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Diagnosing Prostate Cancer: Challenges and Research

Every November marks Men’s Health Awareness Month, which shines the spotlight on this often overlooked area. Throughout this month, Cancer Research Wales will be publishing blogs on prostate cancer, which is the most common cancer in Wales and has a huge impact on thousands of men each year.

In this blog, we will discuss prostate cancer diagnosis. Finding out whether a patient has prostate cancer, and whether it is an aggressive form or not, remains challenging with a real lack of reliably accurate tests. However, research that Cancer Research Wales is funding is aiming to change that.

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Over 2500 men receive a prostate cancer diagnosis each year, but arriving at that diagnosis is often fraught with difficulties.

Prostate cancer usually grows very slowly, meaning that it can be present for years before symptoms become apparent. Even once symptoms (e.g. increased urgency of urinating) do begin, patients often associate them with simply getting older and so delay getting them checked by their GP. However, even once a patient does visit the GP that is only the beginning of the process for diagnosing prostate cancer.

Unlike some cancers, there is no single definitive test for prostate cancer – instead a combination of different techniques is typically used. The most common ones are discussed below.

When a patient first presents to the GP with symptoms, a physical examination is typically the first option. This takes the form of a digital rectal exam, where the doctor will put a finger into the patient’s rectum so that they can feel the prostate. In doing so, the doctor can feel for both the size and shape of the prostate, to determine whether it is enlarged or has any unusual lumps or bumps. Such changes may be indicative of prostate cancer, but are not sufficient on their own to give a diagnosis.

The PSA test measures the level of the protein PSA (Prostate-Specific Antigen) in a patient’s blood. PSA is produced by both healthy and cancerous cells in the prostate and released into the blood, where information about the prostate can be inferred from the amount of PSA that can be detected. The PSA level tends to increase when prostate cancer is present, because the prostate enlarges as the cancer grows. However, increased PSA levels can also be caused by non-cancerous conditions such as prostatitis or benign prostate hyperplasia, and PSA generally increases with age and even after vigorous exercise. Therefore, an elevated PSA level is not specific to prostate cancer and other tests are needed to confirm a diagnosis.

Where prostate cancer is suspected, patients are often referred for a biopsy. This involves using a needle to pierce the prostate and take a sample of the tissue, which can then be analysed in a laboratory. Typically, about 10 tissue samples are collected to increase the chance of detecting cancer – however, there is still a possibility that the needle might miss the cancer, especially if it is a small tumour. Furthermore, biopsies carry a risk of complications: the majority of men will develop an infection afterwards, which in a small number of cases can lead to sepsis; some men may experience bleeding, incontinence or impotence. Overall, this means that biopsies, while effective for diagnosing prostate cancer, can cause significant long-term harms so their use must be carefully weighed up with the patients.

In recent years there has been an increase in the use of multi-parametric Magnetic Resonance Imaging (mpMRI) scans for suspected prostate cancers. These are detailed MRI scans that produce images of the prostate which are interpreted by the medical team, to give them more information about what is happening in the prostate. mpMRI scans alone are not sufficient to diagnose prostate cancer, but the images can indicate whether a tumour is likely to be present and can act as a guide to improve the accuracy if a biopsy is needed.

While prostate cancer is often slow growing and so does not necessarily need immediate treatment, some patients have a more aggressive form which requires urgent treatment. The aforementioned tests that are used to detect prostate cancer are frequently unable to determine whether a patient has an aggressive or more indolent tumour, as well as not always providing a definitive diagnosis. This means that a significant number of patients are treated, enduring the associated side effects, when they should instead simply be monitored – this is known as ‘overtreatment’. Therefore, it would be a major boon for patients if a new test was available that could accurately detect prostate cancer and provide information about its aggressiveness to the clinicians.

Cancer Research Wales has for a number of years supported research into such a test, conducted by scientists in both Cardiff and Swansea and led by Dr Jason Webber. The team’s goal is to create a blood test for prostate cancer, that can also discriminate between aggressive and indolent tumours and so predict a patient’s prognosis.

Dr Webber’s team are interested in extracellular vesicles (EVs) – these are small bubbles which are released by most cells in the body. EVs act like shipping containers, transporting cargo which can be delivered to other cells around the body. This cargo varies depending on which cell type released the EV, and can be made up of various proteins, nucleic acids (such as RNA) and lipids. Previous research by the team showed that prostate cancer, particularly in its aggressive form, can cause changes to the tissue around the tumour. Their recent work has aimed to determine whether these changes lead to differences in the cargo of EVs released by the tissue and if so, whether the cancer-related cargo can be detected in the patient’s blood.

The first part of the current research analysed blood samples from prostate cancer patients, patients with benign prostatic hyperplasia (non-cancerous enlarged prostate) and healthy men. It was shown that EVs from prostate cancer patients had a number of RNA molecules in their cargo that were found at different levels compared to the other two groups. Subsequently, analysis of 80 prostate cancer patients (half with aggressive tumours and half less aggressive ones) was conducted and found that some of the candidate RNA molecules were found at different levels between the two groups i.e. could distinguish between the aggressive vs non-aggressive forms.

Currently, the team are using a second, larger cohort of prostate cancer patients to validate and confirm their findings. They are also exploring the possibility of enlisting machine learning techniques to improve the ability of their test to discriminate between different forms of prostate cancer.

While there is still a way to go before this new test is available to patients, the potential to give prostate cancer patients a swift and accurate diagnosis in a non-invasive manner is very exciting. With current tests offering a lack of accuracy and the risk of debilitating complications, as well leading to overtreatment of numerous men, the transformative potential of Dr Webber and his team’s research is clear.

The research discussed here represents one of several projects in our Early Diagnosis, Prevention and Screening research theme. If you’d like to learn more about our research, please visit the Our Research page here.