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Main Category: Prostate / Prostate Cancer
Article Date: 24 Sep 2011 ? 0:00 PDT

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Today, at the 2011 European Multidisciplinary Cancer Congress, two new risk indicators for prostate cancer will be revealed.

The investigation, led by Dr David Orsted at the Copenhagen University Hospital, Herlev, reveals that men who are diagnosed with benign prostate enlargement have a higher risk of developing and dying from prostate cancer. The second investigation reveals that the long-term risk of healthy men developing and dying from this disease can be predicted by monitoring prostate-specific antigen levels. As a result these investigations could lead to more efficient and cost-effective screening for prostate cancer, with reductions in over-diagnosis and unnecessary treatment.

In Europe each year, more than 70,000 men die from prostate cancer according to European Cancer Observatory statistics. Prostate cancer shares common features with benign enlargement of the prostate gland (benign prostatic hyperplasia). In both conditions, the growth of the gland is dependent on hormone levels, and both prostate cancer and benign prostatic hyperplasia respond to anti-androgen treatment, however, up till now it was not believed that benign prostatic hyperplasia was a precursor to tumor development.
The investigators studies the connection between the two conditions by analyzing data from five national registries, on a total of 3,009,258 men from Denmark.

53,315 diagnoses of prostate cancer and 25,459 cases of death due to the disease, were included in the sample. Between the years 1980 and 2006, clinical benign prostatic hyperplasia was concluded by records of men hospitalized (187,591) and/or if they underwent surgery for the condition (77,698 men), as well as the use of certain medications suggested for the condition between the years 1995 and 2006 (143,365 and 47,465 men respectively for the two treatments). The reference group consisted of men without benign prostate hyperplasia.

Over the 27 years, they discovered that clinical benign prostate hyperplasia was connected to a two to three times increased risk of men developing prostate cancer, and a two to eight times increased risk from dying from the disease.

Investigation team member Dr. Stig Bojesen will explain to the congress:

?Benign prostatic hyperplasia and prostate cancer and the most common prostatic conditions with a large number of incident and prevalent cases each year. A possible association has been debated for several years but previous studies have generated ambiguous results.?

Further investigations are required to find out if benign prostate enlargement could be a potential cause of prostate cancer, but given the large number of individuals affected, the results already have important implications. Dr. Bojesen says:

?The possible clinical implication of our study might be that physicians treating men with benign prostatic hyperplasia should follow these men carefully, to ensure early diagnosis and treatment of a possible prostate cancer, thereby enhancing the chance of curative treatment. However, our study does not allow us to suggest the optimal surveillance program for these men. This question should be addressed in future studies.?

The second Danish study, also led by Dr ?rsted, looked at whether prostate-specific antigen levels could predict prostate cancer incidence and mortality in the general population.

Prostate-specific antigen is a protein produced by the prostate gland. Men who are healthy have low levels of the antigen in their blood, however, raised levels are believed to be a sign of prostate cancer in addition to other conditions of the prostate gland. Though, it is not clear if antigen levels in men that are healthy predict long-term risk of developing prostate cancer.

Blood collected from 4,383 men between the ages of 20 and 94 from the general population who participated in the Copenhagen City Heart Study and followed from 1981 through to 2009, was examined by the investigators. The researchers measured baseline levels of prostate specific antigen and examined if this related with prostate cancer occurring later and mortality.

Throughout the 28 years of follow-up that was covered by the Heart Study, 170 men who participated developed the disease and 94 died from prostate cancer. While measuring the antigen levels, they discovered that stepwise increases in prostate-specific antigen predicted a 3 to 44 times increased risk of developing prostate cancer and a 2 to 12 times increased risk of dying from prostate cancer.

For men with prostate-specific antigen levels of 4.01-10.00 ng/ml the 10-year absolute risk for developing prostate cancer was 11-22%, compared to the risk of 37-79% in men whose levels were above 10.00 ng/ml, they discovered.

Dr. ?rsted will explain to the congress that the ranges are wide and the higher risk for some men can be explained:

?The high risk for some men is probably due to some of the participants having already developed sub-clinical prostate cancer at the time of their entry to the study. These men would have had a shorter time from study entry to diagnosis and consequently, higher risk estimates.?

The results from the investigation could be used to target certain sections of the population for screening. Dr. ?rsted said:

?One of the major problems in prostate cancer is over-diagnosis. Furthermore, two large randomized studies have shown that the benefit of general screening for prostate cancer is limited. Our results indicate that physicians could focus screening efforts on men with higher baseline prostate specific antigen values while men with lower levels could avoid having frequent and unnecessary diagnostic examinations. This could reduce over-diagnosis and unnecessary treatment as well as reduce expenditure in already strained healthy systems.?

President of ECCO, Professor Michael Baumann, explained:

?These studies demonstrate how important it is to have good cancer registries and skilled cancer epidemiologists available. Large cancer registries, which contain high quality data and link to several items, enable us to address specific questions; for example, whether there is a link between benign prostate hyperplasia or long-term PSA levels and the risk of prostate cancer. Such research allows us to draft hypotheses for further research and to create more efficient screening and prevention programs.?

ESMO spokesperson, Professor Hein Van Poppel, Director of the European School of Urology, said:

?The first study indicates the need for future research to focus on how to follow patients with benign prostatic hyperplasia in order to recognise an eventual cancer in time. PCA3, genetic fusion markers or methylation markers could be explored for this purpose.
For PSA screening, the ideal screening timetable needs to be investigated. It could well be that screening needs to start at an age where there is no interference from the benign prostatic hyperplasia in PSA production, i.e. at age 40; by repeating the PSA measurement at 45 and 50 years old, the PSA slope can probably recognize those with a high likelihood of ever developing cancer, but also those who will not need further screening because their chance or ever developing significant prostate cancer is minimal.?

Written by Grace Rattue

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