Time to Rethink Prostate Cancer Testing:
A Q&A With OBD’s CSO, Alexandre Akoulitchev, PhD, FRSM

Last updated: 09 November 2023

Prostate cancer awareness month

As November begins, we shift our focus to raising awareness about men’s health during Movember. We had a conversation with our Chief Scientific Officer, Dr. Alexandre Akoulitchev, about the importance of effective prostate cancer screening and his thoughts on the EpiSwitch PSE test. The test was launched in the US and UK in September 2023, coinciding with the end of Prostate Cancer Awareness Month.

Alexandre, a Fellow of the Royal Society of Medicine, co-founded Oxford BioDynamics (OBD) in 2007 and has been an inspirational leader, mentor, and researcher driving the company to the forefront of 3D genomics. Originally from Ukraine, Alexandre established OBD after his work at the Sir William Dunn School of Pathology, University of Oxford. Currently, he also serves as a Member of the National Institutes of Health (FNIH) Biomarker Steering Committees in Oncology, Neuroscience, and Immunology & Inflammation.

Q: One in eight men will experience prostate cancer in their lifetime. For black men, the risk is even higher, with rates as high as one in four. Notable figures like Robert De Niro, Ian McKellen, Ben Stiller, and Nelson Mandela have faced this diagnosis. Does this high occurrence influence your commitment to addressing this disease?

A: What many may not know is that prostate cancer ranks as the second most common cause of male cancer-related deaths.

If detected early while still localized, most men will survive a prostate cancer diagnosis for years. However, it's often diagnosed late due to the absence of noticeable symptoms. For men diagnosed with prostate cancer that has already spread to other parts of the body, the five-year survival rate drops to less than one in three.

Even when there's suspicion of prostate cancer, the current diagnostic tools available to doctors have limitations. They are often inaccurate and lack the sensitivity needed for precise diagnosis. The EpiSwitch PSE Test was designed to detect prostate cancer earlier with very high accuracy while reducing the number of men referred for unnecessary biopsies and treatment.

Q: How is prostate cancer currently diagnosed?

A: Despite its prevalence as the most common cancer in British men, testing for prostate cancer is far from perfect.

A PSA (Prostate-Specific Antigen) blood test may be an initial indication of prostate cancer, but it is so inaccurate that the NHS doesn't include PSA in any annual screening. A PSA test often suggests prostate cancer when no cancer exists (a false-positive). Around three in four men with an elevated PSA level will not have cancer, and approximately one in seven men with normal PSA levels may actually have prostate cancer (a false-negative), causing many cases to go undetected until it’s too late¹.

The definitive diagnosis for prostate cancer is a prostate biopsy, which involves using twelve needles to take random samples from the entire prostate. This procedure can lead to side effects like bleeding, infections, and erectile dysfunction. In the UK, nearly 120,000 men undergo this biopsy every year, with many of them being unnecessary due to the high false-positive rate of the PSA test².

Decades of using current testing regimes have raised valid concerns. Men are subjected to biopsies and treatment for prostate cancers that otherwise never would have been detected or caused harm. It's estimated that over 1,000 men need to be screened with the PSA test to prevent just one prostate cancer death³.

Healthcare providers may sometimes order additional tests before considering a biopsy. In the UK, an MRI might be used if localized prostate cancer is suspected. Although using MRI to screen men does avoid some biopsies, the positive predictive value (PPV) is still low, with one in two positive results being false (51% PPV)⁴, with evidence suggesting it may be lower in practice⁵. This approach can also be costly for healthcare providers.

Some groups are experimenting with methods that detect rare cell-free DNA in the blood, but their success in detecting prostate cancer has been limited. Indolent prostate cancer, in particular, releases less detectable DNA, making it challenging to identify early prostate cancers using this method, detecting only ~11% of early prostate cancers⁶.

You mentioned Ben Stiller earlier, who credits a PSA test with saving his life. While tests like the PSA can be helpful in specific cases, their limited accuracy has prevented the NHS from implementing a prostate cancer screening program in the UK. This is why we fast-tracked the development of the EpiSwitch PSE Test.

