparing the diagnostic efficacy of cPSA with total PSA and the free to total (F/T) ratio report diverging results.

Screening tests are used to identify men with an elevated risk of having prostate cancer. This suspicion must however be confirmed. The gold standard to prove the presence or absence of prostate cancer is the surgical removal of the entire prostate followed by a histological analysis of the entire gland. Next to this clinically and ethically impossible manoeuvre, there is no superior method to prove the presence or absence of prostate cancer than a prostate biopsy, although it is known that prostate cancers will be missed with this procedure due to sampling errors. Within the ERSPC trial, prostate biopsies were taken (6 to 9 cores) laterally to the mid plain in the peripheral zone where most prostate cancers are located (Stamey1995). The prostate biopsy is a general safe procedure.

Why are different screening intervals within the ERSPC?^

The optimal screening interval is still to be established. The screening interval has varied between 6 months (Catalona) up to studies with only one time screening (Gustafsson). The screening interval is usually determined from the lead-time assessments. Lead-time for PSA detected cancers are long, in the range 3-11 years, and vary according to PSA level. Cancers detected at a lower PSA level have longer lead-time compared to cancers detected at higher PSA levels (Törnblom). As most prostate cancers in a screening situation are detected at a low PSA level (< 10 ng/mL) one may argue that a long screening interval is sufficient.

However, particularly in prostate it is important to diagnose the fast-growing prostate cancers at an early stage while they still are curable The reason is that these cancers probably are those who are responsible for a lot of the mortality while slow-growing cancers are indolent to most of the patients. Such considerations led different ERSPC centres to choose different screening interval (between 1 and 4 years). These differences give ERSPC a unique possibility to establish an optimal screening interval provided that screening is efficacious.

What is the current policy regarding screening for prostate cancer in Europe?^

The council recommendation on cancer screening for the European Union accepted in 2003 states that PSA testing for prostate cancer, though promising, does not meet the criteria of having proved to decrease the cancer-specific mortality, or well known and acceptable benefits and risks, as well as cost-effectiveness. Therefore, prostate cancer screening is not recommended. The statement emphasizes the importance of the randomized trials and specifically cites the ERSPC in this respect.

This position is consistent with the recommendations of an expert panel organized by the World Health Organization (WHO) and the International Cancer Union, which stated that sufficient evidence showing the benefits of prostate cancer screening in terms of mortality reduction is still to emerge. Therefore, offering screening as part of health care policy can not be recommended without further evidence.

Similar conclusions about withholding screening due to lack of evidence have also been reached in assessments of the U.S. Preventive Services Task Group and the U.S. National Cancer Institute.

Nevertheless, screening does take place even if it is not part of the policy. This is done on the basis of judgment and the responsibility of individual physicians and their patients, who may in some circumstances, regard the possibility of benefit as more important than lack of demonstrated effectiveness.

What information is available for patients within Europe?^

Governments as well as advocates such as general physicians, urologists, and cancer funds supply guidelines for early detection of prostate cancer by PSA-testing. According to most European guidelines PSA-testing should not be offered to asymptomatic men. After request it should only be offered following full counselling about the implications.

For men who consider PSA-testing a number of websites are available, which offer not only guidelines but also information on prostate cancer, prevalence, mortality, treatment options, and pros and cons of PSA-testing. For example:

Packs of clear information sheets (double sided A-4) for distribution by primary care staff to patients are available from the National Health Service in the UK. To order: email