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Blood samples could hold the key to diagnosis of prostate cancer.

Many men are affected by prostate cancer. Measuring a protein, called PSA, in the blood can help detect the disease before it progresses too far to be treated. An extensive clinical study compared different testing methods and revealed the level at which cancer should be diagnosed and treated. So that PSA testing kits can be validated for accuracy, the partners also produced a certified PSA reference material.

 

Prostate cancer is the second most common cause of cancer-related deaths in men. The cancer progresses relatively slowly in the early stages, giving doctors a reasonable amount of time to catch and cure the disease. Unfortunately, in spite of the availability of innovative and improved tools, the cancer is still diagnosed too late.

Prostatic specific antigen is a protein made in the body. It stimulates the production of antibodies which then try to attack the tumour. Recently, a study in the United States tested the relationship between prostate cancer and the amount of PSA present in the blood. A thousand randomly selected men between the ages of 45 and 80 took part. A quarter of the men with PSA levels above a cut-off limit (3.0 micrograms/litre) were diagnosed with the cancer while only 1 man in 77 with PSA levels below the cut-off limit showed the disease.

This evidence suggested that what one might expect is true: if a man has the cancer, his body will make more of the antigen. It seemed that PSA level measurement could be used as a selective and sensitive tool for diagnosis. This is now well recognised across the Atlantic where the American Cancer Society recommends that men with more than 4.0 micrograms/litre of PSA should be further examined and treated.

A European study

While several systematic studies had been completed in the USA and Canada, not much work had been done in Europe until four organisations from France, Greece and Germany decided to rectify the situation. First of all, they designed and completed a clinical study to screen men for early prostate cancer diagnosis. The team tested blood samples from about 700 men, using five different methods then in use in the European Union, including the test called "Hybritech" which is considered as a reference method in the USA. Comparing the five different methods highlighted discrepancies between the results they produced and thus the necessity for a common calibrator.

Any men with PSA levels over the cut-off limit of 3.0 micrograms/litre had further testing, namely trans rectal ultra sonography (TRUS) or if necessary TRUS assisted biopsies. Correlating the blood tests against cancer detection by TRUS or biopsy showed that cancers would have been missed if the cut-off had been set at 4.0 micrograms/litre instead.

Promising performance

"The clinical trials showed that PSA is one of the most promising tumour markers for prostate cancer at present and it is very likely to remain so for the next 20 years. Its merits, namely sensitivity, specificity and cost effectiveness in diagnosing early stage prostate cancer are now firmly established," says Dr John Kibouris who led the clinical study in the project.

In seeing discrepancies between the results of the test methods, the participants realised that European PSA test kit producers and their European customers would need to validate their test systems with an EU-PSA standard. This is why they decided to prepare a certified reference material. As this material allows commercial immunological PSA test systems to be standardised, results will be easier to compare. So how is this material used? It has a specific amount of PSA and that amount has been rigorously determined through extensive testing. The material is vital to accurately calibrate commercial kits that measure PSA.

"Preparing a reference material from human seminal fluid is not an easy task," says Dr W. P. Mast whose laboratory produced the materials. It has to be purified without degrading the sample in any way. Samples of the reference material are sent to many different laboratories so a batch is prepared rather than just one vial. This batch must be consistent in composition from sample to sample and it must not alter in composition over time, even if it is sent to a laboratory in a hot climate. For this reason, it must be stored at -20°C.

The researchers preparing the material met all these criteria and produced a batch of PSA that is more than 98% pure. They found that their material is unique because it contains five different forms of the protein. The PSA content of the prepared material was measured by five European laboratories, ready for subsequent certification. They each analysed the amino acids that make up the protein.

Cancer correlation confirmed

As there is a correlation between PSA and cancer, blood tests can be used to diagnose the illness. In the clinical trial, the researchers found a detection rate of 2.8% which is comparable to other screening studies. There was, however a reduction of about 55% in the number of required biopsies. This translates to an average of about half the number of biopsies required per cancer patient.

Reducing the number of biopsies is certainly advantageous to the patient. It also makes diagnosis more economical as blood tests are cheaper to perform. With better tools to work with against prostate cancer, more patients may be diagnosed before it is too late.

 

 

Project Title:  Early diagnosis of prostate cancer and preparation of a certified prostate specific antigen reference material

Programmes: Measurements and Testing
Contract Reference: SMT4-CT95-1605

Cordis DatabaseFor more information on this project,
go to the Cordis Database Record

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