Gene test may reduce unnecessary prostate removals

The new test could potentially spare men from unnecessarily having their prostate removed. Jeff Werner

A new test could help doctors better understand which prostate cancers are likely to remain slow growing and could be managed with surveillance only, potentially sparing thousands of men from unnecessary prostate removal surgery or invasive procedures.

Diagnosing the likely rate of a prostate cancer growth is notoriously tricky, leading many clinicians to err on the side of caution and recommend treatment where it may not be needed.

In a new paper published in the journal Science Translational Medicine, researchers from the Columbia University Medical Centre said they had discovered that the expression of certain genes associated with ageing could be used to predict whether a prostate cancer was going to become aggressive or stay indolent (slow growing).

The researchers looked at prostate cancers that had a low Gleason score, a grading system that aims to give patients and clinicians an idea of how aggressive a prostate cancer is.

A low Gleason score means the cancer is currently slow-growing, but until now, there was no way of accurately predicting how long it would stay indolent.

“Distinguishing the many indolent tumours from the minority of lethal ones remains a major clinical challenge,” the researchers wrote in their paper.

“The current lack of reliable and reproducible assays to identify tumours destined to remain indolent has resulted in substantial over-treatment of patients who would not have died from prostate cancer if the disease had been left untreated.”

The researchers discovered that the expression of three genes – called FGFR1, PMP22, and CDKN1A – allowed them to accurately predict the outcome of low Gleason score tumours. Tumours in which this biomarker was not expressed or expressed at low levels were deemed aggressive.

“The three-gene biomarker could take much of the guesswork out of the diagnostic process and ensure that patients are neither over-treated nor under-treated,” said lead author Dr Cory Abate-Shen, lead author of the study and head of the lab that made the discovery.

The researchers put their theory to the test on 43 patients who had been monitored for at least 10 years for a slow growing prostate cancer.

Of the 43 patients, 14 ultimately developed advanced prostate cancer. All 14 were correctly identified by the test, the researchers said.

Holy grail

Ian Haines, Adjunct Associate Professor of Medicine at Monash University said that the new finding was “a useful first step towards the holy grail of prostate cancer diagnosis.”

“This study pursues the noble and so far elusive goal of identifying in advance which low or intermediate risk prostate cancers may become aggressive in their behaviour and eventually threaten the patient’s survival,” said Dr Haines, who was not involved in the study.

“If these preliminary results are replicated in the proposed larger study, this three-gene biomarker will represent a significant advance that will help to define more accurately which patients can be offered watchful waiting as their treatment of early stage prostate cancer.”

Dr Haines said it was important to remember that most prostates have multiple independent sites of cancerous growths.

“Hence, you really have to do the analysis on multiple independent sites,” he said.

Dr Haines said the tests do not help in reducing the over-diagnosis of early stage prostate cancer caused by the use of PSA (prostate-speficic antigen) screening, “but they may prove very effective in helping to reduce the current over-treatment of early stage prostate cancer.”

Ian Olver, Clinical Professor of Oncology at Cancer Council Australia said that to be able to predict which of the low grade prostate cancers is aggressive by a simple three-gene test is “an important finding, if it stands up to further trials.”

“We have not been able to do that from microscopic examination of the cancer. This will mean that we will be able to select which patients with low grade prostate cancers need to be treated immediately, and which can be safely kept under surveillance,” said Professor Olver, who was not involved in the study.

“This will reduce the problem of over-treatment where currently prostatectomies are performed, but the prostate cancer would never have caused a problem. It will also provide more reassurance to men who select a watch policy, that their disease is slow growing.”