Episode 5

The role of magnetic resonance imaging (MRI) as a tool to detect and stage clinically significant prostate cancer (csPCa) continues to cause controversy among the medical community.

The 19th Asia-Pacific Prostate Cancer Conference (APCC) held in Brisbane last month dedicated an entire session to the dispute, inviting prominent urologists such as Dr Phil Dundee of the Royal Melbourne Hospital and Samir Taneja MD – Professor of Urologic Oncology at NYU Langone Health – to go toe-to-toe on what is considered one of the most polarising topics in modern urology.

Both have a long track record of contributing to the debate, with Dundee taking on a more conservative stance in Brisbane as he talked about the importance of tissue biopsy to verify normal MRI outcomes – indicating that imaging might not be advanced enough for use in early cancer detection just yet.

According to Taneja, meanwhile, there is evidence that imaging may not only serve as a tool to overcome the shortcomings of conventional transrectal ultrasound-guided biopsies (TRUS-GB), but also help urologists decide whether or not to perform a biopsy in the first place.

“In the pre-biopsy setting, MRI has evolved into a non-invasive tool for prostate cancer risk-stratification that can influence the decision whether to perform biopsy,” he wrote in a 2017 paper titled Magnetic Resonance Imaging In Prostate Cancer.

MRI pre-biopsy?

The underlying goal is the same X-ZELL is pursuing with our new liquid biopsy, X-ZELL Prostate™: to avoid the shortcomings of conventional biopsy – especially false-negative results as well as over-diagnosis and -treatment of insignificant disease – and improve patient experience.

But while research is confident that MRI-assisted biopsies (MRI-TB) already outperform TRUS-GB in the detection of csPCa (in turn reducing the risk of over-diagnosis), the verdict is still out on whether they also serve as a diagnostic tool before the first biopsy.

To date, the majority of research on MRI as a pre-biopsy tool has been focused on the technology’s ability to improve biopsy outcomes by allowing for more accurate targeting, not to avoid them entirely.

In 2011, for example, Haffner et al. retrospectively analysed the results of MRI-TB in patients with suspicious MRI compared to 12-core systematic biopsies in men independent of MRI. In a series of 555 patients, they showed that MRI-TB could have avoided the “potentially unnecessary” diagnosis of 13% of non-significant PCa.

While Haffner’s study did not specifically look into the utility of MRI as a diagnostic tool, it did state that pre-biopsy MRI would be an “attractive potential alternative” to extended systematic biopsies for detection of csPCa, fuelling additional research on the topic.

One of them, conducted by Moore et al. in 2013, went on to review a variety of related studies and found that MRI-TB are able to detect csPCa in an equivalent number of men than standard biopsies, albeit usingfewer biopsies in fewer men and with a 10% reduction in the diagnosis of clinically insignificant cancer – giving a first indication of MRI’s potential as a diagnostic tool.

In 2015, a systematic literature review by Fütterer et al. came to the same verdict, saying multiparametric magnetic resonance imaging (mpMRI) is indeed capable of detecting csPCain biopsy-naïve males – albeit only those with prior negative biopsy.

Fütterer et al. noted the technology’s Negative Predictive Value (NPV) – a crucial measure to verify whether or not MRI can be used to rule out significant disease – ranged from a mediocre 63 to a convincing 98%, once again making a vague case for MRI as a diagnostic tool.

Sufficient data?

At the same time, however, Schoots et al. showcased that in men with clinical suspicion of prostate cancer and a subsequent positive MRI, MRI-TB and TRUS-GB did not differ in overall prostate cancer detection.

Since the publication of these reviews, several key studies have been published and subsequently summarised by Uriburu-Pizarro et al., who concluded that despite some favourable results, robust comparative evidence from randomised controlled trials is still lacking.

Washino et al. came to the same conclusion in 2018, when they found that pre-biopsy mpMRI with subsequent systematic plus targeted biopsies could yield a more clinically significant PCa detection rate than a non-targeted TRUS-GB in biopsy-naïve patients, saying “large prospective studies are needed to confirm our results”.

As such, evidence confirming the utility of MRI as a tool to avoid unnecessary biopsies is still insufficient to warrant clinical introduction, as Ahmad et al. pointedly summarised in 2016: “Although [early] results are promising, there are concerns regarding the implementation of mpMRI in clinical practice.”

According to the Canadian research team, the majority of data on the topic that is currently in circulation has come from centres with high referral rates and extensive experience with mpMRI-TB whose results may not be reproducible in centres with less experience – especially given the fact that even in tertiary referral centres, interobserver variability regarding local extent of disease on prostate MRI is still too high (Riney et al., 2018).

They also pointed out that a standard universal definition of mpMRI–positive results is yet to be determined – arguing that there is no agreement on an acceptable rate of missed significant prostate cancer, and that the long-term impact of mpMRI-TB on patient outcome is not well defined.

Referring to Mozer et al. as well as Pokorny et al., they concluded: “In the PSA era, the majority of prostate cancers diagnosed are of low risk (GS* <7). Although high-volume GS 6 prostate cancer is of concern, it is GS ≥7 disease that is more likely to be consequential. Despite promising initial results, mpMRI-TB failed to demonstrate superiority to systematic biopsy in diagnosing GS ≥7 prostate cancers in biopsy-naïve patients.”

Ahmad et al. also pointed out that mpMRI can still yield false-negative results in 20 to 30% of patients harbouring csPCa.

In line with that, a systematic literature review by Haider et al. concluded that according to current evidence, mpMRI should not be considered in the initial evaluation of biopsy-naïve men at higher risk of prostate cancer, but could be of great use in men with one or more prior negative biopsies and a higher risk of csPCa.

On the reimbursement front, private payers in the US have taken on the same stand. According to 2018 data collated by Booker et al., only 11% of them cover a prostate MRI in biopsy-naïve patients with suspected PCa, with the remaining 89% requiring a prior negative biopsy.

Why does it matter?

With a vast body of early, often specialist-driven research, yet little statistically significant data, the true utility of MRI pre-biopsy is therefore still to be determined – both clinically and economically.

Until a final verdict is out, affordable liquid biopsies such as X-ZELL Prostate™ may thus serve as the missing link between PSA screening and biopsy, MRI-guided or not.

In fact, it may even help doctors justify moving straight to MRI-TB without risk of adding excessive cost to the healthcare system – an issue that has been hotly debated ever since Villers et al. found that pre-biopsy MRI “implies adapting resources, both in terms of staff and of equipment, and requires initial investment”.

As such, X-ZELL Prostate™ may be just the right tool to solve one of the most pressing questions in modern urology, paving the way for more targeted patient care and less waste throughout the diagnostic decision-making process.

*Gleason Score