Largely unnoticed by the general public, early prostate cancer detection recently rose to the very top of the European Parliament’s teeming agenda.

Coinciding with the European Prostate Cancer Awareness Day (EPAD), the EU’s law-making body invited policy makers, scientists, medical societies and patient advocacy groups to Brussels to deliberate how to counteract low awareness for early detection and the ongoing lack of appropriate diagnostic tools – both of which frequently contribute to late diagnoses.

The consensus after a day of intense debate was that there is a pressing need for a population-based screening solution at the EU level – not just to take pressure of healthcare systems, but also to avoid preventable loss of life.

Why we still need PSA

A central talking point during the special parliamentary session was the role of Prostate Specific Antigen (PSA) testing as a tool to facilitate such a broad-based screening effort.

While research has shown that PSA testing can reduce mortality rates by 21%, the test’s inherent risk of over-diagnosis has recently led to a drop in PSA usage in the UK and the US – and with it a troubling rise in mortality, as the European Association of Urology (EAU) pointed out.

“Key evidence has emerged from two independent studies in 2017 and 2018 to demonstrate that a lack of prostate cancer screening is reversing the trends of declining death rates,” the Association said in a report that was launched as part of EPAD19 (see link below).

“Since practitioners in both the UK and the US have been advised not to perform PSA for early detection, worrying statistics are emerging to demonstrate that cancer mortality is increasing.”

The challenge, according to the EAU report, is to make full use of PSA’s positive effect on mortality without exposing patients to over-diagnosis and overtreatment – a balancing act often summarised under the term ‘coordinated screening’.

To do so, the EAU report recommended tapping into new and emerging technologies capable of providing complementary information to clarify inconclusive PSA results, as well as pre-selecting men with low-risk prostate cancer for active surveillance.

Why X-ZELL could fill the diagnostic gap

One such complementary tool is X-ZELL Prostate™, a liquid biopsy designed to provide additional information to doctors confronted with PSA results in the so-called diagnostic grey zone, which have proven to cause the majority of over-diagnoses.

Designed specifically for readings in the 4-20ng/mL grey zone, X-ZELL Prostate™ scans a small blood sample for minuscule traces of tumor-derived Circulating Endothelial Cells (tCEC), powerful biomarkers capable of indicating the presence or absence of clinically significant, early-stage disease.

In doing so, it serves as a highly accurate ‘rule-out’ test to be applied before mpMRI, which recently gained considerable support as a ‘rule-in’ test but has been criticised for giving a false sense of security to individuals that may still harbour disease.

Early research has shown X-ZELL’s novel liquid biopsy may also be useful as a triage test to to channel patients into biopsy or follow up/ rgenetic testing, as well as a tool to detect castration-resistant, non-curable cancers after prostatectomy – making it one of the most promising prostate cancer management solutions in the world right now.

Who or what is X-ZELL?

Headquartered in Singapore, X-ZELL recently made headlines in Europe when company CEO and lead scientist, Dr Sebastian Bhakdi, presented preliminary results of the world’s first prospectively blinded tCEC screening study at the 10th European Multidisciplinary Congress on Urological Cancers (EMUC18) in Amsterdam.

The study, which is currently under review for publication, demonstrated that X-ZELL Prostate™ can avoid more than half of all prostate biopsies and significantly reduce the risk of over-diagnosing clinically insignificant prostate cancer if used as a PSA add-on for patients in the diagnostic grey zone.

As such, it would not only respond to the European Parliament’s call for a PSA-based solution, but also protect patients from over-diagnosis and, as a result, overtreatment. 

Why tCEC work

What’s different about X-ZELL’s tCEC approach – as opposed to the many competing concepts – is that the young company does not have to scan blood for fragments of so-called circulating tumour DNA (ctDNA), which have proven to generate a significant amount of false-negative results and are costly to obtain.

X-ZELL’s robust and cost-efficient approach does not only retain the majority of cell DNA and RNA for downstream analysis, but also avoids loss of cell morphology – thus allowing for a visual classification of the cancer cell.

What’s more, it has proven effective for tumours as small as 1 mm in size, whereas calculations on ctDNA testing by the University of Toronto’s Eleftherios Diamandis have shown that tumours would need to be approximately 1 cm in diameter or greater to be detected. 

Already available as a so-called laboratory-based test in metropolitan Bangkok, X-ZELL Prostate™ will be subject to an international multi-centre trial in 2019 that could pave the way for a European market introduction in time for the next EPAD event in 2021.

Background

What does the current diagnostic pathway look like?

The current diagnostic standard for the early detection of prostate cancer is the Prostate Specific Antigen (PSA) test. While it has many limitations – as Richard J. Ablin, who discovered PSA in 1970, has vociferously argued on countless occasions – it is still the only solution that is both affordable and accessible at the same it. PSA testing typically serves as a tool to triage patients to prostate biopsy, a highly invasive procedure known for detecting a large portion of clinically insignificant cancers while missing clinically significant ones – all while exposing the patient to side-effects such as bleeding, pain, and infection. In a move to avoid such unnecessary interventions, multiparametric magnetic resonance imaging (mpMRI) has recently come into the spotlight as a potential pre-biopsy triage test. mpMRI is capable of detecting prostate lesions, classifying them on the basis of a five-point scoring system dubbed PI-RADS. PI-RADS scoring, however, is known to be subjective and does not distinguish clearly between intermediate and malignant cancer levels, often leading to differing interpretations among clinicians.

Why is prostate cancer such an urgent health issue?

According to the European Association of Urology (EAU), prostate cancer is the most commonly diagnosed cancer in European men, with more than 417,000 new cases and 92,000 deaths recorded each year. In 2018, the disease has overruled colorectal cancer as the second-most common cause of cancer-related death in men, only trailing behind lung cancer. Despite this significant public health burden, the Association continues to criticise how little action is taken to elevate it at EU level – particularly in comparison to breast, cervical and colorectal cancers.

Further reading: You can access the EAU’s full policy paper on PSA Screening here.