Smarter identification and management of Early prostate cancer: improving Lives and outcomEs through Clinical Translation of novel magnetic resonance imaging (SELeCT)

Fundamental challenges remain with the diagnosis and management of prostate cancer: (i) deaths from PCa continue to rise (approx. >12,000 deaths per year in the UK); suggesting that we are not capturing the right men for treatment early enough with our current approach of waiting for men to themselves present for testing; (ii) currently 1 in 2 men with a positive MRI do not have significant cancer when a biopsy is performed; these 'false positive' MRI tests create an unnecessary drain on NHS resources and negatively impact men being investigated for PCa (approx. 100,000 biopsies per year in the UK; estimated 50% unnecessary); (iii) whilst early diagnosis of prostate cancer is welcome, it is likely to result in overtreatment of the disease with inherent side effects as there is no reliable method to accurately predict if a man diagnosed with early prostate cancer has an aggressive (that will likely lead to death) or an indolent (where treatment can be safely avoided) cancer (approx. 5000 prostatectomies for localised disease per year in the UK, estimated 40% as 'overtreatment') We have been developing three such MRI methods with a specific focus on solving the above challenges: Luminal water imaging (LWI) The normal prostate consists of a glandular lumen (containing secretions) and cellular areas.

Clinically significant (cancer alters the balance of glandular to cellular space, reducing the fraction of glandular lumen.

This fraction decreases as the grade of the tumour increases [the higher the grade, the more likely the tumour needs treating].

LWI uses a standard method (available on any clinical MRI scanner) in a novel way in order to create images that reflect the fraction of glandular lumen within each pixel, thereby allowing of significant prostate cancer.

It requires around 7-10 minutes of scanning time (compared with conventional MRI of 30-45 minutes), and because of its simplicity, it might be able to be applied in asymptomatic men in the general population as a method for screening for prostate cancer.

Vascular, Extracellular, and Restricted Diffusion for Cytometry in Tumours (VERDICT) MRI, is a more complex MRI method that has to be specifically programmed and can currently be performed on high-end clinical MRI scanners. We have shown that it can interrogate the microstructure of tissue within each pixel more precisely than other methods.

It has the potential to be used together with standard MRI to avoid unnecessary biopsies in patients where the normal MRI shows a lesion that needs biopsy. 13C-Pyruvate hyperpolarised MRI allows assessment of the metabolism of cancer. The technology is installed in a handful of expert centres in the UK.

Using this technique for the first time, we have an opportunity to try and differentiate tumours with high metabolism which are known to be more aggressive.

With development this method might help patients with less aggressive, low-metabolism tumours avoid unnecessary treatments.

This application will bring these technologies into clinical use (through translational and clinical efficacy studies), and improve the lives and outcomes of men being investigated and treated for prostate cancer.