PCA3 test: success story from laboratory to the market place
Friday, 26 September 2008 - Interview with Professor Jack Schalken of the Radboud University, Nijmegen (NL)
The number of prostate cancer cases is increasing rapidly. Fortunately not all these tumours need to be operated - some are slow-growing or indolent. The question remains: how do we reliably establish which tumour is aggressive and which is not? The answer may well be given by the PCA3 (Prostate Cancer Gene 3) test, commercially available for over a year. The genetic test was developed in the laboratory of the Radboud University in Nijmegen (NL) by a team headed by Professor Jack Schalken. Schalken spoke about the potential of PCA3 and his expectations.
Q: The PCA3 test means a breakthrough in the diagnosis of prostate cancer, since it is more specific for aggressive tumours. How much more specific is it?
Professor Schalken: “The test has a specificity of over 80%, while the specificity of PSA testing is 25%. The PSA test is not at all selective for aggressive cancers while the cancers PCA3 detects are aggressive in 85% of cases.”
“The sensitivity is high as well; 90%. The tumours that were missed had a Gleason score of 7 and were still fairly small. The test would probably have picked them up at a later stage. An interesting study in this respect was published in the October issue of European Urology: Clinical Utility of the PCA3 Urine Assay in European Men Scheduled for Repeat Biopsy by Alexander Haese et al. The study shows that the PCA3 assay may aid in deciding which patients need a repeat biopsy. An increasing PCA3 score corresponds with an increasing probability of a positive repeat biopsy. In this study, the PCA3 score had greater diagnostic accuracy than the percentage of free PSA for predicting repeat prostate biopsy outcome, even at a sensitivity of 80–90%”.
The final answer will have to come from an ongoing study. At present PCA3 tests are only done in a population that were subject to a prior PSA test. At the moment a screening study is being done in Rotterdam to compare the value of PCA3 tests with PSA tests. The results should be published in 2009.
Q: Will the PCA3 test be further refined or developed?
“No, the test is fully developed. ‘PCA3 has left the building’, i.e. our lab, a few years ago. It can, however, be the basis for a marker panel. In the next 2 to 3 years, additional markers will be added that give more information about the presence of a significant cancer”.
“Molecular testing is going through revolutionary developments. In 5 years’ time, PCA3 testing may well be available as a point-of-care test, which means it can be done as a bedside test. This will have an enormous impact on the logistics and efficiency of any clinic; the patient comes in, gives urine and shortly after that you know the PCA3 value. The team can then immediately decide which treatment to offer the patient.”
Q: What was the response of the international urological community to the PCA3 test?
Schalken: ”Positive; the overtreatment caused by PSA screening is so high that a more specific test is welcomed with applause. As we all know, PSA screening causes many patients with indolent cancers to be diagnosed. Overtreatment sometimes occurs in up to 40 or 50% of cases.”
Q: What does the PCA3 test mean for the doctor’s daily practice?
“We will be able to change to a more rational biopsy schedule. At present it is standard practice to take another biopsy when a patient has had a negative biopsy but a positive test and not to take another biopsy when the patient had a negative biopsy and a negative test”.
“But when the biopsy is negative and the PCA3 is very high, the patient may well have a potentially lethal cancer. This will lead to more imaging ((contrast enhanced) MRI, magnetic resonance spectroscopy, PET scan etc). That way cancers that are located in the ventral part of the prostate may be discovered and you can save lives. At the moment the use of PCA3 in active surveillance and screening is investigated. Therefore the place in the doctor’s daily practice could well expand to other indication areas.”
Q: Why was the promotion low key? After all, the PCA3 test is already on the market for a while.
”I believe the urologist should be informed first. This is a new and rather complex tool which should remain in the hands of experts for at least the first few years. We intended to avoid having a patient demand a test from a urologist who does not know anything about it”.
“There are 8 labs specialised in molecular diagnostic in Europe that provide this test; Noviogendix, the laboratory that performs the test in the Netherlands, is one of them. The tests are rather expensive and it takes qualified personnel to perform them. Thus, for reasons of quality, efficiency and costs it is best to have these tests done in specialised laboratories. I am convinced that this is the future for advanced diagnostics.”
Q: What do you expect from this publicity with regard to patients?
“The patient will no doubt actively seek PCA3 testing. “The more the patient is aware of the uncertainties surrounding the diagnosis prostate cancer, the more a test that gives more certainty is welcomed by patients. Patients will definitely try to avoid having to undergo a biopsy when it is unnecessary. Perhaps in time, the general practitioner (GP) will request a PCA3 test. The GP now refers a patient to the urologist based on an elevated PSA score, while he knows that in many cases treatment is not needed.”
Q: Are there any other projects you expect to bring to the market in the near future?
“Yes, but although it is not an invention of my own group, we validated it. The laboratories that now bring the PCA3 test to the market will do so with gene fusion tests. In 60% of patients with prostate cancer, there is a fusion between an androgen-regulated gene (TMPRSS2) and an oncogene (ERG). In a pre-clinical phase it has now been shown that the gene fusion test adds to the PCA3 test; it increases the test’s sensitivity to aggressive cancers by approximately. 10%.”
“I expect a gene fusion test to become available in Europe within 2 years. Despite the fact that it is a US finding by the group of Professor Chinnaiyan from Michigan, it will probably be available in the European market earlier since we have different regulations for the introduction of diagnostic tests”.
Q: Doctors demand and sometimes invent new diagnostic methods. What is the influence of commercial companies, and where do they come in?
Schalken: “They play a pivotal role. In Nijmegen we have a translational research programme so we can bring the science that we develop in the laboratory to the bedside of the patient. We develop research tests; to turn them into a commercially viable product requires unique skills and expertise. A company usually comes in once you have the first proof-of-principle. In the case of the PCA3 test, it costs about $230 million to develop it into a test you can sell. Universities do not have the money, expertise or skills needed for production under Good Manufacturing Practice conditions, etc. Thus, a company is necessary.”
Q: Do you think this type of testing should be part of the national healthcare systems? Is it reimbursed at the moment?
“Reimbursement is an issue; it is different in every European country. However I am convinced that this is transient. The value of the test is such that it will get a place in the diagnostics reimbursement system. We should lobby more, both in Brussels and in local countries, to inform politicians of how important diagnostics can be. Less than 2% of the overall healthcare budget is spent on laboratory diagnostics, which is why people are less concerned about it. Diagnostics can, however, have a vast impact on treatment.”
“One of the best examples is the HER2 test for breast cancer. It is only useful to give expensive therapy if the patient shows over-expression of the HER2 gene. This is crucial for healthcare programmes even though it is in conflict with the interests of pharmaceutical companies; they will sell less. The EAU should develop a strategy in various countries to bring this conflict to the attention of healthcare providers. The EAU Research Foundation is already taking up the challenge. And PCA3 could lead the way here.”