Q: There was massive media interest following your publication of data from a clinical study showing the potential of EpiSwitch PSE as an accurate and rapid cancer screening diagnostic. What can we expect?

A: In September 2023, we successfully launched EpiSwitch PSE in the US and UK. This PSE test is a powerful tool for assessing an individual's risk of prostate cancer using a simple blood test. It enhances the accuracy of standard PSA tests and offers clear guidance to healthcare providers, helping them decide whether a biopsy is necessary or if active surveillance suffices. It's worth noting that PSE underwent rigorous validation with the Imperial NHS Trust, involving a significant group of asymptomatic men randomly invited for cancer screening.

We anticipate that the PSE test will bring about two significant changes.

First, it has the potential to significantly reduce the number of men who are unnecessarily referred for diagnostic biopsies or treatment. The PSE boasts an impressive PPV, with an estimated 13 out of 14 men receiving a "High Probability" PSE result likely to be diagnosed with cancer. This could spare many men from unnecessary biopsies and overtreatment, ultimately conserving healthcare resources for more effective allocation in the fight against the disease.

Second, the PSE test is expected to enhance the early detection of prostate cancer, increasing the chances of timely treatment, especially when more treatment options are available. The PSE test substantially improves sensitivity, raising it from the PSA test's 33% (based on results from the PROSTAGRAM study⁵) to approximately 86%. When considering all the advantages the PSE offers, we believe it could drive the widespread adoption of prostate screening and lead to the early detection of more prostate cancers.

Q: What aspect of Oxford BioDynamics' future are you most enthusiastic about?

A: We've built a expertly curated 3D genome knowledgebase with immense untapped potential. It contains over 800 million data points derived from 15,000+ samples across 30+ human diseases. Through over 40 collaborations with prominent pharmaceutical companies and leading academic institutions, we've successfully translated this knowledge into practical clinical applications using our proprietary EpiSwitch technology.

I am immensely proud of our contributions to immuno-oncology, particularly with the successful adoption and expert support for our EpiSwitch CiRT test. This test aids in predicting patient responses to immune checkpoint inhibitors based on a quick blood readout. As a CLIA lab test, CiRT greatly assists clinicians, patients, and health insurers in navigating the complexities of immunotherapy practice, which involves an annual expenditure of over $40 billion on checkpoint inhibitor drugs alone.

I'm equally proud of the outstanding performance demonstrated by our EpiSwitch PSE prostate screening test in the extensive PROSTAGRAM trial conducted by Imperial NHS Trust⁵. In the UK, approximately 10 million men between the ages of 50 and 74 could benefit from the PSE test, while in the US, the number is close to 50 million.

As previously mentioned, our upcoming commercial tests include early detection of colorectal cancer and, in the field of veterinary medicine, a multi-choice early diagnostic test for the most prevalent dog cancers. The latter holds a special place in my heart as it allows us to apply our technology to assist our beloved canine companions. Additionally, it sets the stage for developing a human version of a high-performance multi-choice early cancer detection test.

Leveraging the power and capabilities of EpiSwitch biomarker technology, OBD is actively pursuing opportunities to provide individuals with the confidence to face the most challenging health decisions. We're also assisting healthcare institutions in making informed choices and supporting more effective treatment regimens.

References

1) NHS PSA testing https://www.nhs.uk/conditions/prostate-cancer/psa-testing/'>

2) BBC News (2017) https://www.bbc.co.uk/news/health-38665618

3) Harvard Health Publishing (2020), Time to rethink the debate on PSA testing. https://www.health.harvard.edu/blog/time-to-rethink-the-psa-to-test-or-not-to-test-debate-2017092912463

4) Ahmed et al., Lancet (2017) https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)32401-1/fulltext

5) Dmitri Pchejetski et al., Cancers (2023) https://www.mdpi.com/2072-6694/15/3/821

6) *Klein EA, Richards D, et al. Clinical validation of a targeted methylation-based multi-cancer early detection test using an independent validation set. Ann Oncol. 2021 Sep;32(9):1167-1177. doi: https://doi.org/10.1016/j.annonc.2021.05.806