Funding promising research into prostate cancer

One in six men will be diagnosed with prostate cancer in their lifetime, yet only a small fraction will face a lethal outcome. Over 20 years ago, this paradox prompted UK surgeons to initiate ProtecT, one of the boldest clinical trials in history. One thousand, six hundred and forty-three men with localised prostate cancer and a life expectancy of at least ten years were randomly assigned to surgery, radiotherapy, or active monitoring. Fifteen years later, the results were striking: only 45 men (2.7 per cent) had died from prostate cancer, with no significant differences between the treatment groups.

These findings can be distilled into two key points. Most men with localised prostate cancer can live long lives without receiving debilitating treatment. Yet a small group of men with aggressive, undetected disease could not be cured, however early they were treated. Understanding which prostate cancers are lethal and how to spot them early enough to give these men hope of a cure is therefore a key research question in the field.

This is where my research steps in, with its aim once aptly described by The Sunday Times as ‘distinguishing tigers from pussycats’. How am I hoping to achieve this as an academic radiologist? First, by taking a step back from the grayscale world of MRI and looking at the tumours of ProtecT participants under the microscope. By doing so, we can try to differentiate lesions that metastasised and became incurable from those that remained localised or were effectively treated. Early analysis is promising, with the full results expected by the end of summer. Since half of the ProtecT biopsies are stored in Oxford, the mutual agreement between Emmanuel and Exeter colleges has been key to enabling me to complete this crucial work as a Visiting Fellow of our sister college.

If our preliminary results are confirmed, will it make a difference to patients? It appears that most ‘tigers’ from ProtecT come in the shape of sieve-like tumours. In contemporary clinical guidelines, these lesions are considered intermediate-risk, which means that a lot of men with this type of cancer are still offered active surveillance instead of upfront treatment. Demonstrating their increased aggressiveness in a randomised controlled trial such as ProtecT could therefore lead to revisiting the current approach to risk stratification. Practically, as more patients with sieve-like disease would be treated, more patients with other types of intermediate risk prostate cancer could be more confident about delaying their treatment.

The trouble is that sieve-like disease is notoriously difficult to detect with routinely used diagnostic approaches. In particular MRI, which is now offered to all patients with suspected prostate cancer thanks to revolutionary research done in the UK, can misdiagnose up to one-third of sieve-like lesions. This is because standard MRI is designed to detect all prostate cancers, rather than to separate them into specific subtypes. So how do we know which technique to use?

The rapidly expanding Cambridge Biomedical Campus offers unparalleled opportunities for collaboration between academics, clinicians and industry. In close partnership with researchers from AstraZeneca, we have identified specific biomarkers of sieve-like disease that can both explain its aggressiveness and also be used for diagnostic purposes. We now have pilot clinical data suggesting that a certain type of PET scan is superior to standard MRI for accurately identifying sieve-like lesions. Over the remainder of my Research Fellowship, I hope to publish these pieces of evidence and put together funding proposals for clinical trials that can prove the ability of new imaging techniques to detect sieve like disease early and thereby improve the prognosis for patients harbouring it.

For clinicians, full-time research is a luxury. The Research Fellowship at Emmanuel has offered me a unique opportunity to focus on the work that I believe can make a real clinical and academic impact. College life also exposes one to ideas of others, which are a great source of inspiration. I was therefore pleased to be involved in reviving the Thomas Young Club, which is now an after-dinner discussion club in which Fellows and students come together to discuss ideas behind research. After all, as Karl Popper said, we are not students of subjects, but students of problems. And as problems often transcend disciplinary boundaries, solving the grayscale mysteries of MRI sometimes requires a closer look through a microscope.

Nikita Sushentsev, Emmanuel Review (2024)