Differentiating between aggressive and indolent prostate cancers

University of Newcastle Professor Hubert Hondermarck and his colleagues have found that neurotrophic growth factors, which are overproduced in prostate cancer cells, may be better at separating aggressive prostate tumours from indolent tumours or benign growth than the existing prostate-specific antigen (PSA) test.  
 
‘The [PSA] test is very good, but it has one limitation – it doesn’t show the difference between the types of tumour,’ Professor Hondermarck told newsGP.
 
‘What we hope with our new test is to have a way to tell from blood testing if we are dealing with an aggressive or indolent tumour or a benign hyperplasia, so that at the time of initial diagnosis, we can tell if it’s dangerous or not.’
 
The cancer neurobiology researchers, including Professor Jim Denham and Associate Professor Phil Jobling, received $318,000 in funding from the NSW Cancer Council this week to continue their work on nerve growth factors in prostate cancer.
 
The research comes after a new BMJ Open study found that two fifths of prostate cancers in Australia were over-diagnosed, which often leads to overtreatment and significant negative side effects.
 
Prostate cancer is the second-most commonly diagnosed and second-most common cause of cancer death for Australian men, with around 19,500 diagnosed and 3300 dying from the disease each year.
 
Early diagnosis rates increased rapidly after the PSA test became widely available. A key issue is that many men are diagnosed with prostate cancers that turn out to be very slow growing and pose minimal threat.
 
The new biomarker also holds the possibility of being able to halt cancer progression by tackling the nerves that the cancer uses to grow.
 
Professor Hondermarck said nerve infiltration into a tumour can make it aggressive.
 
‘In animal models, if you cut the nerves into the prostate, the cancer doesn’t grow any more. But it is not so easy just to cut the nerves [in humans],’ he said. ‘They have a function, controlling the prostate.
 
‘What we will work on is preventing the outgrowth of new nerves into the tumour. The nerves already in place would stay.’

According to Professor Hondermarck, nerve cells secrete neurotransmitters and growth factors, both of which can stimulate cancer growth, while the cancer cells can secrete neurotrophic growth factors able to attract nerves.
 
Associate Professor David Smith, head of the prostate cancer research group at Cancer Council NSW, said the research his organisation is funding is producing ‘novel results’ and is much needed.
 
‘There’s been work in this area for at least the last decade and it’s gathering momentum. We really need a better test,’ he said. ‘The PSA test is very good at finding problems in the prostate, but it’s not the diagnostic test – that’s a biopsy and multiparametric MRI [magnetic resonance imaging].
 
‘This research has the potential to save resources and morbidity due to over-detection.’


What type of prostate cancer is it?
 
Associate Professor Smith said that prostate cancer testing is a controversial area because, for many men, slow-growing prostate cancers would often never become clinically apparent or shorten their lives.
 
‘What the PSA test has done is enable lots of men with slow-growing prostate cancers to have investigations that resulted in a diagnosis,’ he said.
 
Diagnosis can then lead men – even with low-risk cancers – to seek radiation therapy or radical prostatectomy, which can cause incontinence and impotence.
 
Guidelines issued by the Cancer Council in conjunction with the Prostate Cancer Foundation state that choosing to have a test is a ‘hard decision’.
 
‘This is because it is hard to tell whether a cancer found after having a test will spread or not, and whether it will cause problems during the man’s lifetime,’ the guidelines state. ‘Thus, men will need to decide whether to have their prostate removed [radical prostatectomy], or treated with radiation [radiotherapy], without knowing for sure the treatment is really necessary.’
 
Associate Professor Smith recommends that men make an informed decision before they get tested, and weigh up the harms associated with diagnosis and treatment against the potentially modest survival gains.
 
‘We recommend that if men wish to embark on testing, that they do so from age 50 by making an informed decision, and have a PSA blood test every two years,’ he said.
 
Associate Professor Smith said that active surveillance – which is now recommended for men with very low-risk prostate cancer – is a much better option than invasive treatment.
 
‘Because of the widespread use of PSA testing, the vast majority of these cancers are diagnosed at an early stage. [Patients’] gut reaction is – I’ve got cancer, get it out,’ he said.
 
‘But in prostate cancer with very low risk of progression, surveillance is a much better option.’
 
A recent MJA study has found that almost 75% of men with low-risk prostate cancers did not undertake the recommended active surveillance follow-up investigations.
 
Associate Professor Smith believes GPs are at the coal face in terms of the discussions required with patients.
 
‘Until the results of this work progress, the best marker of symptomatic prostate problems is the PSA test,’ he said. ‘So having robust, detailed discussion with men around these risks, their own attitudes to the potential benefits and harms is necessary prior to being tested.’
 
The RACGP’s Guidelines for preventive activities in general practice (Red Book) does not recommend PSA screening for asymptomatic (low-risk) men, as the benefits have not been clearly shown to outweigh the harms.
 
‘GPs have no obligation to offer prostate cancer screening to asymptomatic men,’ the Red Book states.
 
The RACGP also has a decision-making guide for men wondering whether to have prostate cancer screening.

medical research neurobiology prostate cancer testing