Dr Simon Crabb answers questions on prostate cancer

With more than 46,000 new cases diagnosed in the UK in 2014, prostate cancer is the most common cancer in men in the UK.  Whilst many men will survive their disease for ten years or more, there are still over 11,000 deaths from prostate cancer in the UK each year. The University of Southampton is leading on the development of treatments that harness the immune system to treat the more advanced forms of prostate cancer, with the potential to offer new hope to patients. Here we talk to Dr Simon Crabb, Associate Professor in Medical Oncology at the University of Southampton, who answers key questions on prostate cancer and explains more about the immunotherapy research taking place around prostate cancer in Southampton.

What is prostate cancer?

The prostate gland is about the size of a walnut and sits deep in the pelvis, just below the bladder, in men. It is important for reproduction because it makes semen. Cancer of the prostate occurs when the cells in the prostate gland grow and multiply in an abnormal way. The causes of this are complex but research is allowing us to understand the biology of the disease much better.

What is the current prognosis?

Overall, more than eight in ten (84 per cent) of men diagnosed with prostate cancer in the UK survive their disease for ten years or more. However, the outcomes are actually extremely variable depending on the specific circumstances that a particular man finds himself in. A proportion of men will never die, or indeed have any symptoms, from their prostate cancer. A further proportion of men can be cured with treatment to the prostate itself. However we still also have a little over 11,000 deaths from prostate cancer in the UK each year. The reasons for this wide spectrum of different outcomes, between prostate cancers that are not dangerous, through to those that are potentially lethal, is the focus of intense research activity. If we can understand this question better then we hope to be able to target treatment to those that require it, but spare it for men whose life is not at risk.

What treatment is usually recommended?

Because of the wide variation in outcomes and risk, there are a variety of options for treatment.  These fall into three broad categories. Firstly, for men with a potentially ‘safe’ cancer, it is often possible to undertake a process called ‘Active Surveillance’. This is a carefully controlled approach to monitoring a man who appears to have a low risk cancer, with the expectation that many will never need active treatment. In a second group of men, we offer treatments aimed at the prostate gland itself, using either surgery to remove it (a prostatectomy) or various types of radiotherapy. These treatments are undertaken to attempt to cure a prostate cancer that does represent a risk to a man’s life. Finally, there are a group of men who are diagnosed with, or subsequently develop, an incurable form of prostate cancer where the cancer has spread to distant parts of the body. The bones are the most common sites. In these circumstances we are able to use a variety of treatment options that include hormonal therapy, chemotherapy and radiation therapy. Although the cancer cannot be cured when there is distant spread in this way, these men live on average for about four to five years.

What research is currently taking place around prostate cancer treatments at the University of Southampton?

At the University of Southampton, we are involved in research into prostate cancer with a particular interest in developing novel treatment options. One strand of this research involves developing treatments to harness the immune system against prostate cancer. We have previously developed a vaccine against a protein called ‘prostate-specific membrane antigen’ (PSMA). PSMA is normally only produced by the prostate and prostate cancer cells. As a result the hope was to develop a vaccine that would target the immune system to attack prostate cancer. We completed an initial clinical trial, led by Professor Christian Ottensmeier, in which we were able to demonstrate that this did appear to be the case.

Our next approach will be to launch a clinical trial called POLERISE during 2017, which I will lead. In this trial we will use an experimental drug that we hope will be able to modify the interactions between the immune system and cells from the prostate cancer. Laboratory data suggests that these interactions are important in whether a prostate cancer responds to hormonal therapy. By targeting the immune system in this clinical trial we hope to remove a ‘break’ on the way the cancer responds to the hormonal therapy. This work on immunotherapy forms part of a wider program of work which I am leading on, looking at the development of new treatment options for prostate cancer.

What big breakthroughs have been made in cancer immunology relating to the treatment of prostate cancer and how is the University of Southampton involved? 

Prostate cancer was actually one of the very first cancers for which a treatment that utilised the immune system to attack a cancer was shown to work and enter mainstream use (in the USA). As an early breakthrough, this approach is considered as a proof of principle that prostate cancer interacts with the immune system and that we can target the immune system as a treatment strategy. This has led to clinical trials being led from Southampton, including the studies described above that look at the development of more sophisticated approaches to prostate cancer immunotherapy.

Do you believe that cancer immunotherapy has the potential to treat and cure prostate cancer?

We already have an established cancer immunotherapy treatment for advanced prostate cancer that is currently not curable and there is significant work ongoing both in Southampton and globally to take immunotherapy further in this disease. The ability to transfer these approaches through to use in patients that might potentially be cured is a high priority for future development.

What difference will the new Centre make to our research progress in this area?

The ability to develop new approaches for treatment of prostate cancer, and particularly immunotherapy strategies, will be greatly accelerated through the new Centre for Cancer Immunology at Southampton. By establishing this infrastructure we are able to bring together experts in prostate cancer drug development (led by myself) and cancer immunology (led by Professor Ottensmeier) with a team that are able to undertake the complex laboratory work that will be required. This is within a hub that has the clinical research infrastructure of the Southampton Clinical Trials Unit and the Southampton Experimental Cancer Medicine Centre to run complex early cancer trials.  If in these early trials the immunotherapy drugs are found to be promising, we can then develop a larger UK-wide clinical trial that could provide the evidence for immunotherapy to become standard treatment for future prostate cancer patients.