Dr Grummet wrote this article published in the June 2014 edition of Medical Observer.
At last. Through the dark clouds of controversy that have cast shadows over the diagnosis of prostate cancer for so many years, a ray of light is just starting to shine through. That light’s somewhat longwinded name is multiparametric MRI.
Having been involved in the world of urology for the last decade, it is by far the most exciting thing to happen in prostate cancer in that time. But a word of caution: it is not yet indicated for widespread use, as will be explained later. Let’s take a look at the historical context that explains why this new modality has the potential to change the face of prostate cancer diagnosis.
Before PSA testing, prostate cancer was diagnosed by DRE (digital rectal examination) or by men presenting with symptoms of advanced disease. So a high proportion of men’s disease was already incurable at diagnosis. PSA testing has since caused a huge shift towards earlier detection with the benefit of a very high cure rate. As might be expected, a welcome drop in prostate cancer mortality has been observed over this period.
But PSA testing has also led to the overtreatment of low risk prostate cancers that were never destined to cause any harm to one’s health, let alone death. Furthermore, the treatment of localized prostate cancer has potential side effects that may impact greatly on quality of life, such as erectile dysfunction and, less commonly, urinary incontinence.
Critics of PSA screening argued that the small reductions seen in mortality and morbidity of PSA-detected prostate cancers were being outweighed by the harm done by the side effects of treatment. This argument reached its zenith in 2011 when a US Government Taskforce even recommended against PSA screening altogether. This recommendation has been hotly debated since.
However, throughout the last decade it had become well-recognised that the vast majority of low risk prostate cancers were not harmful (hence the name!), and could be safely watched under a program of active surveillance. This strategy enables the avoidance of overtreatment whilst allowing close monitoring, so that any sign of cancer progression can trigger intervention that is still curative.
Active surveillance of low risk prostate cancer has therefore been one of the strongest arguments in favour of persisting with PSA testing, so that we can still detect the cancers that are harmful before it is too late.
However, for all its great benefits, active surveillance seemed to have a flaw. Currently, to remain on active surveillance, it is still considered standard for a patient to need a repeat “confirmatory” biopsy within 12 months of the initial 12 core transrectal (TRUS) biopsy. But up to 30% of these repeat biopsies show higher grade disease that is no longer suitable for observation. Critics of active surveillance cite this as an argument against it, and uptake of active surveillance in the US for example has been poor, with up to 90% of low risk prostate cancers still being treated.
But in fact what these repeat biopsies tell us is that the problem is not so much active surveillance itself, but rather the inaccuracy of the initial biopsy. This has led to an exploration of the more extensive transperineal biopsy, where between 18 and 36 cores are typically taken. The latter approach is performed via the perineal skin rather than through the rectal wall, and recently published Australian data has shown evidence of an increased detection rate of high grade tumours in the anterior part of the prostate, along with a negligible rate of sepsis. This technique therefore represents an exciting advance.
However, like TRUS biopsy, transperineal biopsy still involves blind random sampling of an entire organ - a method which has no real counterpart in the diagnosis of any other solid organ cancer. Both kinds of biopsy can therefore overdiagnose disease that we don’t really want to know about, i.e. low grade, low volume (and therefore very low risk) prostate cancer.
If only there was an imaging modality that, as for other cancers, could allow us to target biopsies to the clinically relevant tumour, and at the same time avoid insignificant disease….. Enter, multiparametric MRI (mpMRI).
MRI has of course been around for many years, but it is only recently that by combining multiple parameters of MRI and reporting in a standardized fashion known as PIRADS, that mpMRI is becoming accurate enough to be of any clinical use. However, it is the groundbreaking research in mpMRI by two Australian groups published in 2014 that may just provide the tipping point.
Pokorny et al performed a prospective study comparing 12 core TRUS biopsy to mpMRI. To check the mpMRI findings, they performed targeted biopsies of suspicious lesions, and found that mpMRI far outperformed TRUS biopsy, with negative predictive values (NPV) for significant cancer of 97% and 72%, respectively. In other words, only 3% of significant cancers were missed by mpMRI versus 28% for TRUS biopsy. As had long been hoped for, mpMRI not only reduced the detection of low risk prostate cancer, but it also improved the detection of higher risk cancer.
Thompson et al compared mpMRI to 30 core transperineal biopsy, for arguably a more accurate assessment of the true presence of cancer. They too found excellent NPVs of 92-96%, depending on the definition of significant cancer used. Again, only 4-8% of significant cancers were missed by mpMRI.
These landmark papers argue in favour of mpMRI playing a significant role in the diagnosis of prostate cancer, and we should be proud that Australian research is leading the way. However, the results need to be validated across larger multi-centre studies. Until then, many questions remain: Should all patients with elevated PSA undergo mpMRI? Can a biopsy really be avoided if the mpMRI is negative? Can mpMRI be used in active surveillance of men with known low risk cancer? MpMRI is therefore by not yet considered standard of care and is currently not reimbursed by Medicare.
And most importantly, the excellent and exciting results seen in these studies were made possible by a small number of radiologists and urologists with immense training and experience in mpMRI. Such expertise is not yet widely available. Any referrals for the test should therefore only be made by urologists to radiologists expert in mpMRI after a thorough discussion with each individual patient.
So we have seen through a short history of the diagnosis of prostate cancer that mpMRI, when performed by experts, may help us finally achieve what we’ve been crying out for - a reduction in the detection of insignificant prostate cancer and an increase in detection of clinically significant disease at the same time. In doing so, mpMRI has the potential to truly change the face of prostate cancer diagnosis. Watch this space!